Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

✍ Scribed by Cristina W. Nogueira; Lysandro Pinto Borges; Ana Cristina Guerra Souza

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 724 KB
• Volume: 29
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1394

✦ Synopsis

Carbon tetrachloride (CCl 4 ) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl 4 -induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe) 2 , on hepatotoxicity induced by CCl 4 in rats. To this end, male Wistar rats received (PhSe) 2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl 4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (d-ALA-D) activity]. Repeated administration of (PhSe) 2 caused a marked potentiation of hepatotoxicity induced by CCl 4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe) 2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe) 2 prevented animal death, suggesting an activator action of (PhSe) 2 in CYPs. This study clearly indicates that (PhSe) 2 potentiated acute hepatic damage induced by CCl 4 .