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

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Dipeptiven® is safe in a rat model of moderate liver dysfunction Melanie K. Bothe, Rosa Abele, Heinrich Topp, Johannes Harleman, Martin Westphal, John F. Stover Clinical Nutrition Experimental Volume 21, Pages 9-17 (October 2018) DOI: 10.1016/j.yclnex.2018.07.001 Copyright © 2018 The Authors Terms and Conditions

Fig. 1 After one week of daily ANIT or vehicle administration via oral gavage the rats additionally received a continuous intravenous infusion or either Ala-Gln (Dipeptiven®) or saline. Ala-Gln = alanyl-glutamine, ANIT = alpha-naphthylisothiocyanate. Clinical Nutrition Experimental 2018 21, 9-17DOI: (10.1016/j.yclnex.2018.07.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 2 Plasma glutamine concentrations in (A) ANIT-induced cholestatic rats compared to vehicle receiving sham control and (B) ANIT-induced cholestatic rats undergoing either Ala-Gln or saline infusion. ANIT-induced cholestasis significantly increased plasma glutamine concentrations by 30%. Ala-Gln infusion of 3.0 g/kg/day, but not 0.5 g/kg/day, Ala-Gln consistently further increased the plasma glutamine concentrations on infusion days 2 and 9. Statistical significance was reached on day 9. The plasma glutamine levels of the vehicle receiving rats in (A) are represented by the grey shaded horizontal bar in (B). Ala-Gln = alanyl-glutamine, ANIT = alpha-naphthylisothiocyanate, * = p < 0.05, ** = p < 0.01, data reported as mean and interquartile range (IQR). Clinical Nutrition Experimental 2018 21, 9-17DOI: (10.1016/j.yclnex.2018.07.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 3 Blood ammonia (A) and plasma urea (B) levels are not increased in the ANIT-induced cholestatic rats compared to sham control (grey shaded horizontal bar). Ala-Gln infusion did not increase ammonia levels and rather reduced plasma urea levels. * = p < 0.05, data in Fig. 3b reported as mean and IQR. Clinical Nutrition Experimental 2018 21, 9-17DOI: (10.1016/j.yclnex.2018.07.001) Copyright © 2018 The Authors Terms and Conditions

Fig. 4 Mean plasma ALT (A) and ALP (B) levels are increased in all ANIT-induced cholestatic rats (control and Ala-Gln treated) compared to sham animals (grey shaded horizontal bar) on day 2 (ANIT administration day 9), while mean AST (C) levels are in the reference range. Ala-Gln infusion did not statistically significantly increase the plasma ALT, ALP, and AST levels further. Data reported as mean and IQR, Ala-Gln = alanyl-glutamine, ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, ANIT = alpha-naphthylisothiocyanate. Clinical Nutrition Experimental 2018 21, 9-17DOI: (10.1016/j.yclnex.2018.07.001) Copyright © 2018 The Authors Terms and Conditions