ACTION OF VITAMIN C AGAINST ACETAMINOPHEN-INDUCED HEPATORENAL TOXICITY IN RATS

Abstract

Effects of different doses of vitamin C against acetaminophen (APAP)-induced hepatorenal toxicity was investigated in male rats. The experimental groups included, a control group which received vehicle, a group intraperitoneally injected with a single dose of vitamin C (320 mg/kg body weight (b.wt.)), a group which received an oral overdose of APAP (1 g / kg b.wt.), as well as three groups administered the APAP overdose followed by a single dose of vitamin C (80, 160 or 320 mg/kg b.wt). All animals were watched for 24 hours, after which the mortality rate and serum levels of the hepatorenal indices were measured. Liver glutathione level and the ultrastructure of hepatic and renal tissues were also studied. Administration of APAP overdose induced a high mortality rate and hepatorenal toxicity as indicated by significantly higher levels of hepatorenal indices and decreased liver glutathione. It also caused cellular alterations and necrosis of hepatocytes and some renal cortical cells. However, injection of vitamin C alone caused no abnormalities. The injection of vitamin C after APAP administration decreased the hepatorenal toxicity in a dose-dependent manner. The highest dose of vitamin C normalized the levels of liver glutathione and serum hepatorenal indices except for bilirubin. It also protected hepatic and renal cells except for slight dilatation of rough endoplasmic reticulum and glycogen depletion in some hepatocytes, as well as the presence of lysosomal structures in cortical tubular epithelia. No fatalities were seen in rats treated with the highest two doses of vitamin C. It could be concluded that the highest dose of vitamin C prevented against the lethal effect of APAP overdose, although it incompletely protected against hepatorenal toxicity.