The protective effect of N-acetylcysteine against cyclosporine A-induced hepatotoxicity in rats.
The immunosuppressive agent cyclosporine A (CsA) has been reported to exert measurable hepatotoxic effects. One of the causes leading to hepatotoxicity is thought to be reactive oxygen radical formation. The aim of this study was to investigate the effects of N-acetylcysteine (NAC) treatment on CsA-induced hepatic damage by both analysing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), aspartate aminotransferase (AST) and alanine transaminase (ALT) activities with malondialdehyde (MDA) and nitric oxide (NO) levels, and using an histological approach. CsA administration produced a decrease in hepatic SOD activity, and co-administration of NAC with CsA resulted in an increase in SOD activity. MDA and NO levels increased in the CsA group and NAC treatment prevented those increases. A significant elevation in serum AST and ALT activities was observed in the CsA group, and when NAC and CsA were co-administered, the activities of AST and ALT were close to the control levels. CsA treatment caused evident morphological alterations. Control rats showed no abnormality in the cytoarchitecture of the hepatic parenchyma. The co-administration of NAC with CsA showed no signs of alteration and the morphological pattern was almost similar to the control group. In conclusion, CsA induced liver injury and NAC treatment prevented the toxic side effects induced by CsA administration through the antioxidant and radical scavenging effects of NAC.
Kaya
Hasan
H
Department of Internal Medicine, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.
Koc
Ahmet
A
Sogut
Sadik
S
Duru
Mehmet
M
Yilmaz
H Ramazan
HR
Uz
Efkan
E
Durgut
Ramazan
R
D000111:Acetylcysteine / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D016572:Cyclosporine; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D009569:Nitric Oxide; D008315:Malondialdehyde; D016572:Cyclosporine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine