Abstract

BackgroundNitric oxide (NO) has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. NO is the oxidative metabolite of L-arginine, and is produced by a family of enzymes, collective termed nitric oxide synthase (NOS). Thus, administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Thus, the present study was undertaken to evaluate the effects of an L-arginine supplement on liver regeneration, and to compared this with supplementation with L-glutamine and L-alanine (the latter as a negative control), using a rat partial hepatectomy model.MethodsBefore and after a 70% hepatectomy, rats received one of three amino acid solutions (L-arginine, L-glutamine, or L-alanine). The effects on liver regeneration of the administered solutions were examined by assessment of restituted liver mass, staining for proliferating cell nuclear antigen (PCNA), and total RNA and DNA content 24 and 72 hours after the operation.ResultsAt 72 hours after the hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA quantity were all significantly higher in the L-arginine and L-glutamine groups than in the control. There were no significant differences in those parameters between the L-arginine and L-glutamine groups, nor were any significant differences found between the L-alanine group and the control.ConclusionOral supplements of L-arginine and L-glutamine enhanced liver regeneration after hepatectomy in rats, suggesting that an oral arginine supplement can clinically improve recovery after a major liver resection.

Highlights

  • Nitric oxide (NO) has been reported to be a key mediator in hepatocyte proliferation during liver regeneration

  • NO is enzymatically synthesized from L-arginine (L-Arg) by three nitric oxide synthase (NOS) isoforms: neuronal (n)NOS, inducible (i)NOS and endothelial (e) NOS. Endothelial nitric oxide synthase (eNOS) is a crucial mediator of vascular tone and blood flow, and plays major roles in liver physiology and pathophysiology [4]

  • Restituted liver mass No significant differences in liver mass were evident in any group at 24 hours after partial hepatectomy

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Summary

Introduction

Nitric oxide (NO) has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. Administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Nitric oxide (NO) is known to be a multifunctional mediator, regulating blood pressure, gene expression, apoptosis, and mitogenesis in essentially every organ and tissue [1,2,3]. ENOS is a crucial mediator of vascular tone and blood flow, and plays major roles in liver physiology and pathophysiology [4]. NO has been reported to reduce organ injury and enhance liver regeneration by experimentally modulating hepatic macrohaemodynamics [5]

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