alpha-lipoic acid protects against acetaminophen-induced hepatotoxicity: inhibition of FAS mediated liver apoptosis

Acetaminophen [APAP] overdose causes acute liver injury in humans and animals. This study was carried out to investigate whether the lipid soluble antioxidant -lipoic acid [ALA] can protect against APAP-induced hepatotoxicity. Rats were treated with APAP [1q/kg] I.P. either alone or with ALA [100mg/ kg] at the same time for 24hr. Acetaminophen caused a time-dependent increase in the plasma levels of ALT enzyme activity; hepatocytes LDH leakage; nitric oxide [measured as NO2 -/NO3-] levels and caused severe hepatic necrosis. It also decreased liver contents of reduced glutathione [GSH]. In addition, APAP caused hepatic DNA fragmentation as assessed by agarose gel electrophoresis technique; increased apoptotic index [assessed by TUNEL assay] and liver Fas expression [assessed immunohistochemically]. Co-administration of ALA with APAP resulted in protection against APAP-induced hepatic injury as presented by the significant decrease in the hepatocellular enzyme release [ALT and LDH] and attenuation of hepatocytes apoptosis and necrosis. The hepatoprotective effect of ALA against APAP-induced liver damage was found to be due to several mechanisms including attenuation of hepatic lipid peroxidation [measured as MDA], increase hepatic contents of GSH, and/or decrease liver Fas expression, decreased apoptotic cell death and DNA damage. These results may recommend the use of ALA in treatment of APAP-induced hepatotoxicity as a new line therapy

Potential renoprotective effects of Ramipril and vitamin E in streptozotocin - induced diabetic male albino rats

Hyperglycemia, a well recognized pathogenic factor of long-term complications in diabetes mellitus, not only generates more reactive oxygen species but also attenuates antioxidative mechanisms. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. Tumor necrosis factor-alpha [TNF-alpha] has been implicated as a link between insulin resistance, diabetes and endothelial dysfunction. The present study was undertaken to investigate whether treatment of streptozotocin-induced diabetic rats with a combination therapy of angiotensin converting enzyme inhibitor [ramipril] and vitamin E reduce the possible hazards of oxidative damage induced by reactive oxygen species. Forty male adult albino rats divided into 5 groups each included 8 rats and arranged as control group, streptozotocin-induced diabetic group [60 mg/kg b.wt.i.p.], ramipril + diabetic group, vitamin E + diabetic group and ramipril + vitamin E + diabetic group. Ramipril was given in a dose of 10