A novel sodium benzoate analog (CH-1) decreases blood ammonia levels in experimental hyperammonemia

Sodium benzoate has been used for the treatment of congenital hyperammonemic syndromes and hepatic encephalopathy for its ammonia lowering effect. A zinc-derivative of sodium benzoate (CH-1) with similar effects, is presented herein. We administered CH-1 at doses of 250, 500 and 1000 mg/kg body weight during 7 days to male Wistar rats after a portocaval shunt operation was performed as a model for experimental hyperammonemia. There was a decrease in blood ammonia levels in all groups receiving CH-1. A linear relationship (r=-0.487, P < 0.01) was observed between the dose of CH-1 and blood ammonia levels. The effective dose 50 (ED₅₀) was 320 mg/kg body weight (95% C.I. 176-581 mg) with a slope of 1.538 (Litchfield and Wilcoxon method). These results suggest that benzoic acid salts such as CH-1 may prove a new alternative for the treatment of hyperammonemia. Potential advantages of non-sodium salts of benzoic acid are discussed.