Effect of hydrazine upon vitamin B-12-dependent methionine synthase activity and the sulphur amino acid pathway in isolated rat hepatocytes

The effect of the industrial chemical, hydrazine (4-12 mM), on methionine s ynthase (EC 2.1.1.13) activity and levels of the sulphur amino acids homocy steine, cysteine, and taurine as well as GSH were investigated in vitro in isolated rat hepatocyte suspensions and monolayers in order to explain some of the adverse in vivo effects of hydrazine. None of the concentrations of hydrazine were overtly cytotoxic in hepatocyte suspensions (measured as la ctate dehydrogenase [LDH] leakage) after 3 hr. However, after 24 hr in cult ure cells treated with 12 mM, hydrazine showed a significant increase in LD H leakage. Methionine synthase activity was reduced by hydrazine (8 and 12 mM) in suspensions (by 45 and 55%, after 3 hr) and monolayers (12 mM; 65-80 % after 24 hr). This was not due to nitric oxide production and the inhibit or of nitric oxide synthase, N-omega-nitro-L-arginine, failed to protect ag ainst the hydrazine-induced loss of ATP and GSH and the reduction in urea s ynthesis at 24 hr. Homocysteine export was increased by 6 mM hydrazine, and total taurine content of treated cells was increased by 12 mM hydrazine. T hus, hydrazine was found to have several important and possibly deleterious effects on some parts of the sulphur amino acid pathway. BIOCHEM PHARMACOL 57;11: 1311-1319, 1999. (C) 1999 Elsevier Science Inc.