Fol. Biol. 2013, 59, 225-232
Protective Effect of the Nitric Oxide Pathway in L-Citrulline Renal Ichaemia-Reperfusion Injury in Rats
To observe the protective effects of L-citrulline on the renal I/R injury and elucidate the mechanisms involved, 48 rats were randomized into eight groups: Group 1: sham operated; Group 2: I/R (45 min renal ischaemia and 24 h reperfusion); Group 3: I/R + L-citrulline (300 mg/kg, i.g.); Group 4: I/R + L-citrulline (600 mg/kg, i.g.); Group 5: I/R + L-citrulline (900 mg/kg, i.g.); Group 6: I/R + normal saline (NS, i.g.); Group 7: I/R + N sup ω nitro-L-arginine ester (L-NAME, 20 mg/kg, i.p.); Group 8: I/R + L-citrulline (900 mg/kg, i.g.) + L-NAME (20 mg/ kg, i.p.). At the end of the reperfusion period, serum was collected and the kidneys underwent histological and biochemical examinations. Our results showed that pre-treatment with L-citrulline (300, 600, and 900 mg/kg) significantly ameliorated the renal injury caused by I/R. Moreover, L-citrulline prevented induction of lipid peroxidation and increased the activity of superoxide dismutase and the levels of glutathione and nitric oxide. The I/R-induced decreases in total nitric oxide synthase activity, inducible nitric oxide activity, constitutive nitric oxide activity and endothelial nitric oxide protein expression in the renal cortex were significantly prevented. However, the L-citrulline-mediated protection was significantly antagonized by co-administration of L-NAME. These results suggested that L-citrulline administration exhibited significant protection against renal I/R injury. This protective effect, at least in part, via up-regulation of the endothelial nitric oxide protein expression and constitutive nitric oxide synthase activity, maintained production of nitric oxide at the basal level.
Keywords
L-citrulline, ischaemia-reperfusion, nitric oxide synthase, L-NAME.
Funding
The project was financially supported by “Qing-Lan” Project of Jiangsu Province, the Industrialization of Scientific Research Promotion Projects of Universities and Colleges in Jiangsu Province (2011-16), the Science and Technology Plan Projects of Xuzhou (XF11C037; XF11C062; XF11C065; X22D1219), Superiority Academic Discipline Construction Project of Jiangsu Higher Education Institutions, Open research project of Jiangsu Key Laboratory of Bioinformation of Brain Diseases (Jsbl1103, Jsbl1104), “Six-Major-Talent-Summit” Project of Jiangsu Province, The research project of Xuzhou (BRA201205). Xiaobin Fu and Sai Li are both co-first authors of this paper.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
