On the significance of nitric monoxide, arginase activity and liver detoxication function in the mechanism of urea’s antipyretic action in endotoxic fever

The importance of urea in vital processes in health and disease is well known. Specifically, we have found that increasing blood urea levels prevents the development of a febrile reaction. However, the mechanism of urea’s antipyretic effect has not been elucidated.

The aim of the study was to determine the significance of nitric oxide, arginase activity and liver detoxication function in the mechanism of the antipyretic effect of urea under endotoxin fever conditions.

Experiments on rats and rabbits have shown that the urea blood level, by influencing the arginase, L-arginine-NO system activity and liver detoxication processes, is important for the formation of body temperature in rats when exposed to bacterial endotoxin. The action of bacterial endotoxin in the body, along with an increase in body temperature, leads to an increase in arginase activity and the liver detoxication function, the level of urea, NO3–/NO2– and a decrease in the level of arginine concentration in the blood plasma of animals. Intraperitoneal administration of urea to rats or into the bloodstream of rabbits at a dose of 3.0 g/kg has an antipyretic effect and leads to a decrease in liver arginase activity, detoxication function arginine content and an increase in the level of NO3–/NO2– in the blood plasma.

The study results suggest that arginase activity and liver detoxication function, as well as the interaction of the L-arginine-NO system with the urea cycle, play a key role in the mechanism of endogenous antipyresis, determining urea and NO levels in the blood and tissues. Increased activity of the L-arginine-NO system and the leakage of L-arginine from the urea cycle into the NO cycle are crucial for the antipyretic action of urea under endotoxin-induced fever.

The obtained data are important for understanding the significance of arginase activity, liver L-arginine-NO system, and urea blood level in the mechanisms of maintaining temperature homeostasis, and also contribute to the development of ideas about the pathogenesis of febrile conditions and the mechanisms of endogenous antipyresis.

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