Dipeptiven® is safe in a rat model of moderate liver dysfunction

Abstract

Summary: Background & aims: Administration of glutamine in patients with liver failure is thought to possibly increase blood ammonia levels, thereby contributing to hepatic encephalopathy. In a rat model of moderate liver dysfunction with elevated plasma glutamine concentrations dose-dependent effects of intravenous alanyl-glutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods: Rats with moderate liver dysfunction resulting from alpha-naphthylisothiocyanate (ANIT) induced cholestasis received a 9 days continuous intravenous infusion of 0.5 g/kg/day or 3.0 g/kg/day alanyl-glutamine (Dipeptiven®). Dose-dependent effects on liver injury were assessed by analyzing blood levels of ammonia, urea, ALT, AST, and ALP, glutamine, and histopathology. Results: Continuous intravenous infusion of 3.0 g/kg/day alanyl-glutamine increased plasma glutamine concentrations up to 30% without increasing blood ammonia levels or inducing astrocyte swelling. Alanyl-glutamine did not aggravate underlying liver injury shown by absent increase in plasma levels of ALT, AST, ALP and no signs of histopathologic alterations. Conclusions: Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat model of moderate liver dysfunction based on ANIT-induced cholestasis. Keywords: Ammonia, Astrocyte swelling, Brain edema, Cholestasis, Glutamine, Liver injury