INDUCTION OF PARACETAMOL BIOTRANSFORMATION IN THE RAT-LIVER BY GAMMA-HEXACHLOROCYCLOHEXANE

The effect of the insecticide gamma-hexachlorocyclohexane (lindane), a compound which induces the synthesis of hepatic microsomal enzymes, o n the metabolism of paracetamol was investigated in the isolated perfu sed rat liver. Male Wistar rats were treated with gamma-hexachlorocycl ohexane (200, 400 and 800 ppm) in the drinking water for 2 weeks. When 1.0 mM paracetamol was recirculated in liver perfusion experiments (v olume = 140 ml, flow = 34 ml/min), the initial rate of uptake increase d from 270 nmol min(-1) g(-1) (control) to 435 nmol min(-1) g(-1) (200 ppm), 575 nmol nmol min(-1) g(-1) (400 ppm) and 648 nmol min(-1) g(-1 ) (800 ppm). The increased rates of uptake of paracetamol in livers fr om rats treated with gamma-hexachlorocyclohexane were probably due to the activation of mixed function oxidases. The mixed function oxidases are believed to be responsible for the formation of the toxic interme diate of paracetamol metabolism, which produces necrosis of the hepati c tissue. In consequence, one can expect that humans, chronically expo sed to gamma-hexachloro-cyclohexane or similar insecticides and pestic ides, are much more susceptible to liver damage when using paracetamol as a pain reliever.