The acute toxic action of dimethylnitrosamine on liver cells

Abstract

LongdashThe acute hepatotoxic action of dimethylnitrosamine was investigated with homogenates and mitochondrial preparations from the livers of rats injected with 100 mg/kg body weight at various times between 8 and 24 hours before killing. Aerobic oxidation of pyruvate, octanoate, L-malate, citrate, L-glutamate, a-oxo-glutarate and B-hydroxybutyrate progressively decreased after the 12th hour and was grossly reduced by the 20th hour. Aerobic oxidation of choline was only slightly reduced. Succinoxidase activity and anaerobic glycolysis were unaffected even when necrosis was extensive. Oxygen uptakes of the diphosphopyridine nucleotide-linked systems could be greatly raised by the addition of diphosphopyridine nucleotide to the mitochondrial incubation medium. No other cofactor tested was effective. Dimethylnitrosamine did not show an effect in vitro on normal rat-liver homogenate. Ethylenediaminetetra-acetic acid did not reverse the inhibition of aerobic oxidation of mitochondrial preparations made 16 hours after poisoning.