Histidinemia produced in the rat by treatment with nitromethane1

Metabolic effects of in vivo administration of nitromethane, a histidase inhibitor, were studied in the rat. Histidinemia produced by feeding a 5-percent histidine diet to the rat was included for comparison. Rats injected subcutaneously with nitromethane every other day appeared to be histidinemic, with a plasma histidine level of 43 mumol/100 ml (control 9.2 mumol/100 ml) after 12 days of treatment. Histidine concentrations in the brain, liver, kidney, and urine of the nitromethane-treated rats were also increased. Liver histidase activity was decreased about 78 percent after nitromethane administration, and the rate of in vivo CO2 production from histidine was also depressed. No abnormal change in liver and kidney sizes was observed in these animals. Rats fed the 5-percent histidine diet showed markedly higher plasma histidine concentrations (99 mumul/100 ml) than the nitromethane-treated rats. The magnitude of increase in plasma histidine in the histidine-fed rats was considerably greater than that observed in humans with histidinemia. Furthermore, the liver histidase activity was decreased only by about 20 percent, and a significant increase in liver and kidney sizes was noted in the histidine-fed animals. These findings indicate that histidinemia produced by nitromethane administration is a better model for studies of the genetic disorder than histidinemia induced by high levels of histidine in the diet.