The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage.
The potential protective role of alpha-lipoic acid (alpha-LA) in acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity was investigated in rats. Pretreatment of rats with alpha-LA (100mg/kg) orally protected markedly against hepatotoxicity and nephrotoxicity induced by an acute oral toxic dose of APAP (2.5 g/kg) as assessed by biochemical measurements and by histopathological examination. None of alpha-LA pretreated animals died by the acute toxic dose of APAP. Concomitantly, APAP-induced profound elevation of nitric oxide (NO) production and oxidative stress, as evidenced by increasing of lipid peroxidation level, reducing of glutathione peroxidase (GSH-Px) activity and depleting of intracellular reduced glutathione (GSH) level in liver and kidney, were suppressed by pretreatment with alpha-LA. Similarly, daily treatment of rats with a smaller dose of alpha-LA (25mg/kg) concurrently with a smaller toxic dose of APAP (750 mg/kg) for 1 week protected against APAP-induced hepatotoxicity and nephrotoxicity. This treatment also completely prevented APAP-induced mortality and markedly inhibited APAP-induced NO overproduction and oxidative stress in hepatic and renal tissues. These results provide evidence that inhibition of NO overproduction and maintenance of intracellular antioxidant status may play a pivotal role in the protective effects of alpha-LA against APAP-induced hepatic and renal damage.
Abdel-Zaher
Ahmed O
AO
Department of Pharmacolog, Faculty of Medicine, Assiut University, Assiut, Egypt. ahmedosmanaz@hotmail.com
Abdel-Hady
Randa H
RH
Mahmoud
Madeha M
MM
Farrag
Magda M Y
MM
D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D001806:Blood Urea Nitrogen; D056486:Chemical and Drug Induced Liver Injury; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D009573:Nitrites / Q000097:blood; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D009573:Nitrites; D020011:Protective Agents; D000082:Acetaminophen; D008063:Thioctic Acid; D003404:Creatinine; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase