Liver nucleotides in acute experimental liver injury induced by dimethylnitrosamine and by thioacetamide

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Abstract
The concentrations of the nicotlnamideadenine dinucleotides in rat liver have been determined at intervals during the period 1-24 hr. after feeding adult female rats with dimethylnitrosamine or thioacetamide. The administration of dimethylnitrosamine resulted in a rapid decrease in the sum of NAD [nicotinamide adenlne dinucleotide]+NADH2 [reduced nicotinamide adenine dinucleotide]. This sum was decreased by 40% 3 hr. after dosing. Dimethyl-nitrosamlne administration also produced an overall decrease in the NADP [nicotinamide adenine dlnucleotide phosphate ]+NADPH2 [reduced nicotinamide adenine dinculeotide phosphate] but this decrease was not so early nor as marked as that found for NAD+NADH2. The changes produced by thioacetamide were quite different from those obtained with dimethylnitrosamine. Thioacetamide produced a temporary rise in the NAD+NADH2 followed by a small drop. The NADP+NADPH2 was little changed in the early hours after dosing with thioacetamide but had decreased by approx. 15% 18 hr. after administration. These changes are discussed in terms of the known hepatotoxic actions of dimethylnitrosamine and thioacetamide, and are compared with previously reported changes found after the administration of carbon tetrachloride.