INHIBITION OF CARBON TETRACHLORIDE-INDUCED LIVER-INJURY IN ACATALASEMIC MICE BY HEPATIC IRON DEPRIVATION

We have demonstrated an enhanced liver injury in the later phases (aft er 12 h) of carbon tetrachloride (CCl4) intoxication in acatalasemic m ice, which was considered to be attributed to the increased formation of hydrogen peroxide (H2O2) or hydroxyl radicals (degrees OH) in the a bsence of catalase. The present study was attempted to investigate the effects of hepatic iron deprivation on CCl4-induced hepatotoxicity in acatalasemic mice. Hepatic iron deprivation was induced by phlebotomy , subcutaneous injection of erythropoietin, and intraperitoneal inject ion of the iron-chelating agent DFO. CCl4 was injected intraperitoneal ly on the fourth day of the treatment. By the iron deprivation, the he patic iron concentrations (HICS) of both acatalasemic and normal mice were decreased below half the iron-undeprived levels. In the iron-defi cient CCl4-treated mice, the increases of serum alanine aminotransfera se (ALT) activity and the liver thiobarbituric acid reactive substance (TBARS) level 18 h after CCl4 treatment were suppressed in both acata lasemic and normal mice, the difference in serum ALT level between aca talasemic and normal mice became insignificant, and the extent of the centrilobular necrosis was also histologically attenuated, resulting i n the disappearance of the difference in the extent of hepatocellular necrosis between them. Analysis of the results by ANOVA indicated that both the catalase levels and iron levels were related to the differen ce in the extent of CCl4-induced liver damage. We conclude that CCl4-i nduced hepatotoxicity in the later phases is likely to be produced thr ough the formation of H2O2 or degrees OH formed from H2O2 in which iro n is important in mediating its toxicity, and catalase plays a critica l role in the prevention of CCl4-induced secondary hepatotoxicity. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.