Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.
Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India.
Varghese V
VV
Mathews
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India.
Mv Sauganth
MS
Paul
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India.
M
M
Abhilash
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India.
Alex
A
Manju
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India.
S
S
Abhilash
Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, P.D Hills, Kottayam, Kerala, India harinairsbs@gmail.com.
R Harikumaran
RH
Nair
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010087:Oxides / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D001152:Arsenicals; D015525:Fatty Acids, Omega-3; D010087:Oxides; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D000077237:Arsenic Trioxide