Glycine pretreatment ameliorates liver injury after partial hepatectomy in the rat.
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 alpha-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), alpha-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 alpha-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-1alpha accumulation and HIF-1alpha accumulation was also decreased by glycine pretreatment.


CONCLUSIONS
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.
Department of Surgery and Transplantation, Semmelweis University, Budapest, Hungary.
Tamas
T
Benko
Stilla
S
Frede
Yanli
Y
Gu
Jan
J
Best
Hideo Andreas
HA
Baba
Jörg Friedrich
JF
Schlaak
Herbert
H
de Groot
Joachim
J
Fandrey
Ursula
U
Rauen
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005998:Glycine / Q000008:administration & dosage / Q000627:therapeutic use*; D006498:Hepatectomy / Q000379:methods*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control*; D016031:Liver Transplantation; D008297:Male; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D011229:Preanesthetic Medication; D011517:Prothrombin Time; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use; D020858:Tissue and Organ Harvesting / Q000379:methods; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000627:therapeutic use
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012838:Silymarin; D000077385:Silybin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D024502:alpha-Tocopherol; D005998:Glycine