Release of cholinesterase from rat liver by nicotinamide and carbon tetrachloride

Influence of carbon tetrachloride (CCl4) and nicotinamide (NA) on the concentration of cholinesterase (ChE) in liver and plasma was studied in normal and ethyl-p-nitrophenyl thiobenzene phosphonate (EPN)-treatedfemale rats.The enzyme was assayed by the Warburg manometric technique using propionylcholine iodide as the substrate. The ChE content of liver declined by about 80 per cent in 18 hr after oral administration of CCl4 (1.25 ml/kg body wt.) to normal rats. The plasma ChE levels increased substantially within 8 hr, but then declined rapidly to reach the basal values within a 24-hr period. NA failed to prevent the CCl4-induced release of ChE from liver at doses (500 mg/kg body wt., i.p. twice at 8-hr intervals) known to be effective against the hepatotoxic action of CCl4. Instead, it caused about 50 per cent reduction in the ChE content of liver with the consequent elevation of the plasma enzymic levels. These effects were dose related and reversible. The decline in plasma ChE activity subsequent to EPN treatment was significantly less in NA-treated animals and almost negligible in CCl4-treated ones. NA had no effect in vitro on ChE activity, nor did it reactivate the enzyme inhibited in vivo as a result of EPN administration. The protective effect of NA was characterized by a 2- to 3-fold increase in the ld50 value and some prolongation of the survival time; whereas, CCl4, while failing to influence the ld50 value, exerted greater effect on the survival time.