Neuroprotective effect of nitric oxide donor isosorbide-dinitrate against oxidative stress induced by ethidium bromide in rat brain

This study investigated the effect of systemic administration of isosorbide-dinitrate (ISDN) on oxidative stress and brain monoamines in a toxic model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide (10 μl of 0.1 %). Rats received saline (control) or ISDN at 5 or 10 mg/kg for 10 days prior to injection of ethidium bromide. Rats were euthanized one day later, and then the levels of reduced glutathione (GSH), lipid peroxidation (malondialdehyde; MDA), nitric oxide (nitrite/nitrate), acetylcholinesterase (AChE) activity, paraoxonase activity as well as monoamine levels (serotonin, dopamine and noradrenaline) were assessed in the brain cortex in different treatment groups. The i.c.i of ethidium bromide resulted in increased oxidative stress in the cortex one day after its injection; (i) MDA increased by 36.9 %; (ii) GSH decreased by 20.8 %, while (iii) nitric oxide increased by 60.3 %; (iv) AChE and paraoxonase activities in cortex decreased by 35.9 % and 29.4 %, respectively; (v) serotonin was significantly increased. In ethidium bromide-treated rats, pretreatment with ISDN at 10 mg/kg decreased cortical MDA by 23.9 %. Reduced glutathione was increased by 25.1 % ISDN at 10 mg/kg, while nitric oxide showed a 32.8 and 41.7 % decrease after 5 and 10 mg/kg of ISDN, respectively. Acetylcholinesterase activity increased by 24.3 % by 10 mg/kg of ISDN. Paraoxonase activity showed further decrease by 72.2 and 83.8 % after treatment with 5 and 10 mg/kg of ISDN, respectively. The administration of ISDN decreased the level of serotonin and noradrenaline compared with the ethidium bromide only treated group. Overall, the present findings suggest neuroprotective effect of ISDN against oxidative stress in this model of chemical demyelination

Aged garlic extract enhances paraoxonase 1 activity and suppress oxidative stress in CCl4

O presente estudo foi realizado para avaliar o potencial hepatoprotetor do extrato de alho envelhecido (AGE) contra hepatotoxicidade induzida por CCl4 em ratos machos adultos. CCl4 intoxicação (1ml/Kg no peso corporal, duas vezes por semana, ip durante 4 semanas) aumentou significativamente o Estresse oxidativo, tal como indicado pelo aumento da formação de MDA hepática, diminuição tanto de soro total e conteúdo de glutationa, e inibição da atividade de glutationa redutase hepática e paraoxonase soro 1 (POX1 ). Além disso, o tratamento com CCl4 produziu um aumento significativo nas atividades séricas de ALT, AST e nível de albumina com uma diminuição significativa no nível de proteína total. Ademais, o tratamento com CCl4 resultou num aumento significativo dos níveis de colesterol total, colesterol-LDL, triglicerídeos, bem como isoenzima creatina quinase e atividades da lactato desidrogenase, e uma diminuição significativa nos níveis de HDL-colesterol, se comparado com o grupo controle. O tratamento oral com AGE em doses de 100 e 200 mg / kg / dia em combinação com CCl4 demonstrou melhoras significativas na gravidade das alterações de CCl4 induzidas nos parâmetros acima mencionados, de uma maneira dose-dependente. Em conclusão, o presente estudo indicou que a idade aumenta a atividade de POX1 e atenua a disfunção no fígado e no coração induzidas por CCl4. Os efeitos protetores de idade contra a CCl4 toxicidade podem ser atribuídos aos seus antioxidantes e radicais livres, devido aos elevados teores de compostos organosulfurados.The current study was undertaken to evaluate the hepatoprotective potential of aged garlic extract (AGE) against hepatotoxicity induced by CCl4 in adult male rats. CCl4 intoxication (1ml/ kg b.w., twice a week, i.p. for 4 weeks) significantly increased oxidative stress as indicated by increased hepatic MDA formation, decreased both serum total and reduced glutathione contents, and inhibition of hepatic glutathione reductase and serum paraoxonase 1(POX1) activities. In addition, treatment with CCl4 produced a significant increase in the activities of serum ALT, AST and albumin level with a significant decrease in total protein level. Moreover, treatment with CCl4 resulted in significant increase in the levels of total cholesterol, LDL-cholesterol, triglycerides as well as creatine kinase isoenzyme and lactate dehydrogenase activities, and a significant decrease in HDL-cholesterol compared to control group. Oral treatment with AGE at doses of 100 and 200 mg/ kg/day in combination with CCl4 significantly ameliorated the severity of CCl4- induced changes in the above mentioned parameters in a dose- dependent manner. In conclusion, the present study indicated that AGE improves POX1 activity and attenuates liver and cardiac dysfunction induced by CCl4. The protective effects of AGE against CCl4 toxicity may be attributed to its antioxidant and free radical scavenging activities due to its higher contents of organosulphur compounds

Extrato envelhecido de alho incrementa a atividade de paraoxonase 1 e suprime o estresse oxidativo em ratos intoxicados com CCl4 -

The current study was undertaken to evaluate the hepatoprotective potential of aged garlicextract (AGE) against hepatotoxicity induced by CCl4 in adult male rats. CCl4 intoxication (1ml/kg b.w., twice a week, i.p. for 4 weeks) significantly increased oxidative stress as indicated byincreased hepatic MDA formation, decreased both serum total and reduced glutathione contents,and inhibition of hepatic glutathione reductase and serum paraoxonase 1(POX1) activities. Inaddition, treatment with CCl4 produced a significant increase in the activities of serum ALT, ASTand albumin level with a significant decrease in total protein level. Moreover, treatment with CCl4resulted in significant increase in the levels of total cholesterol, LDL-cholesterol, triglycerides as wellas creatine kinase isoenzyme and lactate dehydrogenase activities, and a significant decrease inHDL-cholesterol compared to control group. Oral treatment with AGE at doses of 100 and 200 mg/kg/day in combination with CCl4 significantly ameliorated the severity of CCl4- induced changes inthe above mentioned parameters in a dose- dependent manner. In conclusion, the present studyindicated that AGE improves POX1 activity and attenuates liver and cardiac dysfunction inducedby CCl4. The protective effects of AGE against CCl4 toxicity may be attributed to its antioxidant andfree radical scavenging activities due to its higher contents of organosulphur compounds.O presente estudo foi realizado para avaliar o potencial hepatoprotetor do extrato de alhoenvelhecido (AGE) contra hepatotoxicidade induzida por CCl4 em ratos machos adultos. CCl4intoxicação (1ml/Kg no peso corporal, duas vezes por semana, ip durante 4 semanas) aumentousignificativamente o Estresse oxidativo, tal como indicado pelo aumento da formação de MDAhepática, diminuição tanto de soro total e conteúdo de glutationa, e inibição da atividade deglutationa redutase hepática e paraoxonase soro 1 (POX1 ). Além disso, o tratamento com CCl4produziu um aumento significativo nas atividades séricas de ALT, AST e nível de albumina comuma diminuição significativa no nível de proteína total. Ademais, o tratamento com CCl4 resultounum aumento significativo dos níveis de colesterol total, colesterol-LDL, triglicerídeos, bem comoisoenzima creatina quinase e atividades da lactato desidrogenase, e uma diminuição significativanos níveis de HDL-colesterol, se comparado com o grupo controle. O tratamento oral com AGE emdoses de 100 e 200 mg / kg / dia em combinação com CCl4 demonstrou melhoras significativas nagravidade das alterações de CCl4 induzidas nos parâmetros acima mencionados, de uma maneiradose-dependente. Em conclusão, o presente estudo indicou que a idade aumenta a atividadede POX1 e atenua a disfunção no fígado e no coração induzidas por CCl4. Os efeitos protetoresde idade contra a CCl4 toxicidade podem ser atribuídos aos seus antioxidantes e radicais livres,devido aos elevados teores de compostos organosulfurados