Potentiation of carbon-tetrachloride hepato-nephrotoxicity by phenobarbital in man, a case report

A 47 year-old male epileptic who had been treated for eight years with variable doses of phenobarbital and valproate was hospitalized in the intensive care unit with the following clinical and biological features: coma grade 2, metabolic acidosis, acute renal and hepatic failure. The recent clinical history revealed that he had been using CCl4 to clean paintings for the last three days in a confined atmosphere. Upon admission, the recent absorption of CCl4 was confirmed by the detection of the solvent in blood and adipose tissue. Cellular lipoperoxidation was suggested by the presence of an increased concentration of pentane in expired air. Evidence of microsomal enzyme induction was provided by the relative preservation of aminopyrine demethylation as indicated by the 14C-aminopyrine breath test and also by the morphological evidence of endoplasmic reticulum proliferation at liver biopsy. Supportive therapy, repeated haemodialysis and administration of antioxidant drugs resulted in a complete recovery. The unusual severity of CCl4-induced liver and renal injury observed in this case is best explained by the induction of CCl4 microsomal activation due to phenobarbital therapy.