Liver damage in acute heliotrine poisoning. 2. The effect of nicotinamide on pyridine nucleotide concentrations

Mechanisms Involved in the ‘Dying‐back’ Process—an Hypothesis Implicating Coenzymes

“…It is known, too, that there is an increase in urinary excretion of N-1-methyl nicotinamide after giving azaserine (Narrod et al., 1959), dimethyl nitrosamine and other alkylating agents (Chu & Lawley, 1975). It has even been reported tha.t a degree of protection occurs against the lowering of NAD coenzymes, and in some cases against liver necrosis, by giving large doses of nicotinamide (Christie & Le Page, 1962;Schein, Cooney & Vernon, 1967;Rakieten et al, 1971). Bederka et al (1975) have also speculated in a different context about the mechanism of toxicity of various drugs in relation to the changes induced by these in the turnover of the nicotinamide dinucleotide pool.…”

Acute toxic liver injury. nicotinamide-adenine dinucleotide-pyrophosphorylase activity of nuclei isolated from rat liver in heliotrine and in dimethylnitrosamine poisoning

“…The concentrations of liver NAD 4 hr. after injection of nicotinamide were also depressed in rats pretreated with heliotrine (Christie & Le Page, 1962b). The present observations complement these studies and show No.…”

“…(Bailie, 1959; M. J. Baflie, G. S. Christie & R. N. Le Page, unpublished work). Also the capacity of the liver to synthesize NAD in vivo in 'response' to a single large dose of nicotinamide appeared to decrease with increasing duration of pretreatment of the rats with heliotrine (Christie & Le Page, 1962b); the possibility remained, however, that the apparent decrease of synthesis was not real but arose from losses of liver coenzymes which were known to be occurring. It seemed that measurements of the NAD-pyrophosphorylase activity of nuclei isolated from the livers of rats poisoned with heliotrine or with dimethylnitros-amine might help to show whether a real interference with NAD synthesis occurred.…”