Beneficial Effect of Arginase A1 on Murine Septic Shock

Background and purpose: L-arginine is a substrate for arginase, and is also a source of nitric oxide that mediates hypotension in septic shock. The possibility of arginase protection against septic shock was studied. Methods: For experiments of single-dose intravenous injection with arginase A1 (5 μg/mouse), various doses of Escherichia coli (E. coli) were simultaneously injected into the intraperitoneum of each BALB/c mouse. The survival rates were observed for three days. For experiments with multiple-dose injections of arginase, mice were intravenous injected with arginase A1 (5 μg/day/mouse) daily from day 1 to day 4, and E. coli was introduced on day 3. Results: For experiments with multiple doses of arginase A1, when each mouse was injected with E. coli at a dose of 1.6 × 107 colony forming units, they were significantly protected from death by the effect of arginase (P = 0.008). This protection was arginase-dose related and was not a result of direct inhibition by arginase on bacterial growth, or by the presence of L-arginine-degradation products, L-ornithine and urea. Single injection of arginase did not confer a significant protection. Conclusion: Multiple injections of arginase A1 do protect E. coli-induced mice to some extent from death of septic shock, while single injection of arginase did not.