Decreased acute hepatotoxicity of carbon tetrachloride and bromobenzene by cholestyramine in the rat.
Numerous factors are known to increase or decrease drug-induced liver injury. The aim of this study was to test the effect of cholestyramine. Cholestyramine, and anion exchange resin binding in the gut substances taken up and metabolized by the liver such as bile salts, vitamins, endotoxins, etc., could indirectly modify drug-induced toxicity. Two groups of animals were studied: cholestyramine-fed and pair-fed controls. Five days after feeding, carbon tetrachloride or corn oil was injected intraperitoneally. Liver function and histology were normal after corn oil injection in both groups. One day after carbon tetrachloride injection liver weight/body weight ratio was lower in the cholestyramine-fed than in the pair-fed group (4.0 +/- 0.4 mean +/- SD vs. 4.4 +/- 0.3, p less than 0.05). Alanine and aspartate aminotransferases were lower (618 +/- 782 IU and 242 +/- 147 IU vs. 8245 +/- 8189 and 1966 +/- 1524 IU, p less than 0.001), as was necrosis (p less than 0.05). Steatosis and inflammatory reaction were similar in both groups. Two and four days later there were no significant differences between the two groups, because necrosis was no longer a major feature in the pair-fed group. Similar experiments were performed with bromobenzene. Here too cholestyramine prevents necrosis but to a much lesser extent. These results confirm that steatosis and necrosis are independent toxic effects of carbon tetrachloride. Cholestyramine, a widely used drug in cholestasis, could provide a potentially clinically important hepatocellular resistance to toxicity from environmental agents.
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D001969:Bromobenzenes / Q000506:poisoning; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury; D002792:Cholestyramine Resin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D051381:Rats
D001969:Bromobenzenes; D002792:Cholestyramine Resin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase