Yang Ying, Wu Zhenlong, Jia Sichao, Dahanayaka Sudath, Feng Shuo, Meininger Cynthia J, McNeal Catherine J, Wu Guoyao
Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA.
Amino Acids. 2015 Sep;47(9):1909-20. doi: 10.1007/s00726-015-1992-3. Epub 2015 May 7.
This study was conducted with rats to determine the safety of long-term dietary supplementation with L-arginine. Beginning at 6 weeks of age, male and female rats were fed a casein-based semi-purified diet containing 0.61 % L-arginine and received drinking water containing L-arginine-HCl (0, 1.8, or 3.6 g L-arginine/kg body-weight/day; n = 10/group). These supplemental doses of L-arginine were equivalent to 0, 286, and 573 mg L-arginine/kg body-weight/day, respectively, in humans. After a 13-week supplementation period, blood samples were obtained from rats for biochemical analyses. Supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, homoarginine, urea, and nitric oxide metabolites without affecting those for lysine, histidine, or methylarginines, while reducing plasma concentrations of ammonia, glutamine, free fatty acids, and triglycerides. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Based on general appearance, feeding behavior, and physiological parameters, all animals showed good health during the entire experimental period; Plasma concentrations of all measured hormones (except leptin) did not differ between control and arginine-supplemented rats. L-Arginine supplementation reduced plasma levels of leptin. Additionally, L-arginine supplementation increased L-arginine:glycine amidinotransferase activity in kidneys but not in the liver or small intestine, suggesting tissue-specific regulation of enzyme expression by L-arginine. Collectively, these results indicate that dietary supplementation with L-arginine (e.g., 3.6 g/kg body-weight/day) is safe in rats for at least 91 days. This dose is equivalent to 40 g L-arginine/kg body-weight/day for a 70-kg person. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.
本研究以大鼠为对象，旨在确定长期膳食补充L-精氨酸的安全性。从6周龄开始，雄性和雌性大鼠喂食含0.61% L-精氨酸的酪蛋白基半纯化日粮，并饮用含L-精氨酸盐酸盐的水（0、1.8或3.6 g L-精氨酸/千克体重/天；每组n = 10）。这些L-精氨酸补充剂量在人类中分别相当于0、286和573 mg L-精氨酸/千克体重/天。经过13周的补充期后，采集大鼠血样进行生化分析。补充L-精氨酸可提高血浆中精氨酸、鸟氨酸、脯氨酸、高精氨酸、尿素和一氧化氮代谢物的浓度，而不影响赖氨酸、组氨酸或甲基精氨酸的浓度，同时降低血浆中氨、谷氨酰胺、游离脂肪酸和甘油三酯的浓度。补充L-精氨酸可促进蛋白质增加并减少体内白色脂肪沉积。基于总体外观、摄食行为和生理参数，所有动物在整个实验期间均表现健康；对照大鼠和补充精氨酸的大鼠之间，所有测量激素（除瘦素外）的血浆浓度均无差异。补充L-精氨酸可降低血浆瘦素水平。此外，补充L-精氨酸可增加肾脏中L-精氨酸：甘氨酸脒基转移酶的活性，但在肝脏或小肠中未增加，提示L-精氨酸对酶表达的组织特异性调节。总体而言，这些结果表明，膳食补充L-精氨酸（如3.6 g/千克体重/天）在大鼠中至少91天是安全的。该剂量相当于70千克体重的人每天4Og L-精氨酸/千克体重。我们的研究结果有助于指导临床研究，以确定长期口服L-精氨酸对人类的安全性。
