Comprehension of the zinc chloride's ameliorative apoptotic and genotoxic effects on mice with cadmium-induced hepatotoxicity

Cadmium is a typical heavy metal quite dangerous to humans and animals. Zinc supplementation protects the biological system from Cd toxicity and alleviates Cd-induced toxicity. The present study was assessed to evaluate the preventive effects of zinc chloride (ZnCl2) on male mice with liver damage induced by cadmium chloride (CdCl2). Metals accumulation was quantified in the liver. Body weight, liver weight ratio, lipid peroxidation, caspase 3, and DNA damage were determined in the liver of male mice after receiving an intraperitoneal (IP) a single dose of CdCl2 at 1.5 and 3 mg/kg or/and ZnCl2 10 mg/kg during 21 days. The LD50 was 6.023 mg/kg for CdCl2 and 89.05 mg/kg for ZnCl2. The results indicate that mice in control and Zn groups gained body weight at the end of the experiment, while other treated groups significantly decreased. The relative weight of the liver revealed a significant increase in experimental groups. In addition, an increase in malondialdehyde level, Metallothionein concentration, and caspase-3 level was detected in Cd and Zn groups alone or in combination. Strand breaks of DNA of hepatocytes showed a significant increase in tail length of groups treated with cadmium. Co-treatment with zinc reduced these parameters compared to those measured in cells treated with cadmium. The outcome of this study implied that cadmium chloride causes oxidative stress, DNA damage, and elevated apoptosis markers in mice livers at low and medium doses. By pinpointing the target organ involved, the study results have also added some understanding of the impacts of zinc chloride injection to ameliorate cadmium toxicity in a low dose at 10 mg/kg.

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle

ABSTRACT: This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.

RESUMO: Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.

Spontaneous poisoning by Cestrum intermedium in dairy cattle

ABSTRACT: Acute hepatotoxicity caused by plants poisoning is responsible for economic losses in farm animals in Brazil. Reports of Cestrum intermedium natural poisoning in cattle are not commonly described in Rio Grande do Sul (RS). This study aimed to document an outbreak of spontaneous C. intermedium poisoning in dairy cattle in the Central-Eastern Mesoregion of RS. Three nine-month-old Holstein and Jersey heifers were affected after they were placed in a small paddock with shortage forage. In this area, specimens of C. intermedium Sendtn with signs of consumption were observed. Morbidity and lethality rates were 100% and clinical courses ranged from 9 to 12 hours. At post mortem examination of the three heifers, there was predominance of acute liver lesions. The liver was moderately enlarged and on the cut surface there was a marked accentuation of the lobular pattern and hemorrhage. Inside the rumen, partially digested C. intermedium Sendtn leaves were observed. The histological aspects of the liver were mostly centrilobular coagulative necrosis and hemorrhage, frequently extended to the midzonal region. The immunohistochemistry technique was performed, in which the polyclonal antibody caspase 3 was used in liver fragments. Moderate to marked immunolabeling was observed in the cytoplasm and nucleus of hepatocytes, predominantly on the periphery of areas of hepatic necrosis indicating cell apoptosis. The diagnosis of C. intermedium Sendtn poisoning in dairy cattle in this study was based on epidemiological, clinical and anatomopathological findings. Since the C. intermedium poisoning is uncommon in dairy cattle, we are describing it for the first time in the Central-Eastern Mesoregion of RS, and represents a differential diagnosis of other acute toxic liver diseases in cattle.

RESUMO: Intoxicações por plantas que causam hepatotoxicidade aguda são responsáveis por prejuízos econômicos em animais de produção no Brasil. Relatos de intoxicações naturais por Cestrum intermedium em bovinos não são comumente descritos no Rio Grande do Sul (RS). Este trabalho teve como objetivo documentar um surto de intoxicação espontânea por C. intermedium em bovinos leiteiros ocorrido na região Centro-Oriental do RS. Três bovinos com nove meses de idade, das raças Holandês e Jersey, foram acometidos depois de serem introduzidos em um pequeno piquete com escassez de forragem. Nessa área foram observados exemplares de Cestrum intermedium Sendtn com sinais de consumo. As taxas de morbidade e letalidade foram de 100% e os cursos clínicos variaram de 9 a 12 horas. Na necropsia dos três bovinos, observou-se predomínio de lesões hepáticas agudas. O fígado dos animais acometidos estava moderadamente aumentado de tamanho e na superfície de corte havia marcada acentuação do padrão lobular e hemorragia. Na abertura do rúmen, foram observadas folhas de Cestrum intermedium Sendtn parcialmente digeridas. Histologicamente, o fígado apresentava necrose coagulativa centrolobular e hemorragia. Frequentemente, essas alterações se estendiam para a região mediozonal. Foi realizada a técnica de imuno-histoquímica, na qual utilizou-se o anticorpo policlonal caspase 3 em fragmentos de fígado. Notou-se marcação moderada a acentuada em citoplasma e núcleo de hepatócitos, predominantemente na periferia das áreas de necrose hepática indicando apoptose celular. O diagnóstico de intoxicação por Cestrum intermedium Sendtn nos bovinos leiteiros desse estudo, foi realizado com base nos achados epidemiológicos, clínicos e anatomopatológicos. A intoxicação por C. intermedium é incomum em bovinos leiteiros, sendo descrita pela primeira vez na região centro oriental do RS e representa um diagnóstico diferencial de outras hepatopatias tóxicas agudas.

Spontaneous poisoning by Dodonaea viscosa (Sapindaceae) in cattle in Southern Brazil

ABSTRACT: In this study, an outbreak of spontaneous poisoning by Dodonaea viscosa (D. viscosa) in a herd of dairy cattle in the municipality of Capão do Leão, Rio Grande do Sul, was investigated. Three deaths occurred in a batch of 16 Jersey cattle, aged between three and four years, kept in a native field. The clinical signs observed were apathy, decreased production, and anorexia, with death occurring within approximately 48 h after the onset of signs. The three cattle were necropsied, and tissue samples were sent for histopathological examination. Necropsy findings included serosanguineous fluid in the abdominal cavity, intestines with congested serosa, and marked mesenteric edema. The mucosa of the abomasum of two of the animals was hemorrhagic with bloody content, and among the ruminal content of a bovine, leaves with morphological characteristics compatible with D. viscosa were observed. The livers of the three animals were enlarged, with accentuation of the lobular pattern. Histologically, centrilobular coagulation necrosis with congestion and hemorrhage was observed in the liver. Vacuolization and degeneration of hepatocytes were observed in the mid-zonal and periportal regions. The diagnosis of poisoning by D. viscosa leaves was based on epidemiological data, necropsy findings, and histopathological alterations. The presence of the plant in the rumen and in the grazing site of the affected cattle was essential for the diagnosis.

RESUMO: Neste trabalho, é descrito um surto de intoxicação espontânea por Dodonaea viscosa (D. viscosa) ocorrido em um rebanho de bovinos leiteiros, no município de Capão do Leão, no Rio Grande do Sul. Ocorreram três mortes em um lote de 16 bovinos da raça Jersey com idades entre três e quatro anos, mantidos em campo nativo. Os sinais clínicos observados foram apatia, queda na produção e anorexia, com morte em aproximadamente 48 horas após o início dos sinais. Os três bovinos foram necropsiados, e amostras de tecidos foram encaminhadas para exame histopatológico. Os achados de necropsia incluíam líquido serossanguinolento na cavidade abdominal, intestinos com serosas congestas e marcado edema de mesentério. A mucosa do abomaso de dois animais apresentava-se hemorrágica com conteúdo sanguinolento e, em meio ao conteúdo ruminal de um bovino foram observadas folhas com caracteres morfológicos compatíveis com D. viscosa. O fígado dos três animais estava aumentado, com acentuação do padrão lobular. Histologicamente no fígado havia necrose de coagulação centrolobular com congestão e hemorragia. Nas regiões médio-zonal e periportal observou-se vacuolização e degeneração dos hepatócitos. O diagnóstico de intoxicação pelas folhas D. viscosa foi baseado nos dados epidemiológicos, nos achados de necropsia e nas alterações histopatológicas. A presença da planta no rúmen e no local de pastoreio dos bovinos afetados foi fundamental para o diagnóstico.

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle / Hepatotoxicidade necrótica aguda por ingestão de Lantana camara L. em bovinos leiteiros

This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.(AU)

Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.(AU)

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle / Hepatotoxicidade necrótica aguda por ingestão de Lantana camara L. em bovinos leiteiros

This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.(AU)

Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.(AU)

Evaluation of potential hepatotoxicity induced by Bortezomib

Bortezomib, an inhibitor of 26S proteasome, is an anti-cancer therapeutic agent used in different cancer types. It leads to the arrest of the cancerous cell cycle by inhibiting angiogenesis and inducing apoptosis. Liver is the vital organ for detoxification and excretion of toxic products. The treatment with chemotherapy is a challenge, drugs are used to destroy cancer cells, but healthy cells can be affected during cancer treatment as well. The main objective of this study was to analyze the histopathological and biochemical effects of bortezomib on liver. Twenty-four female C57BL/6 mice were distributed into 4 groups, bortezomib injected treatment groups (Btz1, Btz2) and saline injected control groups (C1, C2). Bortezomib and saline were treated twice per week for 6 weeks and sacrificed at the end of one day (Btz1, C1) and 4 weeks (Btz2, C2) after the last injection. Liver samples were examined for histopathological analysis and the serum samples processed for biochemical analysis. Tissue samples were fixed, routinely processed, sectioned, and stained with Hematoxylin and Eosin (H&E). Periodic Acid-Schiff (PAS), Sudan Black staining and Masson's trichrome histochemical staining methods were performed to characterize the lesions. Histopathological analysis of the Btz1 and Btz2 groups revealed acute hepatic morphological changes such as hepatocellular swelling (cloudy swelling), necro-inflammatory reaction, and increased mononuclear polyploidy. Based on the negative staining with PAS and Sudan Black staining, hepatocellular swelling was diagnosed as hydropic degeneration. Necro-inflammatory reaction observed in the form of acute hepatitis was composed of mainly mononuclear cell infiltration accompanied by multifocal necrotic foci. Kupffer cell proliferation was observed in parallel with degenerative and necrotic changes. An Increase in hepatocellular mononuclear polyploidy visualized as hepatocytes with a single enlarged nucleus was detected in all liver sections of Btz1 and Btz2 groups. Individual cases of cholestasis (n = 1) and mild hepatic fibrosis (n = 1) were also reported. Significant elevated levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were detected in bortezomib treated groups. Few clinical cases reported liver injury related to bortezomib used for cancer treatment. However, the liver was not considered as a target for bortezomib treatment. Our data suggesting that bortezomib caused liver damage and induces elevations in serum levels. The reported hepatic lesions including hepatocellular swelling, acute hepatitis and mononuclear polyploidy were mainly mild and moderate in severity. The increase of polyploidy in liver tissue of mice treated with bortezomib in this study was explained as a reaction of the liver facing the drug-induced hepatic damage. The mechanism leading to the hepatotoxicity of bortezomib treatment is not known but the production of a toxic metabolite through its metabolism in the liver can be suggested. Moreover, no recovery was also observed in histopathological and biochemical analyses suggesting that the bortezomib effect is non-reversible four weeks after the drug was withdrawn. Patients should be informed about the possibility of acute drug-induced hepatitis and hepatotoxicity of this chemotherapeutic agent after the treatment.(AU)

Spontaneous poisoning by Cestrum intermedium in dairy cattle / Intoxicação espontânea por Cestrum intermedium em bovinos de leite

Acute hepatotoxicity caused by plants poisoning is responsible for economic losses in farm animals in Brazil. Reports of Cestrum intermedium natural poisoning in cattle are not commonly described in Rio Grande do Sul (RS). This study aimed to document an outbreak of spontaneous C. intermedium poisoning in dairy cattle in the Central-Eastern Mesoregion of RS. Three nine-month-old Holstein and Jersey heifers were affected after they were placed in a small paddock with shortage forage. In this area, specimens of C. intermedium Sendtn with signs of consumption were observed. Morbidity and lethality rates were 100% and clinical courses ranged from 9 to 12 hours. At post mortem examination of the three heifers, there was predominance of acute liver lesions. The liver was moderately enlarged and on the cut surface there was a marked accentuation of the lobular pattern and hemorrhage. Inside the rumen, partially digested C. intermedium Sendtn leaves were observed. The histological aspects of the liver were mostly centrilobular coagulative necrosis and hemorrhage, frequently extended to the midzonal region. The immunohistochemistry technique was performed, in which the polyclonal antibody caspase 3 was used in liver fragments. Moderate to marked immunolabeling was observed in the cytoplasm and nucleus of hepatocytes, predominantly on the periphery of areas of hepatic necrosis indicating cell apoptosis. The diagnosis of C. intermedium Sendtn poisoning in dairy cattle in this study was based on epidemiological, clinical and anatomopathological findings. Since the C. intermedium poisoning is uncommon in dairy cattle, we are describing it for the first time in the Central-Eastern Mesoregion of RS, and represents a differential diagnosis of other acute toxic liver diseases in cattle.(AU)

Intoxicações por plantas que causam hepatotoxicidade aguda são responsáveis por prejuízos econômicos em animais de produção no Brasil. Relatos de intoxicações naturais por Cestrum intermedium em bovinos não são comumente descritos no Rio Grande do Sul (RS). Este trabalho teve como objetivo documentar um surto de intoxicação espontânea por C. intermedium em bovinos leiteiros ocorrido na região Centro-Oriental do RS. Três bovinos com nove meses de idade, das raças Holandês e Jersey, foram acometidos depois de serem introduzidos em um pequeno piquete com escassez de forragem. Nessa área foram observados exemplares de Cestrum intermedium Sendtn com sinais de consumo. As taxas de morbidade e letalidade foram de 100% e os cursos clínicos variaram de 9 a 12 horas. Na necropsia dos três bovinos, observou-se predomínio de lesões hepáticas agudas. O fígado dos animais acometidos estava moderadamente aumentado de tamanho e na superfície de corte havia marcada acentuação do padrão lobular e hemorragia. Na abertura do rúmen, foram observadas folhas de Cestrum intermedium Sendtn parcialmente digeridas. Histologicamente, o fígado apresentava necrose coagulativa centrolobular e hemorragia. Frequentemente, essas alterações se estendiam para a região mediozonal. Foi realizada a técnica de imuno-histoquímica, na qual utilizou-se o anticorpo policlonal caspase 3 em fragmentos de fígado. Notou-se marcação moderada a acentuada em citoplasma e núcleo de hepatócitos, predominantemente na periferia das áreas de necrose hepática indicando apoptose celular. O diagnóstico de intoxicação por Cestrum intermedium Sendtn nos bovinos leiteiros desse estudo, foi realizado com base nos achados epidemiológicos, clínicos e anatomopatológicos. A intoxicação por C. intermedium é incomum em bovinos leiteiros, sendo descrita pela primeira vez na região centro oriental do RS e representa um diagnóstico diferencial de outras hepatopatias tóxicas agudas.(AU)

Spontaneous poisoning by Cestrum intermedium in dairy cattle / Intoxicação espontânea por Cestrum intermedium em bovinos de leite

Acute hepatotoxicity caused by plants poisoning is responsible for economic losses in farm animals in Brazil. Reports of Cestrum intermedium natural poisoning in cattle are not commonly described in Rio Grande do Sul (RS). This study aimed to document an outbreak of spontaneous C. intermedium poisoning in dairy cattle in the Central-Eastern Mesoregion of RS. Three nine-month-old Holstein and Jersey heifers were affected after they were placed in a small paddock with shortage forage. In this area, specimens of C. intermedium Sendtn with signs of consumption were observed. Morbidity and lethality rates were 100% and clinical courses ranged from 9 to 12 hours. At post mortem examination of the three heifers, there was predominance of acute liver lesions. The liver was moderately enlarged and on the cut surface there was a marked accentuation of the lobular pattern and hemorrhage. Inside the rumen, partially digested C. intermedium Sendtn leaves were observed. The histological aspects of the liver were mostly centrilobular coagulative necrosis and hemorrhage, frequently extended to the midzonal region. The immunohistochemistry technique was performed, in which the polyclonal antibody caspase 3 was used in liver fragments. Moderate to marked immunolabeling was observed in the cytoplasm and nucleus of hepatocytes, predominantly on the periphery of areas of hepatic necrosis indicating cell apoptosis. The diagnosis of C. intermedium Sendtn poisoning in dairy cattle in this study was based on epidemiological, clinical and anatomopathological findings. Since the C. intermedium poisoning is uncommon in dairy cattle, we are describing it for the first time in the Central-Eastern Mesoregion of RS, and represents a differential diagnosis of other acute toxic liver diseases in cattle.(AU)

Intoxicações por plantas que causam hepatotoxicidade aguda são responsáveis por prejuízos econômicos em animais de produção no Brasil. Relatos de intoxicações naturais por Cestrum intermedium em bovinos não são comumente descritos no Rio Grande do Sul (RS). Este trabalho teve como objetivo documentar um surto de intoxicação espontânea por C. intermedium em bovinos leiteiros ocorrido na região Centro-Oriental do RS. Três bovinos com nove meses de idade, das raças Holandês e Jersey, foram acometidos depois de serem introduzidos em um pequeno piquete com escassez de forragem. Nessa área foram observados exemplares de Cestrum intermedium Sendtn com sinais de consumo. As taxas de morbidade e letalidade foram de 100% e os cursos clínicos variaram de 9 a 12 horas. Na necropsia dos três bovinos, observou-se predomínio de lesões hepáticas agudas. O fígado dos animais acometidos estava moderadamente aumentado de tamanho e na superfície de corte havia marcada acentuação do padrão lobular e hemorragia. Na abertura do rúmen, foram observadas folhas de Cestrum intermedium Sendtn parcialmente digeridas. Histologicamente, o fígado apresentava necrose coagulativa centrolobular e hemorragia. Frequentemente, essas alterações se estendiam para a região mediozonal. Foi realizada a técnica de imuno-histoquímica, na qual utilizou-se o anticorpo policlonal caspase 3 em fragmentos de fígado. Notou-se marcação moderada a acentuada em citoplasma e núcleo de hepatócitos, predominantemente na periferia das áreas de necrose hepática indicando apoptose celular. O diagnóstico de intoxicação por Cestrum intermedium Sendtn nos bovinos leiteiros desse estudo, foi realizado com base nos achados epidemiológicos, clínicos e anatomopatológicos. A intoxicação por C. intermedium é incomum em bovinos leiteiros, sendo descrita pela primeira vez na região centro oriental do RS e representa um diagnóstico diferencial de outras hepatopatias tóxicas agudas.(AU)

Clinical safety of zafirlukast treatment during acute inflammatory reaction in nile tilapia (Oreochromis niloticus) / Segurança clínica do tratamento com zafirlucaste durante a reação inflamatória aguda em tilápia do nilo (Oreochromis niloticus)

Little is known about the toxicity of immune modulators in fish. Zafirlukast is an anti-inflammatory that antagonizes cysteine leukotriene receptors (CysLTR1). Aiming to study immunomodulatory treatments on fish health, this study evaluated the clinical safety of oral zafirlukast treatment, through biochemical and hematological analyzes during acute inflammatory reaction in Nile tilapia (Oreochromis niloticus), induced by Aeromonas hydrophila bacterins. 72 young tilapias were randomly divided in 9 aquariums (100 L each, n=8) to compose the following treatments: T0 (control), T1 (Treatment with 250 µg zafirlukast) and T2 (Treatment with 500 µg zafirlukast). Eight animals were evaluated per treatment in three periods: six, 24 and 48 hours post-inoculation (HPI), blood collection was performed for hematological and serum biochemical evaluation. The study of hepatic and renal functionality revealed that treatment with both doses of zafirlukast did not result in changes in the circulating values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, creatinine, triglycerides, cholesterol, and total protein, suggesting that the drug has not presented hepatotoxicity, as well as compromised liver and kidney functions. Tilapia submitted to treatment with 500 µg showed adverse hematological effects characterized by polycythemia associated with microcytosis. Therefore, oral treatment with zafirlukast has demonstrated clinical safety at a therapeutic dose of 250 µg in tilapia during acute aerocystitis, although hematological changes were observed in tilapia treated with overdose of this leukotriene blocker

Pouco se sabe sobre a toxicidade de imunomoduladores em peixes. Zafirlukast é um anti-inflamatório que antagoniza os receptores de leucotrienos cisteínicos (CysLTR1). Com o objetivo de estudar o efeito de tratamentos imunomoduladores sobre a saúde dos peixes, este estudo avaliou a segurança clínica do tratamento com zafirlucaste oral, por meio de análises bioquímicas e hematológicas durante reação inflamatória aguda em tilápia do Nilo (Oreochromis niloticus), induzida por bacterinas de Aeromonas hydrophila. Para tal, 72 tilápias jovens foram divididas aleatoriamente em 9 aquários (100 L cada, n=8) para compor os seguintes tratamentos: T0 (controle), T1 (Tratamento com 250 µg de zafirlucaste) e T2 (Tratamento com 500 µg de zafirlucaste). Oito animais foram avaliados por tratamento em três períodos: seis, 24 e 48 horas pós-inoculação (HPI), foi realizada coleta de sangue para avaliação hematológica e bioquímica sérica. O estudo da funcionalidade hepática e renal revelou que o tratamento com ambas as doses de zafirlucaste não resultou em alterações nos valores circulantes de aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina, creatinina, triglicerídeos, colesterol e proteína total, sugerindo que a droga não comprometeu as funções hepáticas e renais. As tilápias tratadas com 500 µg apresentaram efeitos hematológicos adversos caracterizados por policitemia associada a microcitose. Portanto, o tratamento oral com zafirlucaste demonstrou segurança clínica na dose de 250 µg em tilápias durante aerocistite aguda, embora alterações hematológicas tenham sido observadas em tilápias tratadas com sobredosagem deste bloqueador de leucotrieno.

Spontaneous poisoning by Dodonaea viscosa (Sapindaceae) in cattle in Southern Brazil / Intoxicação espontânea por Dodonaea viscosa (Sapindaceae) em bovinos no sul do Brasil

In this study, an outbreak of spontaneous poisoning by Dodonaea viscosa (D. viscosa) in a herd of dairy cattle in the municipality of Capão do Leão, Rio Grande do Sul, was investigated. Three deaths occurred in a batch of 16 Jersey cattle, aged between three and four years, kept in a native field. The clinical signs observed were apathy, decreased production, and anorexia, with death occurring within approximately 48 h after the onset of signs. The three cattle were necropsied, and tissue samples were sent for histopathological examination. Necropsy findings included serosanguineous fluid in the abdominal cavity, intestines with congested serosa, and marked mesenteric edema. The mucosa of the abomasum of two of the animals was hemorrhagic with bloody content, and among the ruminal content of a bovine, leaves with morphological characteristics compatible with D. viscosa were observed. The livers of the three animals were enlarged, with accentuation of the lobular pattern. Histologically, centrilobular coagulation necrosis with congestion and hemorrhage was observed in the liver. Vacuolization and degeneration of hepatocytes were observed in the mid-zonal and periportal regions. The diagnosis of poisoning by D. viscosa leaves was based on epidemiological data, necropsy findings, and histopathological alterations. The presence of the plant in the rumen and in the grazing site of the affected cattle was essential for the diagnosis.(AU)

Neste trabalho, é descrito um surto de intoxicação espontânea por Dodonaea viscosa (D. viscosa) ocorrido em um rebanho de bovinos leiteiros, no município de Capão do Leão, no Rio Grande do Sul. Ocorreram três mortes em um lote de 16 bovinos da raça Jersey com idades entre três e quatro anos, mantidos em campo nativo. Os sinais clínicos observados foram apatia, queda na produção e anorexia, com morte em aproximadamente 48 horas após o início dos sinais. Os três bovinos foram necropsiados, e amostras de tecidos foram encaminhadas para exame histopatológico. Os achados de necropsia incluíam líquido serossanguinolento na cavidade abdominal, intestinos com serosas congestas e marcado edema de mesentério. A mucosa do abomaso de dois animais apresentava-se hemorrágica com conteúdo sanguinolento e, em meio ao conteúdo ruminal de um bovino foram observadas folhas com caracteres morfológicos compatíveis com D. viscosa. O fígado dos três animais estava aumentado, com acentuação do padrão lobular. Histologicamente no fígado havia necrose de coagulação centrolobular com congestão e hemorragia. Nas regiões médio-zonal e periportal observou-se vacuolização e degeneração dos hepatócitos. O diagnóstico de intoxicação pelas folhas D. viscosa foi baseado nos dados epidemiológicos, nos achados de necropsia e nas alterações histopatológicas. A presença da planta no rúmen e no local de pastoreio dos bovinos afetados foi fundamental para o diagnóstico.(AU)

Spontaneous poisoning by Dodonaea viscosa (Sapindaceae) in cattle in Southern Brazil / Intoxicação espontânea por Dodonaea viscosa (Sapindaceae) em bovinos no sul do Brasil

In this study, an outbreak of spontaneous poisoning by Dodonaea viscosa (D. viscosa) in a herd of dairy cattle in the municipality of Capão do Leão, Rio Grande do Sul, was investigated. Three deaths occurred in a batch of 16 Jersey cattle, aged between three and four years, kept in a native field. The clinical signs observed were apathy, decreased production, and anorexia, with death occurring within approximately 48 h after the onset of signs. The three cattle were necropsied, and tissue samples were sent for histopathological examination. Necropsy findings included serosanguineous fluid in the abdominal cavity, intestines with congested serosa, and marked mesenteric edema. The mucosa of the abomasum of two of the animals was hemorrhagic with bloody content, and among the ruminal content of a bovine, leaves with morphological characteristics compatible with D. viscosa were observed. The livers of the three animals were enlarged, with accentuation of the lobular pattern. Histologically, centrilobular coagulation necrosis with congestion and hemorrhage was observed in the liver. Vacuolization and degeneration of hepatocytes were observed in the mid-zonal and periportal regions. The diagnosis of poisoning by D. viscosa leaves was based on epidemiological data, necropsy findings, and histopathological alterations. The presence of the plant in the rumen and in the grazing site of the affected cattle was essential for the diagnosis.(AU)

Neste trabalho, é descrito um surto de intoxicação espontânea por Dodonaea viscosa (D. viscosa) ocorrido em um rebanho de bovinos leiteiros, no município de Capão do Leão, no Rio Grande do Sul. Ocorreram três mortes em um lote de 16 bovinos da raça Jersey com idades entre três e quatro anos, mantidos em campo nativo. Os sinais clínicos observados foram apatia, queda na produção e anorexia, com morte em aproximadamente 48 horas após o início dos sinais. Os três bovinos foram necropsiados, e amostras de tecidos foram encaminhadas para exame histopatológico. Os achados de necropsia incluíam líquido serossanguinolento na cavidade abdominal, intestinos com serosas congestas e marcado edema de mesentério. A mucosa do abomaso de dois animais apresentava-se hemorrágica com conteúdo sanguinolento e, em meio ao conteúdo ruminal de um bovino foram observadas folhas com caracteres morfológicos compatíveis com D. viscosa. O fígado dos três animais estava aumentado, com acentuação do padrão lobular. Histologicamente no fígado havia necrose de coagulação centrolobular com congestão e hemorragia. Nas regiões médio-zonal e periportal observou-se vacuolização e degeneração dos hepatócitos. O diagnóstico de intoxicação pelas folhas D. viscosa foi baseado nos dados epidemiológicos, nos achados de necropsia e nas alterações histopatológicas. A presença da planta no rúmen e no local de pastoreio dos bovinos afetados foi fundamental para o diagnóstico.(AU)

Clinical safety of zafirlukast treatment during acute inflammatory reaction in nile tilapia (Oreochromis niloticus) / Segurança clínica do tratamento com zafirlucaste durante a reação inflamatória aguda em tilápia do nilo (Oreochromis niloticus)

Little is known about the toxicity of immune modulators in fish. Zafirlukast is an anti-inflammatory that antagonizes cysteine leukotriene receptors (CysLTR1). Aiming to study immunomodulatory treatments on fish health, this study evaluated the clinical safety of oral zafirlukast treatment, through biochemical and hematological analyzes during acute inflammatory reaction in Nile tilapia (Oreochromis niloticus), induced by Aeromonas hydrophila bacterins. 72 young tilapias were randomly divided in 9 aquariums (100 L each, n=8) to compose the following treatments: T0 (control), T1 (Treatment with 250 µg zafirlukast) and T2 (Treatment with 500 µg zafirlukast). Eight animals were evaluated per treatment in three periods: six, 24 and 48 hours post-inoculation (HPI), blood collection was performed for hematological and serum biochemical evaluation. The study of hepatic and renal functionality revealed that treatment with both doses of zafirlukast did not result in changes in the circulating values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, creatinine, triglycerides, cholesterol, and total protein, suggesting that the drug has not presented hepatotoxicity, as well as compromised liver and kidney functions. Tilapia submitted to treatment with 500 µg showed adverse hematological effects characterized by polycythemia associated with microcytosis. Therefore, oral treatment with zafirlukast has demonstrated clinical safety at a therapeutic dose of 250 µg in tilapia during acute aerocystitis, although hematological changes were observed in tilapia treated with overdose of this leukotriene blocker(AU)

Pouco se sabe sobre a toxicidade de imunomoduladores em peixes. Zafirlukast é um anti-inflamatório que antagoniza os receptores de leucotrienos cisteínicos (CysLTR1). Com o objetivo de estudar o efeito de tratamentos imunomoduladores sobre a saúde dos peixes, este estudo avaliou a segurança clínica do tratamento com zafirlucaste oral, por meio de análises bioquímicas e hematológicas durante reação inflamatória aguda em tilápia do Nilo (Oreochromis niloticus), induzida por bacterinas de Aeromonas hydrophila. Para tal, 72 tilápias jovens foram divididas aleatoriamente em 9 aquários (100 L cada, n=8) para compor os seguintes tratamentos: T0 (controle), T1 (Tratamento com 250 µg de zafirlucaste) e T2 (Tratamento com 500 µg de zafirlucaste). Oito animais foram avaliados por tratamento em três períodos: seis, 24 e 48 horas pós-inoculação (HPI), foi realizada coleta de sangue para avaliação hematológica e bioquímica sérica. O estudo da funcionalidade hepática e renal revelou que o tratamento com ambas as doses de zafirlucaste não resultou em alterações nos valores circulantes de aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina, creatinina, triglicerídeos, colesterol e proteína total, sugerindo que a droga não comprometeu as funções hepáticas e renais. As tilápias tratadas com 500 µg apresentaram efeitos hematológicos adversos caracterizados por policitemia associada a microcitose. Portanto, o tratamento oral com zafirlucaste demonstrou segurança clínica na dose de 250 µg em tilápias durante aerocistite aguda, embora alterações hematológicas tenham sido observadas em tilápias tratadas com sobredosagem deste bloqueador de leucotrieno.(AU)

Neurobehavioral and hepatic complications induced by acute inhalation exposure to abamectin in female rats of the Wistar strain treated with ginger (Zingiber officinale)

The study we conducted aimed to evaluate the acute toxicity of abamectin (ABM) (pesticide) on liver function and neurobehavioral by using the open field test. As a therapy, we have opted for a treatment based on natural antioxidants ginger extract (Zingiber officinale) mixed with olive oil to see the restorative effects during the experiment. The study was conducted on female Wistar rats. The latter was given an inhalation exposure of abamectin (ABM) at a dose CL50 > 5.04mg/L/1hr each morning for one week. The effects of this exposure showed a drop in body weight gain (g), a significant decrease in the relative and absolute weights liver (gm/100 gm body weight) accompanied by hepatic impairment indicating a significant disturbance of transaminases (AST/ALT), alkaline phosphatase (ALP) activity and significant behavioral changes. Administration of ginger (Zingiber officinale) extract at a dose of 3 ml mixed with olive oil at a dose of 1 ml/kg for 7 days orally (gavages) after inhalation indicates that ginger has a more remarkable and rapid effect on physical and mental health, it acts as a major means of defense and hepato-protective against toxicity.(AU)

Neurobehavioral and hepatic complications induced by acute inhalation exposure to abamectin in female rats of the Wistar strain treated with ginger (Zingiber officinale)

The study we conducted aimed to evaluate the acute toxicity of abamectin (ABM) (pesticide) on liver function and neurobehavioral by using the open field test. As a therapy, we have opted for a treatment based on natural antioxidants ginger extract (Zingiber officinale) mixed with olive oil to see the restorative effects during the experiment. The study was conducted on female Wistar rats. The latter was given an inhalation exposure of abamectin (ABM) at a dose CL50 > 5.04mg/L/1hr each morning for one week. The effects of this exposure showed a drop in body weight gain (g), a significant decrease in the relative and absolute weights liver (gm/100 gm body weight) accompanied by hepatic impairment indicating a significant disturbance of transaminases (AST/ALT), alkaline phosphatase (ALP) activity and significant behavioral changes. Administration of ginger (Zingiber officinale) extract at a dose of 3 ml mixed with olive oil at a dose of 1 ml/kg for 7 days orally (gavages) after inhalation indicates that ginger has a more remarkable and rapid effect on physical and mental health, it acts as a major means of defense and hepato-protective against toxicity.(AU)

Neurobehavioral and hepatic complications induced by acute inhalation exposure to abamectin in female rats of the Wistar strain treated with ginger (Zingiber officinale)

The study we conducted aimed to evaluate the acute toxicity of abamectin (ABM) (pesticide) on liver function and neurobehavioral by using the open field test. As a therapy, we have opted for a treatment based on natural antioxidants ginger extract (Zingiber officinale) mixed with olive oil to see the restorative effects during the experiment. The study was conducted on female Wistar rats. The latter was given an inhalation exposure of abamectin (ABM) at a dose CL50 > 5.04mg/L/1hr each morning for one week. The effects of this exposure showed a drop in body weight gain (g), a significant decrease in the relative and absolute weights liver (gm/100 gm body weight) accompanied by hepatic impairment indicating a significant disturbance of transaminases (AST/ALT), alkaline phosphatase (ALP) activity and significant behavioral changes. Administration of ginger (Zingiber officinale) extract at a dose of 3 ml mixed with olive oil at a dose of 1 ml/kg for 7 days orally (gavages) after inhalation indicates that ginger has a more remarkable and rapid effect on physical and mental health, it acts as a major means of defense and hepato-protective against toxicity.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.(AU)

O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.(AU)

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Fractal dimension in liver histological findings of Wistar rats experimentally intoxicated with venom of Crotalus durissus terrificus

Background: Accidents caused by venom of Crotalus durissus snakes, popularly known in Brazil as rattlesnake, aresecond in relation to the occurrence and first place in deaths in humans and animals, mainly due to the great neurotoxic,myotoxic, coagulant, nephrotoxic and hepatotoxic potential of their venom. The effects observed are due to the action ofthe main poison fractions and among them we can mention crotoxin (representing 50% of the total poison), crotamine,gyroxine and conxulxin. The present study aimed to analyze the liver of experimentally poisoned Wistar rats with venomof Crotalus durissus terrificus by means of histological and fractal analysis. The hypothesis is that the venom of Crotalusdurissus terrificus is can induce hepatic damage at the dose recommended in this study, that its alterations can be quantifiedby the fractal dimension and that the antiofidic serum botropic crotalic be able to minimize the hepatic lesions inducedby the venom.Materials, Methods & Results: Ninety rats were distributed into different groups and treated with: control group (GC, n= 30) 0.9% sodium chloride solution; venom group (GV, n = 30) crotalic venom at the dose of 1 mg/kg; (GVS, n = 30)crotalic venom at the dose of 1 mg/Kg and antiofidic serum 6 h after the application of the venom at the dose recommendedby the manufacturer. Liver samples were collected at 2 h (M1), 8 h (M2) and 24 h (M3) after venom administration andsubmitted to histological analysis and fractal dimension (DF) using the ImageJ® software and box-counting method. Procedures for collecting, processing and analyzing samples were standardized. For statistical analyzes, after the normalitywas verified by the Shapiro-Wilk test and homogeneity by the Bartlett test, the data were submitted to analysis of variance(ANOVA) with Duncan test contrast with a significance level of 5%. No significant lesions were observed in GC, howevernecrosis...(AU)