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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.

It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain α-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain α-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.

A dextran-bonded nitroxide radical (TEMPO-DX) was synthesized to obtain a radical with long life in vivo for ESR imaging. TEMPO-DX was injected intravenously into a rat tail vein and the decrease in ESR intensity in the collected, circulating blood was followed. The result showed that the half life of TEMPO-DX in vivo was 30 min, the longest value reported so far and more than 30 times longer than the corresponding radicals of the six-membered piperidine ring, which means that the bonding of a radical to the polymer greatly prolonged life. The stabilities of TEMPO-DX against the reduction with L-ascorbic acid and the rat liver homogenate were also examined and compared with those of the 3-carbamoyl-2,2,5,5-tetramethylpyrolidin-1-yloxy (CPROXYL) known as a radical stable in vivo. TEMPO-DX was shown not to be as stable as CPROXYL, thus in vivo stability of TEMPO-DX arises from the fact that it is slowly absorbed into the tissues where the radicals are quenched. An ESR image of the mouse head domain was obtained only by an intravenous injection of TEMPO-DX solution into the tail vein.