Glycine Pretreatment Ameliorates Liver Injury After Partial Hepatectomy in the Rat

ABSTRACT

Background: Living donor liver transplantation subjects the donor to a major hepatectomy. Pharmacological or nutritive protection of the liver during the procedure is desirable to ensure that the remnant is able to maintain sufficient function. The aim of our study was to analyze the effects of pretreatments with α-tocopherol (vitamin E), the flavonoid silibinin and/or the amino acid L-glycine on the donor in a rat model. Methods: Male Wistar rats were pretreated with L-glycine (5%% in chow, 5 days), α-tocopherol (100 mg/kg body weight by gavage, 3 days) and/or silibinin (100 mg/kg body weight, i.p., 5 days). Thereafter, 90%% partial hepatectomy was performed without portal vein clamping. Results: Glycine pretreatment markedly decreased transaminase release (AST, 12 hr: glycine 1292 ± 192 U/L, control 2311 ± 556 U/L, p < .05; ALT, 12 hr: glycine 1013 ± 278 U/L, control 2038 ± 500 U/L, p < .05), serum ALP activity and serum bilirubin levels (p < .05). Prothrombin time was reduced, and histologically, liver injury was also decreased in the glycine group. Silibinin pretreatment was less advantageous and pretreatment with α-tocopherol at this very high dose showed some adverse effects. Combined, i.e., triple pretreatment was less advantageous than glycine alone. Liver resection induced HIF-1α accumulation and HIF-1α accumulation was also decreased by glycine pretreatment. Conclusion: The decrease of liver injury and improvement of liver function after pretreatment with glycine suggests that glycine pretreatment might be beneficial for living liver donors as well as for patients subjected to partial hepatectomy for other reasons.

• KEYWORDS

Keywords: :

• glycine
• liver resection
• living donor liver transplantation
• α-tocopherol
• silibinin
• HIF-1α

ACKNOWLEDGEMENT

The authors would like to thank Ms. N. Boschenkov, Ms. B. Podleska, Ms. P. Freitag, and Ms. D. Möllmann for their excellent technical assistance.

This study was supported by the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe “Optimierung der Leberlebendspende,” KFO 117). Tamas Benko received a grant from the Deutscher Akademischer Austauschdienst (DAAD).