RESUMO
Global water scarcity entailed the use of treated wastewater (TWW) in agriculture, however, this water can vehiculate numerous pollutants into soil and further crops such as microplastics (MPs). To date, few studies had quantified the accumulation of MPs in soils and earthworms after irrigation with TWW as well as their toxicological effects. Hence, the main objective of the present work is to evaluate the toxicity of MPs using Lumbricus sp. earthworms collected from TWW irrigated soils with an increasing gradient of time (5 years, 16 years and 24 years). MPs determination in soil, as well as in earthworms were performed. The intestinal mucus was quantified, and cytotoxicity (Lysosomal membrane stability (LMS), Catalase (CAT) and glutathione-S-Transferase (GST) activities), neurotoxicity (Acetylcholinesterase activity (AChE)) and genotoxicity (Micronuclei frequency (MNi)) biomarker were assessed. Our results revealed that the use of TWW rendered MPs accumulation in earthworms' tissues and induce alteration on the intestinal mucus. An important cytotoxicity time-depending was observed being associated with an increase on genotoxicity. Overall, the present investigation highlights the ecotoxicological risk associated with the use of TWWs as an important driver of MPs and consequently measures are necessary to reduce MPs in wastewater treatment plans to improve this non-conventional water quality.
RESUMO
Heavy metal pollution is an important environmental issue causing several hazards to organisms. In the present study, we investigated the uptake and accumulation of heavy metals (Pb, Cd, Cu, and Zn) in chicken lungs after six months of breeding on polymetallic-contaminated area in Jebel Ressas village. Genotoxicity in term of micronuclei frequency as well as oxidative stress in term of enzymatic activities of Catalase (CAT), Glutathion-S-Transferase (GST) and malondialdehydes accumulation (MDA) were performed. In addition, gene expression levels involved in oxidative stress genes (cat, sod and gst), metal homeostasis (mt1 and mt4) and DNA metabolism (p53, bcl2, caspase 3 and DNA ligase) were detected. Exposed chicken lungs revealed an important heavy metal accumulation of Cd and Zn co-occurring with oxidative status modulation. Transcriptomic results unveiled an upregulation of oxidative stress and homeostasis genes. On the other hand, genes involved in DNA metabolism indicated cellular functioning towards cells death and apoptosis modulation. Moreover, the histopathological examination revealed lung lesions in the chickens exposed to heavy metal contamination. Our study highlights the hazardous effects of heavy metal pollution on chicken respiratory system.
Assuntos
Cádmio , Metais Pesados , Animais , Cádmio/toxicidade , Galinhas/metabolismo , Metais Pesados/análise , Estresse Oxidativo , Pulmão/metabolismo , DNA/metabolismoRESUMO
Proliferation of both stromal and epithelial components is a characteristic of fibroepithelial cancers of the breast. Certain fibroepithelial tumors of the breast, such as fibradenomas and phyllodes tumors, are challenging to distinguish and categorize. To find biomarkers for early diagnosis and improved disease management, it is crucial to deepen our understanding of the molecular pathogenesis pathways and tumor biology of PTs. It has been demonstrated that microRNAs (miRNAs) have significant roles in cancers; the expression pattern of miRNAs can help with cancer categorization and treatment. In contrast, little is understood about miRNAs in breast fibroepithelial cancers. This study was conducted retrospectively with the goal of assessing the expression of six mature miRNAs (hsa-miR-21, hsa-miR-155, hsa-miR-182, hsa-miR-34a, hsa-miR-148a, and hsa-miR-205) in breast fibroepithelial cancers using real-time PCR and predicting these miRNAs' targets using computational techniques. This study comprised 64 patients in total-55 with phyllodes tumors and 9 with fibroadenoma. The research was carried out at the Farhat Hached University Hospital's pathology department in Tunisia. These particular miRNAs expression levels were evaluated via qRT-PCR, and in silico techniques were utilized to predict potential miRNA targets. Analysis of miRNA expression in fibroadenoma and phyllodes tumor tissues revealed that miR-21, miR-155 and miR-182 were upregulated in PTs compared to fibroadenoma and normal tissues. We reported that miR-34a, miR-148a and miR-205 were downregulated in both borderline and malignant PTs compared to fibroadenoma and normal tissue. In silico miRNA target prediction suggested the involvement of these molecules in a wide context of cell signaling pathways.
RESUMO
BACKGROUND: Synovial sarcoma is an uncommon soft tissue malignancy that mainly occurs near tendon sheath and bone joints. Primary intra-abdominal location is exceedingly rare and characterized by non-specific clinical signs. CASE PRESENTATION: We report the case of a young female without medical history who presented with acute abdominopelvic pain. Ultrasound echography revealed a right mass measuring 7 cm in greater diameter cystic with solid areas, likely of ovarian origin. A coelioscopy with peritoneal biopsies was performed. Histological examination with immunohistochemistry concluded the diagnosis of GIST. The patient was referred to the surgery department and after laboratory routine analysis and computed tomography, the patient was proposed to surgical management. Per-operative findings revealed a mesenteric mass locally invading the greater omentum and the appendicular wall. Pathological examination with immunochemistry confirmed the diagnosis of mesenteric monophasic synovial sarcoma invading the appendicular wall with positive surgical margins. Chemotherapy was proposed with a good response. Our patient is free from disease 9 months later. CONCLUSIONS: We aimed through this case report to discuss mesenteric presentation monophasic SS, mimicking ovarian malignancy, emphasizing clinicopathological features and differential diagnoses.
RESUMO
Vitis vinifera leaves (VVL) are agro-industrial waste. In the current study, the phytochemical profile of V. vinifera leaves extracts (VVLE) of two Tunisian autochthonous accessions was determined via LC-UV-ESI/MS, and their antioxidant and hepatoprotective properties were also assessed. Mice were pretreated orally with VVLE (7.5, 15 and 30 mg/kg) for 7 days, and then received acutely and by i.p. a solution CCl4 at 12% in sunflower oil (v/v). Serum levels of hepatic markers, oxidative stress indicators in liver tissue and histological changes were assessed. LC-UV-ESI/MS analysis revealed four phenolic compounds identified in both extracts with quercetin-3-O-glucuronide being the dominant constituent (23.32 ± 1.06 vs. 10.24 ± 0.12 mg/g DM, p < 0.05 for wild and cultivated accessions, respectively). The Antioxidant activity revealed a significant difference between the genotypes. Moreover, the VVLE of the wild "Nefza-I" ecotype was the most active based on antioxidant assays. Furthermore, the results showed that pre-treatment, especially with VVLE, of the wild ecotype "Nefza-I", attenuated CCl4-induced acute liver injury in a dose-dependent manner, as demonstrated by the decrease in the activities of hepatic serum function markers. This was also evidenced by a decrease in the levels of lipoperoxidation and histological damage in the liver, as well as a restoration of antioxidant enzyme activities (SOD and catalase) and an increase in the hepatic glutathione content. Our results demonstrate that VVLE possesses protective effects on CCl4-induced liver injury. Overall, the wild ecotype "Nefza-I" extract could serve as an effective protector against CCl4-induced hepatocellular oxidative stress.
RESUMO
Hepatic adenomatosis is a rare disease consisting of multiple adenomas in otherwise-normal liver parenchyma. Though the discovery of this entity goes back several years, its diagnosis is still challenging in terms of its definition and pathophysiology. Clinically, patients may be completely asymptomatic and the diagnosis is only made incidentally through imaging tests. The discovery could be made when complications occur such as intraperitoneal hemorrhage with hypovolemic shock due to the rupture of an adenoma. We report a fatal case of a ruptured adenoma in a case of hepatic adenomatosis discovered at autopsy. In order to achieve a better view of this disease, we conducted a literature review on this subject describing the pathogenesis, manifestations, and autopsy contribution to addressing this entity.
Assuntos
Adenoma , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Autopsia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/patologia , Ruptura , Tomografia Computadorizada por Raios XRESUMO
The sarcoid-like reaction is a rare autoinflammatory disease that can affect lymph nodes or organs but does not meet the diagnostic criteria for systemic sarcoidosis. Several drug classes have been associated with the development of a systemic sarcoid-like reaction, which defines drug-induced sarcoidosis-like reactions and can affect a single organ. Anti-CD20 antibodies (rituximab) have rarely been reported as responsible for this reaction and this adverse effect has mainly been described during the treatment of Hodgkin's lymphoma. We report a unique case of a sarcoid-like reaction complicating rituximab following the treatment of a mantle cell lymphoma and interesting only the kidney. The 60-year-old patient presented with severe acute renal failure 6 months after the end of his r-CHOP protocol and the urgent renal biopsy revealed acute interstitial nephritis rich in granulomas without caseous necrosis. After ruling out other causes of granulomatous nephritis, a sarcoid-like reaction was retained since infiltration was limited to the kidney. The temporal relationship between rituximab administration and the sarcoid-like reaction onset in our patient supported the diagnosis of a rituximab-induced sarcoidosis-like reaction. Oral corticosteroid treatment led to rapid and lasting improvement in renal function. Clinicians should be warned of this adverse effect and regular and prolonged monitoring of renal function should be recommended during the follow-up of patients after the end of treatment with rituximab.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Linfoma , Nefrite Intersticial , Sarcoidose , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Rim/fisiologia , Sarcoidose/induzido quimicamente , Sarcoidose/tratamento farmacológicoRESUMO
Due to anthropogenic activities, various pollutants can be found in agricultural soil, such as cadmium (Cd) and 2,4-dichlorophenoxyacetic acid (2,4-D). They are highly toxic and can have a negative impact on soil fertility. For remediation strategies, biochar has acquired considerable attention due to its benefits for agriculture. However, we should recognize the ecological risk posed by biochar use. In addition, little is known about its non-desirable effects on soil organisms such as earthworms, especially in the case of soil remediation. In this study, earthworms (Eisenia andrei) were exposed to soil contaminated with Cd (0.7 mg/kg), (2,4-D) (7 mg/kg), and a mixture of the two in the presence and absence of biochar (2%). A 7- and 14-day incubation experiment was carried out for this purpose. Cd and 2,4-D uptakes in earthworms' tissues, oxidative stress, cytotoxic response, DNA damage, histopathological changes, and gene expression level were assessed. Results suggested that biochar increased the bioavailability of Cd and 2,4-D and the frequency of micronuclei (MNi) and decreased the lysosomal membrane stability (LMS) in earthworms. Also, histopathological examination detected numerous alterations in animals exposed to the contaminants without any amelioration when biochar was added. The biochemical response of earthworms in terms of oxidative stress demonstrates that in the presence of biochar, animals tend to alleviate the toxicity of Cd and 2,4-D. This was also supported by transcriptomic analyses where expression gene levels related to oxidative stress were upregulated in earthworms exposed to Cd and 2,4-D + biochar. The present investigation brought new insights concerning the use of biochar in agriculture.
Assuntos
Herbicidas , Oligoquetos , Poluentes do Solo , Animais , Cádmio/análise , Poluentes do Solo/análise , Herbicidas/análise , Carvão Vegetal/farmacologia , Fenoxiacetatos/metabolismo , Fenoxiacetatos/farmacologia , Solo/química , Ácido 2,4-Diclorofenoxiacético/toxicidade , Ácido 2,4-Diclorofenoxiacético/metabolismoRESUMO
AIMS: Interferon-beta (IFNß), the most widely prescribed medication for multiple sclerosis, is generally considered safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as thrombotic microangiopathy. A few mechanisms have been proposed to explain how interferon causes thrombotic microangiopathy, but immunological studies have been unable to pin this phenomenon down to a single pathophysiologic pathway. The aim of this article was to report a new mechanism explaining Interferon beta related thrombotic microangiopathy. METHODS: We report thrombotic microangiopathy in a 28-year-old male receiving interferon-beta treatment for multiple sclerosis. RESULTS: After three years of starting interferon beta therapy, the patient presented with malignant hypertension causing seizures, rapidly progressive renal failure requiring haemodialysis and haemolytic anaemia. Corticosteroid and plasma exchange sessions permitted haemolysis control. Nonetheless, the patient remained hemodialysis-dependent. Exploration of the complement system found a complement factor I deficiency whose activity normalized at the control carried out after 2 years. CONCLUSION: IFNß treatment may cause complement factor I deficit, which can lead to thrombotic microangiopathy and severe renal failure.
Assuntos
Esclerose Múltipla , Insuficiência Renal , Microangiopatias Trombóticas , Masculino , Humanos , Adulto , Interferon beta/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Microangiopatias Trombóticas/induzido quimicamente , Insuficiência Renal/complicaçõesRESUMO
Acute interstitial nephritis (AIN) is a relevant cause of acute renal failure. Drugs are the predominant cause, followed by infections and idiopathic lesions. AIN, as a form of hypersensitivity reaction, is an uncommon manifestation in the setting of human parasitic infections. We report a case of a polyparasitic infection (Giardia lamblia, Entamoeba coli, and Endolimax nana) resulting in a severe biopsy-proven AIN in a 61-year-old male patient. Despite the antiparasitic treatment followed by corticosteroid therapy, and during the 6-month follow-up period, the patient remained dialysis-dependent, and he developed autoimmune hemolytic anemia. Extensive search for another infection or neoplasia was negative. Immunological tests were also negative. The resulting hypersensitivity reaction to the triple parasite infection would have led to fatal evolution for the kidneys affected by this unusual type of AIN.
Assuntos
Anemia Hemolítica , Dermatite , Nefrite Intersticial , Masculino , Humanos , Pessoa de Meia-Idade , Nefrite Intersticial/diagnósticoRESUMO
Background: Congenital diaphragmatic hernia (CDH) is a congenital malformation of the diaphragm, resulting in the herniation of the abdominal organs into the thoracic cavity. If not properly diagnosed before or at birth, CDH represents a life-threatening pathology in infants and a major cause of death. We present a fatal case of congenital diaphragmatic hernia corresponding to Bochdalek hernia, discovered incidentally during a sudden death's autopsy of an infant. To achieve a better view of the range of these anomalies, we also conducted a literature review on this subject describing the pathogenesis, manifestations, diagnosis, and autopsy contribution to addressing these CDH. Case presentation: The case involved a 4-month-old female infant who presented sudden respiratory difficulties after breastfeeding. External examination found marked cyanosis with no evidence of trauma. Upon opening the chest cavity, the stomach, markedly distended, was occupying much of the left pleural cavity. The left lung was compressed and displaced superiorly, and the heart was also compressed and deviated to the right. This mediastinal deviation was due to an ascension of the stomach into the chest cavity through a 2 × 1.5 cm defect in the posterior left hemidiaphragm. Further examination remarked an ecchymotic appearance of the stomach portion entrapped in the hernia defect suggesting recent strangulation of the stomach. The lungs showed atelectasis with signs of pulmonary infection in the histology study. Conclusions: CDH might be considered uncommon and not always mentioned in the list of sudden death in infant causes. Forensic pathologists should know of this malformation in order to apply the best autopsy techniques and thus allow positive feedback to pediatricians considering the possible legal implications.
RESUMO
Triple-negative breast cancer (TNBC) is a very heterogeneous disease and refers to a subgroup of breast cancer. The purpose of this study was to describe the clinical, pathological and molecular features of TNBC. We conducted a retrospective analysis of 56 cases of TNBC diagnosed in the Department of Pathology at the Farhat Hached University Hospital over a period of three years (2018-2020). The incidence of TNBC was 5.62% and the mean age of the patients was 50.36 years. The most frequent reason for consultation was the discovery of breast nodules (98.21%). The diagnosis of TNBC was confirmed in 24 cases (42.86%) based on the analysis of mastectomy specimens. Invasive carcinoma of no special type (NST) was the most common histological type (47 cases; 82.5%). Mean tumor size was 35.5 mm. SBR grading was only specified in 42 cases (73.68%). Grade III was the most predominant type (78.6%, n = 33). The notion of lymph node metastasis was found in 44 reports and lymph node invasion was reported in 19 patients (43.2%). Immunohistochemical study showed that all patients were hormone receptor-negative (RO and RP) with no Her2 overexpression (n = 56; 100). This study results are generally in agreement with literature data. Despite recent molecular classifications, there is no clinically verified diagnostic test allowing for clear therapeutic standardization.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Receptores de Progesterona , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUNDS: Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain. The aim of this work was to explore the hepatotoxic and nephrotoxic effects of FEN on Wistar rats. METHODS: The study involved five groups: a control group and four groups treated with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 consecutive days. Histological examination and biochemical analysis of hepatic and renal biomarkers were performed. The malondialdehyde (MDA), protein carbonyl levels, and antioxidant enzymes activities were measured. Comet assay was conducted to explore FEN genotoxicity. RESULTS: FEN induced a disturbance of the hepatic and renal functions as evidenced by an increase in AST, ALT, ALP, creatinine, and uric acid levels and histopathological modifications in the two examined tissues. FEN increased hepatic and renal lipid peroxidation and protein oxidation. The activities of liver and kidney SOD, CAT, GPX, and GST are increased significantly in FEN-treated rats at doses of 2 and 4 mg/kg bw. However, with the dose of 8 mg/kg bw of FEN, these activities are decreased. Moreover, FEN increased DNA damage in a dose-dependent manner. CONCLUSION: FEN was hepatotoxic and nephrotoxic very likely through induction of oxidative stress.
Assuntos
Acaricidas , Doença Hepática Induzida por Substâncias e Drogas , Animais , Ratos , Antioxidantes/metabolismo , Ratos Wistar , Creatinina , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia , Acaricidas/metabolismo , Acaricidas/farmacologia , Estresse Oxidativo , Fígado/metabolismo , Rim , Malondialdeído/metabolismo , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Superóxido Dismutase/metabolismoRESUMO
Although the significance of DNA mismatch repair (MMR) protein expression in colorectal cancer is well-established, it remains contentious in extra-colorectal cancers and mainly in gastric adenocarcinoma. Data from Africa and Arab world remain limited. This study explored the MMR expression in gastric adenocarcinoma and evaluated its clinicopathological and prognostic signification among Tunisian patients. A retrospective study of 72 gastric adenocarcinomas was carried out. Clinicopathological particularities and patient outcomes were recorded. MMR expression was determined by immunohistochemistry on whole sections of archived material. Survival analysis was realized utilizing the Kaplan-Meier estimates and Log-Rank test. Expression of MMR proteins was observed in 84.7% of gastric adenocarcinoma samples. The 11 remaining samples (15.3%) exhibited an altered pattern of MMR protein. A significant association was identified between deficient MMR expression and advanced age (p = 0.03), intestinal type (p = 0.04) and lymph node metastases (p = 0.04). No other significant relationship was observed with the remaining selected tumor features. Patient survival was significantly associated with lymph node invasion (p = 0.002), distant metastases (p = 0.02) and tumor differentiation (p = 0.03), but not with MMR status (p = 0.83). MMR deficiency was related to advanced-age, intestinal type and nodal metastasis, but not to survival of Tunisian patients with gastric adenocarcinoma. Larger multicenter studies with additional molecular investigation are required to more explore these tumors.
Bien que l'importance de l'expression des protéines de réparation des mésappariements de l'ADN (MMR) dans le cancer colorectal soit bien établie, elle reste controversée dans les cancers extra-colorectaux et principalement dans l'adénocarcinome gastrique. Les données de l'Afrique et du monde arabe restent limitées. Cette étude a exploré l'expression des protéines MMR dans l'adénocarcinome gastrique et a évalué sa signification clinicopathologique et pronostique chez les patients tunisiens. Une étude rétrospective de 72 adénocarcinomes gastriques a été réalisée. Les particularités clinicopathologiques et pronostiques des patients ont été enregistrées. L'expression des protéines MMR a été déterminée par immunohistochimie. L'analyse de survie a été réalisée en utilisant la méthode de Kaplan-Meier et le test Log-Rank. L'expression des protéines MMR a été observée dans 84,7 % des échantillons d'adénocarcinome gastrique. Les 11 cas restants (15,3 %) présentaient un profil d'expression altérée des protéines MMR. Une association significative a été identifiée entre l'expression déficiente de MMR et l'âge avancé (p = 0,03), le type intestinal (p = 0,04) et les métastases ganglionnaires (p = 0,04). Aucune autre relation significative n'a été observée avec les autres caractéristiques tumorales sélectionnées. La survie des patients était significativement associée à l'envahissement des ganglions lymphatiques (Log Rank, p = 0,002), aux métastases à distance (Log Rank, p = 0,02) et à la différenciation tumorale (Log Rank, p = 0,03), mais pas à l'expression de MMR (Log Rank, p = 0,03). Rang, p = 0,83). Le déficit de l'expression des protéines MMR était lié à l'âge avancé, au type intestinal et aux métastases ganglionnaires, mais pas à la survie des patients tunisiens ayant un adénocarcinome gastrique. Des études multicentriques avec des investigations moléculaires supplémentaires sont nécessaires pour explorer davantage le cancer gastrique avec expression déficiente des protéines MMR.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , DNA , Reparo de Erro de Pareamento de DNA , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Bromuconazole is a widely used triazole against various fungi disease. It's employment provokes harmful effects on the environment and human health. In the present study, we explored bromuconazole toxic effects in both rat brain tissue and SH-SY5Y cell line. METHODS: Male Wistar rats were administrated orally with Bromuconazole (NOEL/4, NOEL o and NOEL ×2) daily for consecutive 28 days. In addition, neuronal SH-SY5Y cell line was used. The rat brains and SH-SY5Y cells were collected and analysed for AChE activity, oxidative stress biomarkers, genotoxicity and histopathological alterations. RESULTS: Our results showed that rat exposure to bromuconazole at doses corresponding to NOEL/4, NOEL and NOEL ×2 caused brain histopathological alteration and decrease in acetylcholine esterase (AChE) activity. In SH-SY5Y cell line, bromuconazole strongly induced cell mortality with an IC50 about 250 µM. Bromuconazole induced also DNA damage as assessed by comet assay in both rat brain tissue and SH-SY5Y cell. Moreover, bromuconazole increased ROS production, malondialdehyde (MDA) and protein carbonyl (PC) levels and enhanced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), Glutathione-S-transferase (GST) and peroxidase (GPx) in the two studied systems. CONCLUSION: Therefore, we can deduce that bromuconazole-caused neurotoxicity may be related to oxidative statue disturbance.HIGHLIGHTSBromuconzole causes oxidative stress in the brain tissue of male Wistar rats.Bromuconazole enhances MDA, PC levels and induces DNA damage in rat brain.Bromuconazole provokes disturbance of the neuronal antioxidant system.Bromuconazole induces histopathological alterations in rat brain.Bromuconazole exposure induced cytotoxic effects and DNA damage in SH-SY5Y cells.Bromuconazole exposure induced oxidative stress in SH-SY5Ycells.
Assuntos
Lesões Encefálicas , Neuroblastoma , Animais , Encéfalo/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Dano ao DNA , Furanos , Glutationa Transferase/genética , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Triazóis/toxicidadeRESUMO
Fenpyroximate (FEN) is an acaricide used in agriculture / horticulture to control spider mites and leafhoppers. It inhibits the transport of mitochondrial electrons at the level of NADH-coenzyme Q oxidoreductase (complex I). Despite the implication of inhibition of mitochondrial complex I in neurotoxicity, especially in neurodegenerative diseases, data concerning FEN neurotoxicity remain limited. Thus, the present study was designed to investigate the toxic effect of FEN on rat brain tissue and on human neuroblastoma cells (SH-SY5Y). Rat exposure to FEN at three different doses (4.8, 9.6 and 48 mg / Kg bw) for 28 consecutive days resulted in histopathological modifications in brain tissue and a significant decrease in acetylcholinesterase activity. Further, FEN significantly enhanced lipid peroxidation and protein oxidation in rat brain and disturbed activities of antioxidant enzymes (SOD, CAT, GPx, and GST). Besides, FEN was found to induce DNA damage in a significant and dose-dependent manner in rat brain as assessed by the comet assay. To better understand FEN neurotoxic effect, we monitored our study on SH-SY5Y cells. We confirm our data found in rat brain tissue. In fact, FEN induced cell mortality in a concentration dependent manner. It over-produced intracellular ROS and lipid peroxidation and enhanced SOD and CAT activities. FEN was also found to induce DNA damage in SH-SY5Y cells. Moreover, FEN induced a loss of mitochondrial membrane potential, which confirms FEN mitochondrial impairing activity. Acridine Orange-Bromure Etidium (AO-BE) cell staining indicated that FEN enhanced the percentage of apoptotic cells in a concentration dependent manner. Further, pretreatment with a general caspases inhibitor (ZVAD-FMK), reduced significantly the FEN induced cell mortality. We also shown that FEN increased caspase 3 activity. These findings suggested, for the first time, the possibility of the involvement of mitochondrial pathway in FEN-induced cell apoptosis.
Assuntos
Neuroblastoma , Acetilcolinesterase/genética , Animais , Apoptose , Benzoatos , Encéfalo , Linhagem Celular Tumoral , Sobrevivência Celular , Dano ao DNA , Humanos , Estresse Oxidativo , Pirazóis , Ratos , Ratos Wistar , Superóxido Dismutase/genéticaRESUMO
INTRODUCTION: Breast cancer is a major public health problem worldwide. It is the leading cause of cancer deaths in females. In developing countries like Tunisia, the frequency of this cancer is still growing. The aim of this study was to determine the crude and standardized incidence rates, trends and predictions until 2030 of breast cancer incidence rates in a Tunisian governorate. METHODS: This is a descriptive study including all female patients diagnosed with breast cancer in Monastir between 2002 and 2013. The data were collected from the cancer register of the center. Tumors were coded according to the 10th version of international classification of disease (ICD-10). Trends and predictions until 2030 were calculated using Poisson linear regression. RESULTS: A total of 1028 cases of female breast cancer were recorded. The median age of patients was 49 years (IQR: 41-59 years) with a minimum of 16 years and a maximum of 93 years. The age-standardized incidence rate (ASR) was of 39.12 per 100000 inhabitants. It increased significantly between 2002 and 2013 with APC of 8.4% (95% CI: 4.9; 11.9). Prediction until 2030 showed that ASR would reach 108.77 (95% CI: 57.13-209.10) per 100000 inhabitants. CONCLUSION: The incidence and the chronological trends of breast cancer highlighted that this disease is of a serious concern in Tunisia. Strengthening preventive measures is a primary step to restrain its burden.
Assuntos
Neoplasias da Mama , Adulto , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Incidência , Classificação Internacional de Doenças , Pessoa de Meia-Idade , Sistema de Registros , Tunísia/epidemiologiaRESUMO
Coastal areas are worldwide subject to large inputs of anthropogenic wastes that are discharged directly into inshore waters, where they will be weathered into small microplastics (MPs) of up to a size <20 µm. This study provides information about the presence of small environmental MPs (≤3 µm) in the liver of adult benthopelagic fish Serranus scriba (Linnaeus 1758), caught from three coastal regions in Tunisia distinguished by different patterns of human activity. Polymer composition in fish liver was identified using Raman microspectroscopy. Results revealed differences in the abundance, size distribution and presence of plastic additives over the investigated sites. Polyethylene-vinyl acetate (PEVA: 34% particles/g of tissue), high density polyethylene (HDPE: 24.4%) and the two smaller size classes, i.e. 3-1.2 µm and 1.2-0.45 µm, were the most abundant MPs types and size distribution found, respectively, in Bizerte channel (BC) site (Bizerte city, Tunisia). Moreover, at hepatic level data showed a significant site-dependent cytotoxicity expressed by changes in malondialdehyde (MDA) content, presence of reactive oxygen species (ROS) expressed by altered level of catalase (CAT) and glutathione-S-transferase (GST) activities and in the content of metallothioneins (MTs), as well as genotoxicity by changes in the amount of micronucleus (MN), and neurotoxicity by altered activity of acetylcholinesterase (AChE). A innovative metabolomics analysis was also performed to further investigate the distinct patterns of key metabolite changes in the liver of Serranus scriba. A total of 36 metabolites were significantly affected, mainly involved in energy, amino acid and osmolyte metabolism. These findings emphasised for the first time a close relationship between the source, abundance and size ranges of environmental MPs ≤ 3 µm and their hepatotoxicity in wild organisms.
Assuntos
Bass , Doença Hepática Induzida por Substâncias e Drogas , Poluentes Químicos da Água , Acetilcolinesterase/metabolismo , Animais , Bass/metabolismo , Monitoramento Ambiental , Metabolômica , Microplásticos , Plásticos/toxicidade , Polietileno/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Background: Malaria is the first parasitic infection endemic in the world caused by parasites species of Plasmodium. Cerebral malaria (CM) is a rapidly progressive and severe form of Plasmodium falciparum infection, characterized by a greater accumulation of red blood cells parasitized by Plasmodium falciparum in the brain. The diagnosis of malaria is usually made in living patients from a blood sample taken in the course of a fever on return from an endemic country, whereas CM, often associated with fatal outcomes even in treated subjects, is usually diagnosed at autopsy. Case presentation: We present the case of a 36-year-old man who died a few days after returning from a business trip to the Ivory Coast. As a result of an unclear cause of death, a medicolegal autopsy was ordered. Autopsy findings revealed massive congestion and edema of the brain with no other macroscopic abnormalities at organ gross examination. Histology and laboratory tests were conducted revealing a Plasmodium falciparum infection, with numerous parasitized erythrocytes containing dots of hemozoin pigment (malaria pigment) in all examined brain sections and all other organs. Death was attributed to cerebral malaria with multiple organ failure. Conclusions: This report summarizes several features for the diagnosis of malaria and how postmortem investigations, as well as histology and laboratory diagnosis, may lead to a retrospective diagnosis of a fatal complicated form with cerebral involvement.