Long-Term Perturbation of Pyridine Nucleotides in Rat Liver

Abstract

1) During a treatment of rats with 4 mmol of nicotinamide per kg body weight daily at 12-h intervals for several weeks a permanent rise of liver NAD by several hundred percent is effected; NADP® + NADPH also increase slightly. 2) Male and female animals of the SIV-50 strain differ in normal and in elevated NAD® values; female rats react more markedly and present more pronounced alterations of the liver. 3) Besides nicotinamide, large amounts of " 1methylnicotinamide and nicotinuric acid, and also small amounts of nicotinamide TV-oxide are excreted into the urine. Nicotinuric acid, an unexpected metabolite, was crystallized from urine and identified unequivocally. 4) A permanent load of rats with l g nicotinamide per kg body weight daily leads to alterations of the liver which manifest themselves macroscopically, by hepatocyte enlargement, glycogen deposits, enzyme decreases, and eventually fatty degeneration. When extra methionine and glycine are given in the diet, liver alterations are much less severe. It is concluded that the treatment with nicotinamide causes a severe amino acid imbalance. 5) During the treatment, animals show symptoms of catatonic stupor which is discussed in connection with proposals of a nicotinamide megatherapy against schizophrenia. On the whole, the experimental system of permanently elevated NAD® concentrations is combined with rather serious disadvantages; it is not regarded as a very good general model in studies of liver NAD®.