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

• Published in: Journal of applied toxicology Vol. 29; no. 2; pp. 156 - 164
• Main Authors: Nogueira, Cristina W., Borges, Lysandro Pinto, Souza, Ana Cristina Guerra
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-03-2009; Wiley
• Subjects: Administration, Oral; Alanine Transaminase - blood; Animals; Ascorbic Acid - analysis; Ascorbic Acid - metabolism; Aspartate Aminotransferases - blood; Benzene Derivatives - administration & dosage; Benzene Derivatives - pharmacology; Bilirubin - blood; Biological and medical sciences; carbon tetrachloride; Carbon Tetrachloride - toxicity; Carbon Tetrachloride Poisoning - metabolism; Carbon Tetrachloride Poisoning - pathology; Catalase - analysis; Catalase - metabolism; Creatinine - analysis; diphenyl diselenide; Drug Synergism; Drug-Related Side Effects and Adverse Reactions - metabolism; Drug-Related Side Effects and Adverse Reactions - pathology; gamma-Glutamyltransferase - blood; hepatotoxicity; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Medical sciences; Organoselenium Compounds - administration & dosage; Organoselenium Compounds - pharmacology; oxidative damage; Porphobilinogen Synthase - analysis; Porphobilinogen Synthase - metabolism; Rats; Rats, Wistar; selenium; Thiobarbituric Acid Reactive Substances - analysis; Thiobarbituric Acid Reactive Substances - metabolism; Toxicology; Urea - blood; Oxidative stress; Rat; diphenyl diselenide; Digestive system; Toxicity; Liver; Carbon tetrachloride; Rodentia; Oral administration; Hepatic disease; oxidative damage; Micronutrient; Vertebrata; Mammalia; Animal; hepatotoxicity; Digestive diseases; Selenium
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1394

Carbon tetrachloride (CCl4) 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 CCl4‐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 CCl4 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 CCl4 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 (δ‐ALA‐D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 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 CCl4. Copyright © 2008 John Wiley & Sons, Ltd.
Carbon tetrachloride (CCl4) 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 CCl4‐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 CCl4 in rats.