Otoprotection Mechanisms Against Oxidative Stress Caused by Cisplatin

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.

Efecto de la n-acetilcisteina inhalada en el desarrollo de fibrosis pulmonar de ratas intoxicadas con paraquat / Effect of n-acetylcisteine inhaled in the development of pulmonary fibrosis of intoxicated rats with paraquat

El Paraquat (PQ) es un herbicida de contacto bipiridilico ampliamente utilizado en agricultura. La intoxicación en humanos por este agente ocasiona fibrosis pulmonar. Evaluamos los cambios histológicos pulmonares de ratas intoxicadas con PQ y tratadas con N-aceticisteina (NAC) administrada vía inhalatoria. Realizamos un estudio experimental descriptivo con 25 ratas adultas, machos cepa Wistar, divididas en cinco grupos. Al grupo I no se les administro ni PQ ni NAC. Grupo II, recibió NAC inhalada a 15mg/kg diaria c/12 horas. Grupo III, PQ vía oral (VO) 15mg/kg. Grupo IV, PQ a 15mg/kg, por VO y a la hora NAC 150mg/kg. Grupo V, PQ a 15mg/kg, por VO y a las seis horas NAC dosis de 150mg/kg. Los pulmones fueron extraídos y se evaluaron mediante cortes histológicos. Resultados: Los grupos I y II (supervivencia del 100%, n=10) no desarrollaron sintomatología de intoxicación. Grupos III, IV y V predominaron síntomas respiratorios, diversos grados de edema pulmonar, enfisema, congestión vascular y hemorragia intra-alveolar focal. La eficacia de la NAC sobre la intoxicación por PQ en términos de sobrevivencia al primer día, fue del 100% y al segundo día, fue del 80% (p= 0,005; prueba Chi-cuadrado). El PQ indujo un proceso inflamatorio (agudo-crónico) por infiltrado de segmentados neutrófilos y linfocitos, lo cual fue revertido parcialmente por la administración inhalada de NAC. Conclusión: Los cambios histopatológicos observados a nivel pulmonar fueron aminorados por el tratamiento con NAC, lo que sugiere un posible efecto protector de este fármaco sobre el daño oxidativo inducido por el herbicida

Paraquat (PQ) is a bipyridyl contact herbicide widely used in agriculture. Intoxication in humans by this agent causes pulmonary fibrosis. We evaluated pulmonary histological changes of rats intoxicated with PQ and treated with N-acetycysteine (NAC) administered via inhalation. We conducted a descriptive experimental study with 25 adult rats, male Wistar strain, divided into five groups. Group I was not administered PQ or NAC. Group II, received NAC inhaled at 15mg/kg daily c/12 hours. Group III, PQ orally (VO) 15mg/ kg. Group IV, PQ at 15mg/kg, by VO and at hour NAC 150mg/ kg. Group V, PQ at 15mg/kg, by VO and at six hours NAC dose of 150mg/kg. The lungs were extracted and evaluated by histological sections. Results: Groups I and II (100% survival, n=10) did not develop intoxication symptoms. Groups III, IV and V predominantly respiratory symptoms, various degrees of pulmonary edema, emphysema, vascular congestion and focal intra-alveolar hemorrhage. The efficacy of NAC on PQ poisoning in terms of survival on the first day was 100% and on the second day it was 80% (p = 0.005, Chi-square test). The PQ induced an inflammatory process (acute-chronic) by infiltration of segmented neutrophils and lymphocytes, which was partially reversed by the inhaled administration of NAC. Conclusion: The histopathological changes observed at the pulmonary level were reduced by the treatment with NAC, which suggests a possible protective effect of this drug on the oxidative damage induced by the herbicide.

Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury / Efeitos da N-acetilcisteína e pentoxifilina na lesão pulmonar remota em um modelo de lesão de isquemia/reperfusão de membro posterior em ratos

Objective : To investigate the effects of N-acetylcysteine (NAC) and pentoxifylline in a model of remote organ injury after hind-limb ischemia/reperfusion (I/R) in rats, the lungs being the remote organ system. Methods : Thirty-five male Wistar rats were assigned to one of five conditions (n = 7/group), as follows: sham operation (control group); hind-limb ischemia, induced by clamping the left femoral artery, for 2 h, followed by 24 h of reperfusion (I/R group); and hind-limb ischemia, as above, followed by intraperitoneal injection (prior to reperfusion) of 150 mg/kg of NAC (I/R+NAC group), 40 mg/kg of pentoxifylline (I/R+PTX group), or both (I/R+NAC+PTX group). At the end of the trial, lung tissues were removed for histological analysis and assessment of oxidative stress. Results : In comparison with the rats in the other groups, those in the I/R group showed lower superoxide dismutase activity and glutathione levels, together with higher malondialdehyde levels and lung injury scores (p < 0.05 for all). Interstitial inflammatory cell infiltration of the lungs was also markedly greater in the I/R group than in the other groups. In addition, I/R group rats showed various signs of interstitial edema and hemorrhage. In the I/R+NAC, I/R+PTX, and I/R+NAC+PTX groups, superoxide dismutase activity, glutathione levels, malondialdehyde levels, and lung injury scores were preserved (p < 0.05 for all). The differences between the administration of NAC or pentoxifylline alone and the administration of the two together were not significant for any of those parameters (p > 0.05 for all). Conclusions : Our results suggest that NAC and pentoxifylline both protect lung tissue from the effects of skeletal muscle I/R. However, their combined use does not appear to increase the level of that protection.

Objetivo : Investigar os efeitos da N-acetilcisteína (NAC) e pentoxifilina em um modelo de lesão pulmonar remota após isquemia/reperfusão (I/R) de membro posterior em ratos. Métodos : Trinta e cinco ratos Wistar machos foram divididos em cinco grupos (n = 7/grupo), cada qual submetido ao seguinte: operação simulada (grupo controle); isquemia de membro posterior, induzida por pinçamento da artéria femoral esquerda por 2 h, seguida por de 24 h de reperfusão (grupo I/R); e isquemia de membro posterior, como descrito acima, seguida de injeção intraperitoneal (antes da reperfusão) de 150 mg/kg de NAC (grupo I/R+NAC), 40 mg/kg de pentoxifilina (grupo I/R+PTX) ou ambas (grupo I/R+NAC+PTX). Ao final do experimento, tecidos pulmonares foram removidos para análise histológica e avaliação do estresse oxidativo. Resultados : Comparados aos ratos dos outros grupos, os do grupo I/R apresentaram menor atividade de superóxido dismutase e menores níveis de glutationa, além de maiores níveis de malondialdeído e maiores escores de lesão pulmonar (p < 0,05 para todos). Infiltração celular inflamatória intersticial dos pulmões também foi bem maior no grupo I/R do que nos outros grupos. Além disso, os ratos do grupo I/R apresentaram vários sinais de edema intersticial e hemorragia. Nos grupos I/R+NAC, I/R+PTX e I/R+NAC+PTX, a atividade de superóxido dismutase, níveis de glutationa, níveis de malondialdeído e escores de lesão pulmonar foram preservados (p < 0,05 para todos). As diferenças entre a administração de NAC ou pentoxifilina isoladamente e a das duas combinadas não foi significativa para nenhum desses parâmetros (p > 0,05 para todos). Conclusões : Nossos resultados sugerem que tanto NAC quanto pentoxifilina protegem o tecido pulmonar dos efeitos de I/R de músculo esquelético. Entretanto, seu uso combinado não parece aumentar o nível dessa proteção.

Uso de N-acetilcisteína tópica en ictiosis: experiencia clínica en una serie de casos / Use of topical N-acetylcysteine ​​in ichthyosis: clinic experience in a series of cases

Las ictiosis son trastornos generalizados de la queratinización, que se caracterizan por presentar hiperqueratosis y/o descamación. El tratamiento es sintomático e incluye terapias tópicas y sistémicas. La N-Acetilcisteína (NAC) tópica ha mostrado utilidad en algunos reportes. Se describirá la experiencia con el uso de NAC 10% y urea 5% en novobase II (NB II) en 6 pacientes con distintos tipos de ictiosis hereditarias. Caso Nº1: Escolar masculino de 7 años con Ictiosis lamelar (IL) en tratamiento con fórmula de NAC hace 4 años con buena respuesta. Caso N°2, 3 y 4: Escolar masculino de 7 años, escolar masculino de 5 años y lactante masculino de 1 año 8 meses con Ictiosis recesiva ligada a X (IRLX), en tratamiento con fórmula de NAC con buena respuesta. Caso N°5: Mujer de 18 años con Eritrodermia ictiosiforme congénita (EIC), inicia tratamiento con fórmula de NAC, pero se suspende por mala tolerancia. Caso N°6: Preescolar femenina de 3 años, con Ictiosis epidermolítica (IE), inicia tratamiento con fórmula de NAC con mala tolerancia por lo que también se suspende. Se evaluaron los efectos de la fórmula de NAC en diferentes tipos de ictiosis, mostrando un buen perfil de seguridad y eficacia en IL e IRLX, sin embargo, en EIC e IE su uso estuvo restringido por efectos adversos. El tratamiento con fórmula de NAC presenta buena respuesta y tolerancia en pacientes con IL e IRLX, por lo que podría considerarse en el tratamiento habitual de estos pacientes.

Ichthyosis are generalized disorders of keratinization, characterized by hyperkeratosis and/or scaling. Treatment is symptomatic and includes topical and systemic therapies. Topical N-acetylcysteine (NAC) has shown utility in some reports. We describe the experience using 10% NAC and 5% urea in novobase II (NB II) in 6 patients with different types of hereditary ichthyosis. Case N°1: 7-year-old boy with lamellar Ichthyosis (IL) in treatment with NAC formula 4 years ago, with good response. Case N°2, 3 and 4: 7-year-old boy, 5-year-old boy and 1-year-8-month-old male infant, with X-recessive recessive Ichthyosis (IRLX) in treatment with NAC formula with good response. Case N°5: An 18-year-old woman with congenital ichthyosiform erythroderma (EIC) begins treatment with NAC formula but is discontinued because of poor tolerance. Case No. 6:3-year-old girl, with epidermolytic Ichthyosis (IE), starts treatment with NAC formula with poor tolerance and is also suspended. The effects of the NAC formula on different types of ichthyosis were evaluated, showing a good safety and efficacy profile in IL and IRLX, however, in EIC and IE, its use was restricted by adverse effects. Treatment with NAC formula has a good response and tolerance in patients with IL and IRLX, so it could be considered in the usual treatment of these patients.

Effect of N-acetylcysteine in hearts of rats submitted to controlled hemorrhagic shock / Efeito da N-acetilcisteína em corações de ratos submetidos ao choque hemorrágico controlado

Abstract Introduction: Pharmacological therapy is a strategy for the prevention of complications associated with ischemia and reperfusion injury that occurs after volume replacement in the treatment of hemorrhagic shock. Objective: The aim of this study was to evaluate the effect of N-acetylcysteine associated with fluid resuscitation in cardiac injury in a rat hemorrhagic shock model. Methods: Mice Wister male rats were randomly and subjected to controlled hemorrhagic shock for 60 min. and then, subjected to resuscitation with Ringer lactate. In a group of six animals, 150mg/kg of N-acetylcysteine were added to fluid volume replacement. The animals were observed for 120 min and after this period, were euthanized and cardiac tissue was collected for histopathological analysis and measurement of thiobarbituric acid reactive substances and pro-and anti-inflammatory interleukin. Results: Cardiac tissue of the group treated with N-acetylcysteine showed lower concentrations of thiobarbituric acid reactive substances (0.20±0.05 vs. 0.27±0.05, P=0.014) and reduced histopathological damage and edema when compared to the group whose volume replacement occurred only with Ringer lactate. There was no difference in the expression of cytokines interleukin 6 (2,138.29±316.89 vs. 1,870.16±303.68, P=0.091) and interleukin 10 (1.019,83±262,50 vs. 848.60±106.5, P=0.169) between the treated groups. Conclusion: The association of N-acetylcysteine on volume replacement attenuates oxidative stress in the heart, as well myocardial damage and edema, but does not modify the expression of inflammatory cytokines. .

Resumo Introdução: A terapia farmacológica é uma estratégia de prevenção das complicações associadas à lesão de isquemia e reperfusão tecidual que ocorre após a reposição volêmica no tratamento do choque hemorrágico. Objetivo: O objetivo deste estudo foi avaliar a repercussão da N-acetilcisteína associada à reposição volêmica na lesão cardíaca em modelo de choque hemorrágico em ratos. Métodos: Ratos Wistar, machos, foram randomizados e submetidos ao choque hemorrágico controlado por 60 minutos e, depois, submetidos à reposição volêmica com Ringer Lactato. Em um grupo de seis animais, foram adicionados 150 mg/Kg de N-acetilcisteína ao fluido de reposição volêmica. Os animais foram observados por 120 minutos e após este período foram submetidos à eutanásia e coleta do tecido cardíaco para análise histopatológica e dosagem de substâncias reativas ao ácido tiobarbitúrico e interleucinas pró e anti-inflamatórias. Resultados: Foi observada menor concentração de substâncias reativas ao ácido tiobarbitúrico (0,20±0,05 vs. 0,27±0,05, P=0,014) e menor dano histopatológico e edema no tecido cardíaco do grupo tratado com N-acetilcisteína em relação ao grupo cuja reposição volêmica ocorreu somente com Ringer Lactato. Não foi observada diferença da expressão das citocinas interleucina 6 (2.138,29±316,89 vs. 1.870,16±303,68, P=0,091) e interleucina 10 (1.019,83±262,50 vs. 848,60±106,5, P=0,169) entre os grupos tratados. Conclusão: A associação da N-acetilcisteína na reposição volêmica atenua o estresse oxidativo no coração, assim como dano e edema miocárdicos, porém, não modifica a expressão de citocinas inflamatórias. .

Diagnostic and Therapeutic Strategies for Severe Alcoholic Hepatitis / 대한소화기학회지

Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol abstinence is the sine qua non of therapy for AH and, in the milder forms, is prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure such as acute kidney injury and infection, which has a major impact on survival and thus should be closely monitored. Patients with severe ASH have a drastic short-term mortality of up to 40-50%. Specific therapies should be considered for patients with severe ASH at risk of early death. Corticosteroids are the standard of care for patients with severe ASH. When corticosteroids are contraindicated, pentoxifylline may be an alternative option. Steroid responsiveness should be evaluated on the basis of Lille score. Tactically, we should explore novel therapeutic targets to suppress inflammation based on cytokine profiles, promote hepatic regeneration, limit innate immune responses, and restore altered gut mucosal integrity in severe ASH.

A comparative study of pentoxifylline effects in adult and aged rats submitted to lung dysfunction by thermal injury

PURPOSE: To investigate the protective effects of pentoxifylline against lung injury observed after dorsal scald in aged animals. METHODS: Adult (eight months old) and aged (20 months old) rats were subjected to thermal injury or sham procedure. The six hours post-trauma animals received pentoxifylline and after 24 hours were euthanatized and lung tissue samples collectedted. The bronchoalveolar lavage fluid was evaluated for total protein content and tumor necrosis factor-alpha cytokine. Malondialdehyde and myeloperoxidase activety in the lung homogenate were measured and a histological lung examination was undertaken. RESULTS: Burn injury induced oxidative stress in lung homogenate was higher in elderly-burned rats compared to adult-burned rats (p<0.001). Total protein and cytokine in bronchoalveolar lavage increased in the elderly-burned group when compared to the adult-burned group (p<0.001). All parameters decreased in bolth groups treated with pentoxifylline (p<0.05). CONCLUSIONS: The injury was augmented in elderly rats when compared to adult rats. Damage was reduced with the use of pentoxifylline, however further studies are needed to evaluate the dose-response of the drug.

Effect of N-acetylcysteine on lung injury induced by skeletal muscle ischemia-reperfusion: histopathlogical study in rat model / Efeito de N-acetilcisteína em dano pulmonar induzido por isquemia-reperfusão de músculo esquelético: estudo histopatólogico em modelo de rato

PURPOSE: To investigate whether N-acetylcysteine, a free radicals scavenger has a protective effect against lung injury as a remote organ after skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I) and group ischemia-reperfusion + N-acetylcysteine (group II). All animals were undergone two hours of ischemia by occlusion femoral artery and 24h of reperfusion. Before clamped the femoral artery, 250 IU heparin was administered via the jugular vein to prevent clotting. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mgkg-¹, immediately before reperfusion. After 24h of reperfusion, animals were euthanized and left lung harvested for histopathological analysis under light microscopy. RESULTS: In the group I, tissues showed histological changes with intra-alveolar edema, intra-alveolar hemorrhage and neutrophilic infiltration. Histopathologically, there was a significant difference (P = 0.005) between two groups. CONCLUSION: Administration of N-acetylcysteine treatment significantly decreased lung injury induced by skeletal muscle ischemia reperfusion according to histological findings.

OBJETIVO: Investigar se N-acetilcisteína, neutralizador de radicais livres, tem efeito protetor contra dano pulmonar como um órgão remoto após isquemia-reperfusão de músculo esquelético. MÉTODOS: Vinte ratos machos Wistar, foram aleatóriamente distribuídos em dois grupos: grupo isquemia-reperfusão (grupo I) e grupo isquemia-reperfusão +N-acetilcisteína (grupo II). Todos os animais foram submetidos a duas horas de ischemia pela oclusão artéria femoral e 24 horas de reperfusão. Antes de ocluir a artéria femoral, foi administrado 250 IU de heparina pela veia jugular para prevenir coagulação. A N-acetilcisteína foi administrada por via intravenosa, na uma dose de 150 mgkg-1, imediatamente antes de reperfusão. Após 24 horas de reperfusão, os animais foram eutanasiados e o pulmão esquerdo foi removido para análise histológica em microscopia óptica. RESULTADOS: No grupo I, os tecidos mostraram alterações histológicas com edema e hemorragia intra-alveolar e infiltração neutrofílica. Houve diferença histopatológica significante (P = 0.005) entre os dois grupos. CONCLUSÃO: O tratamento com a N-acetilcisteína diminuiu significantemente o dano pulmonar induzido por isquemia-reperfusão de músculo esquelético.

Pretreatment with pentoxifylline attenuates lung injury induced by intestinal ischemia/reperfusion in rats / Pré-tratamento com pentoxifilina atenua a lesão pulmonar induzida por isquemia/reperfusão intestinal em ratos

PURPOSE: To investigate the protective effect of pentoxifylline against the lung injury observed after intestinal ischemia (I) followed by a period of reperfusion (R). METHODS: Twenty-eight male Wistar rats were equally divided into 4 experimental groups and operated under ketamine-xylazine anesthesia. (1) Sham: falsely-operated animals; (2) SS+IR: intestinal ischemia was accomplished by clipping the superior mesenteric artery during 60 minutes, with an administration of a standard volume of saline solution (SS) 5 min before the end of the ischemia period; the clip was then releases or a 120-min period of reperfusion; (3) I+PTX+R: ischemia as above, PTX was administered (25 mg/kg) and the gut reperfused as above; (4) PTX+I+PTX+R: Five minutes before arterial occlusion PTX was administered; the superior mesenteric artery was then clipped for 60 minutes. After 55-min ischemia, an additional dosis of PTX was administered; the clip was removed for reperfusion as above. At the 60th min of reperfusion a third dosis of PTX was administered. RESULTS: PTX markedly attenuated lung injury as manifested by significant decreases (all P<0.001 as compared with the SS+IR group) of pulmonary wet/dry tissue weight ratio, total protein content, myeloperoxidase activity and tumor necrosis factor-alpha. Moreover, it was apparent that in the group PTX+I+PTX+R the improvements have been even more significant. CONCLUSION: PTX exerted a protective effect on the lung from the injuries caused by intestinal ischemia/reperfusion.

OBJETIVO: Avaliar os efeitos protetores da pentoxifilina (PTX) na lesão pulmonar observada após isquemia (I) seguida de reperfusão (R) intestinal. MÉTODOS: Vinte e oito ratos machos foram divididos aleatoriamente em quatro grupos experimentais e operados sobre anestesia quetamina-xilazina. (1) Sham: animais falsamente operados; (2) SS+IR: isquemia intestinal realizada pelo clampeamento da artéria mesentérica superior durante 60 minutos, com a administração de solução salina (SS) 5 minutos antes do período de isquemia, após a retirada do clamp houve a reperfusão por mais 120 minutos; (3) I+PTX+R: isquemia como mencionado anteriormente seguida da administração de PTX (25 mg/Kg) 5 minutos antes do final da isquemia (60 minutos) seguida de reperfusão por mais 120 minutos; (4) PTX+I+PTX+R: 5 minutos antes da isquemia foi administrado PTX, após 55 minutos de isquemia foi administrado outra dose de PTX e a reperfusão mantida por mais 120 minutos, sendo que aos 60 minutos da reperfusão outra dose de PTX foi administrada. RESULTADOS: A pentoxifilina reduziu os marcadores de lesão pulmonar (proteínas totais, malondialdeído, atividade da mieloperoxidase e fator de necrose tumoral) quando comparada com o grupo não tratado (P<0.001), contudo esta redução foi mais significante no grupo PTX+I+PTX+R. CONCLUSÃO: A pentoxifilina exerce efeito protetor no pulmão no trauma causado por isquemia/reperfusão intestinal.

Pseudoporfiria induzida pela diálise tratada com N-acetilcisteína oral / Pseudoporphyria induced by dialysis treated with oral N-acetylcysteine

Pseudoporfiria é dermatose bolhosa rara, semelhante clínica e histopatologicamente à porfiria cutânea tardia. Acomete, principalmente, pacientes renais crônicos em diálise peritoneal ou hemodiálise. Medicamentos também podem ser envolvidos na etiologia. O diagnóstico e o manejo desta entidade é um desafio para os dermatologistas. Os autores demonstram um caso de pseudoporfiria, relacionada à diálise, com evolução favorável após o uso de N-acetilcisteína oral.

Pseudoporphyria is a rare bullous dermatosis that clinically and histopathologically is similar to porphyria cutanea tarda. It mainly affects patients with chronic renal failure on peritoneal dialysis or hemodialysis. Medications can also be involved in the etiology. Diagnosis and management of this condition is a challenge for dermatologists. The authors report a case of pseudoporphyria related to dialysis with favorable outcome after the use of oral N-acetylcysteine.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage / Efeito da N-acetilcisteína sobre o vasoespasmo na hemorragia subaracnóidea

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4 percent. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

O vasoespasmo arterial encefálico continua sendo uma complicação extremamente grave que acomete pacientes com hemorragia subaracnóidea (HSA) por ruptura de aneurismas. O arsenal terapêutico atual ainda, em muitos casos, é insuficiente e a busca de novas alternativas terapêuticas torna-se necessária. Neste estudo, avaliamos a ação da N-acetilcisteína (NAC) sobre o vasoespasmo arterial encefálico em um modelo experimental. Foram utilizados 24 ratos wistar divididos em 4 grupos: [1] Controle, [2] HSA, [3] HSA+NAC e [4] HSA+Placebo. O modelo experimental utilizado foi o da dupla injeção subaracnóidea de sangue autólogo. A dose proposta da NAC foi de 250 mg/kg/dia por via intraperitoneal. Foi analisada a área interna da artéria basilar para avaliação da ação da NAC. O modelo experimental mostrou-se excelente com mortalidade de 4 por cento. A mensuração da área interna da artéria basilar do grupo HSA demonstrou diminuição significativa em relação ao grupo controle (p=0,009). A administração da NAC reduziu significativamente o vasoespasmo em relação ao grupo não tratado (p=0,048) e estabeleceu diferença não significativa em relação ao grupo controle (p=0,098). Não houve melhora significativa com administração de placebo (P=0,97). O modelo da dupla hemorragia mostrou-se bastante útil para reprodução do vasoespasmo, com baixos índices de mortalidade. A administração da NAC diminuiu significativamente o vasoespasmo decorrente da HSA, podendo representar uma nova alternativa terapêutica.

Alterações pulmonares em um modelo de diabetes mellitus em ratos: o efeito da terapia antioxidante / Lung alterations in a rat model of diabetes mellitus: effects of antioxidant therapy

OBJETIVO: Avaliar as alterações estruturais no pulmão de ratos com diabetes mellitus (DM) através da quantificação do estresse oxidativo e do dano ao DNA, assim como determinar os efeitos de superóxido dismutase (SOD) exógena nessas alterações. MÉTODOS: Estudo experimental controlado com 40 ratos Wistar, divididos em quatro grupos (10 animais cada): grupo controle, grupo SOD (sem DM e tratados com SOD), grupo DM (com DM induzido por estreptozotocina), e grupo DM+SOD (com DM induzido por estreptozotocina e tratados com SOD). Os animais foram avaliados por um período de 60 dias, iniciado a partir do dia em que os animais com diabetes induzido por estreptozotocina apresentaram glicemia > 250 mg/dL. Nos últimos 7 dias do período, os animais nos grupos tratados receberam SOD. Ao final do tempo de estudo, amostras de tecido pulmonar foram coletadas para análise histopatológica e avaliação do estresse oxidativo e do dano ao DNA. RESULTADOS: Não houve diferenças significativas entre os grupos em relação ao dano ao DNA. Houve um aumento significativo na matriz extracelular e hiperplasia do endotélio capilar no grupo DM quando comparado com os grupos controle e SOD. Também houve mudanças significativas em pneumócitos tipo II e macrófagos intravasculares, sugerindo um processo inflamatório no grupo DM. Entretanto, uma redução na matriz extracelular, endotélio capilar normal e pneumócitos tipo II normais foram encontrados no grupo com DM+SOD. CONCLUSÕES: A administração exógena de SOD pode reverter alterações nos pulmões de animais com DM induzido.

OBJECTIVE: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD) has on such alterations. METHODS: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each): control; SOD-only (without DM but treated with SOD); IDM-only (with streptozotocininduced DM but untreated); and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were evaluated over a 60-day period, day 0 being defined as the day on which the streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was administered for the last 7 days of that period. At the end of the study period, samples of lung tissue were collected for histopathological analysis, evaluation of tissue oxidative stress, and assessment of DNA damage. RESULTS: There were no significant differences among the groups regarding DNA damage. In the IDM-only group, there was a significant increase in the extracellular matrix and significantly greater hyperplasia of the capillary endothelium than in the SOD-only and control groups. In addition, there were significant changes in type II pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only group. However, in the IDM+SOD group, there was a reduction in the extracellular matrix, as well as normalization of the capillary endothelium and of the type II pneumocytes. CONCLUSIONS: Exogenous SOD can reverse changes in the lungs of animals with induced DM.

Dimethylsulfoxide attenuates ischemia-reperfusion injury in rat testis / Dimetilsulfóxido atenua a lesão de isquemia-reperfusão em testículo de ratos

PURPOSE: To evaluate the protective role of dimethylsulfoxide (DMSO) in a rat model of testis ischemia/reperfusion (I/R). METHODS: Twenty-four male Wistar rats were randomized in two equal groups. Control rats (G-1) received saline 2.0 ml intraperitoneally (ip) 21, 9 and 1 h before torsion. Experimental rats (G-2) received ip injections of 3 percent aqueous solution of DMSO, 0.1ml/10g body weight. Saline was added to complete 2.0ml when necessary. I/R injury was induced in anesthetized rats by torsion of the right testis lasting 3 hours. Testis and blood samples were collected at the end of ischemia (T-0) and 3 hours later (T-3) for assessment of testis malonaldehyde (MDA), reduced glutathione (GSH), and plasma total antioxidant power (TAP). RESULTS: MDA levels decreased significantly in G-2 rats compared with G-1 animals in all time-points. GSH levels increased significantly in T-0 and T-3 time-points in DMSO pretreated rats compared with G-1 rats. GSH levels increased significantly during reperfusion in G-2 rats. TAP was similar in both groups denoting absence of systemic effects in this study. CONCLUSION: Pretreatment with DMSO reduces testis lipid peroxidation and oxidative stress caused by torsion/detorsion of the testis.

OBJETIVO: Avaliar o papel protetor do dimetilsulfóxido (DMSO) utilizando um modelo de isquemia/reperfusão (I/R) do testículo do rato. MÉTODOS: Vinte e quatro ratos machos Wistar, randomizados em dois grupos iguais e tratados com solução salina 2,0 ml (grupo Controle-G-1) ou solução de DMSO (3 por cento, 0,1ml/10g peso corporal), acrescida de solução salina até completar 2,0 ml (grupo Experimento-G-2) por via intraperitoneal, as 21, 9 e 1 h antes da torção. .A lesão de I/R foi induzida por torção do testículo direito e mantida por 3 horas, em ratos previamente anestesiados. Amostras (sangue e testículo direito) foram coletadas ao término da isquemia (T-0) e após 3 horas de reperfusão (T-3) para determinação das concentrações de malonaldeído (MDA), glutationa reduzida (GSH) e capacidade antioxidante total do plasma (CAT). RESULTADOS: As concentrações de MDA diminuíram significativamente nos ratos do G-2. comparados ao G-1, nos tempos estudados. As concentrações de GSH aumentaram significativamente nos testículos dos ratos do G-2 comparado aos controles no T-0 e no T-3 e durante a reperfusão no G-2. Os valores obtidos na análise do CAT foram semelhantes. CONCLUSÃO: O pré-tratamento com DMSO reduz a peroxidação lipídica e o estresse oxidativo decorrentes da torção/destorção do testículo, no rato.

Therapeutic role of L-arginine on free radical scavenging system in ischemic heart diseases.

Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina.

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats / Efecto protectivo del extracto de la hoja de Carica papaya L contra el daño gástrico agudo inducido por alcohol y el estrés oxidativo en ratas

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Los efectos de; extracto acuoso de la hoja de Carica papaya (CPL) en el daño gástrico agudo inducido por alcohol y el nivel de estrés oxidativo inmediato en la sangre, fueron estudiados en ratas. Los resultados mostraron que el índice de úlcera gástrica se reducía significativamente en ratas pre-tratadas con extracto de CPL, en comparación con los controles tratados con alcohol. Los estudios in vitro mediante el ensayo con 2,2-difenil-1-picrihidrazilo) mostraron la fuerte naturaleza antioxidante de extracto de CPL. El análisis bioquímico indicó que el daño agudo inducido por alcohol se refleja en las alteraciones de los índices oxidativos de la sangre y el extracto de CPL ofreció cierta protección con la reducción del nivel de peroxidación lipídica del plasma y el aumento de la actividad de la glutatión peroxidasa de los eritrocitos. La hoja de la Carica papaya puede servir potencialmente como un buen agente terapéutico para la protección contra la úlcera gástrica y el estrés oxidativo.

Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats / Papel da N-acetilcisteína na fibrose e estresse oxidativo em ratos cirróticos

BACKGROUND: Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis which is the main response to the liver injury. The inhalatory carbon tetrachloride is an effective experimental model that triggers cirrhosis and allows to obtain histological and physiological modifications similar to the one seen in humans. AIM: To investigate the effects of N-acetylcysteine (NAC) on the fibrosis and oxidative stress in the liver of cirrhotic rats, analyzing liver function tests, lipoperoxidation, activity of glutathione peroxidase enzyme, collagen quantification, histopathology, as well as the nitric oxide role. METHODS: The animals were randomly in three experimentals groups: control (CO); cirrhotic (CCl4) and CCl4 + NAC. Evaluate the lipid peroxidation, the glutathione peroxidase enzyme, the collagen and the expression of inducible nitric oxide synthase (iNOS). RESULTS: The cirrhotic group treated with N-acetylcysteine showed trough the histological analysis and collagen quantification lower degrees of fibrosis. This group has also shown less damage to the cellular membranes, less decrease on the glutathione peroxidase levels and less expression of inducible nitric oxide synthase when matched with the cirrhotic group without treatment. CONCLUSION: N-acetylcysteine seams to offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat livers.

RACIONAL: A cirrose é o estágio final da disfunção hepática, sendo caracterizada por fibrose difusa, que compõe a resposta principal do organismo ao dano hepático. O tetracloreto de carbono inalatório é um modelo experimental efetivo, que desencadeia a cirrose e permite obter modificações histológicas e fisiológicas similares às vistas em humanos. OBJETIVO: Investigar os efeitos da N-acetilcisteina (NAC) sobre a fibrose e o estresse oxidativo no fígado de ratos cirróticos, analisando as provas hepáticas, a lipoperoxidação, a atividade da enzima glutationa peroxidase, a quantificação do colágeno, a histopatologia, bem como o papel do óxido nítrico. MÉTODOS: Os animais foram divididos em três grupos experimentais: controle (CO); cirrótico (CCl4) e CCl4 + NAC. Foram avaliados a lipoperoxidação, a enzima glutationa peroxidase, a histologia hepática, a quantificação de colágeno e a expressão da óxido nítrico síntase induzível (iNOS). RESULTADOS: O grupo cirrótico tratado com a NAC demonstrou, através da análise histológica e da quantificação de colágeno, menores graus de fibrose. Este grupo demonstrou, ainda, menos dano às membranas celulares, menor decréscimo nos níveis de glutationa peroxidase e menor expressão da iNOS quando comparado com o grupo cirrótico sem tratamento. CONCLUSÃO: A NAC parece oferecer proteção contra a fibrose hepática e o estresse oxidativo no fígado de ratos cirróticos.

Radical scavenging activity of Trianthema triquetra in male albino rats intoxicated with CCl4.

Radical scavenging activity of ethanolic extract of Trianthema triquetra root was investigated against CCl4 in rats. The rats were treated with T. triquetra (100 mg, 200 mg/kg b.w.) for a period of 7 days. Antihepatotoxic effect was studied by assaying the activities of thiobarbituric acid (TBARS), reduced glutathione (GSH), glutathione peroxidase (GPx),catalase (CAT), super oxide dismutase (SOD) and vitamin C (Vit. C). Lipid peroxidation is evidenced by an increase in the value of TBARS and also a distinct diminution in the level of GSH, Vit. C at 200 mg/kg b.w. The activity of antioxidant enzymes, such as GPx, CAT SOD and Vit. E is significantly recovered towards an almost normal level in animals coadministrated with T. triquetra. The maximum protection against CCl4 induced hepatic injury was afforded by the dose of 200 mg/kg b.w. of Trianthema triquetra.

Attenuation of ischemia-reperfusion injury by ascorbic acid in the canine renal transplantation

This study examined the effects of ascorbic acid on the attenuation of an ischemia-reperfusion (I/R) injury after a canine renal transplantation. Eight beagle dogs were subjected to a renal auto-transplantation followed by the administration of ascorbic acid (treatment group) and the same amount of vehicle (physiological saline, control group). Blood samples were collected from these dogs to perform the kidney function tests and the invasive blood pressure was measured in the renal artery at pre- and post-anastomosis. The antioxidant enzymes of level 72 h after the transplant were measured. The kidneys were taken for a histopathology evaluation at day 21. The kidney function tests showed a significant difference between the control and treatment group. The invasive blood pressure in the renal artery was similar in the groups. The activity of the antioxidant enzymes in the blood plasma was significant lower in the control group than in the treatment group. The histopathology findings revealed the treatment group to have less damage than the control group. The results of this study suggest that ascorbic acid alone might play a role in attenuating I/R injury and assist in the recovery of the renal function in a renal transplantation model.

Paraparesia espástica tropical: a propósito de un caso clínico / Tropical spastic paraparesis: report of a case

Se presenta el caso clínico de una paciente con diagnóstico inicial de hipotiroidismo, cuadro que ameritó internación, compensado adecuadamente con levotiroxina. A pesar de existir buena respuesta al tratamiento instaurado, persiste la presencia de sintomatología de compromiso neurológico por lo que se solicita evaluación por dicha especialidad; se encuentran datos sugestivos de un cuadro de paraparesia espástica tropical, enfermedad producida por el HTVLI. El diagnóstico es confirmado mediante examenes de laboratorio. Es tratada con pentoxifilina y vitamina C con respuesta clínica inicial buena, pero posteriormente presenta exacerbación de las manifestaciones neurológicas, como sucede habitualmente en esta patología. nuestro país se encuentra en una regíon endemica de la infección mencionada, y sin embargo el diagnóstico es mas bien esporádico. Se discute en este artículo la epidemiología, las dificultades diagnósticas que planteo este caso en particular y las posibilidades terapéuticas de esta enfermedad neurológica.

We present the case of a female patient who initially was diagnosed with hypothyroidism, and adequately compensated with levotiroxin . In spite of the otherwise successfultreatment, neurological symptoms persisted. The neurological examination showed datasuggestive of tropical spastic paraparesis,a disease caused by HTVL-1.The diagnosis was confirmed by laboratory tests. The patient was treated with pentoxifiline and vitamin C, initially with a good clinical response. Later on, however, exacerbation of the neurological symptoms resulted, as usually happens in this disease. In our country, tropical spastic paraparesis is endemic but only sporadically diagnosed. We review the most relevant aspects of epidemiology, the diagnostic difficulty in this case, and the therapeutic options for this neurological disease.