Protective effect of the nitric oxide pathway in L-citrulline renal ischaemia-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.
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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Fu
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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S
Li
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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G
Jia
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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L
Gou
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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Tian
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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L
Sun
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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X
Ling
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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Lan
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
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Yin
School of Environment, Nanjing University, Nanjing, P. R. China.
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Ma
Xuzhou Environmental Monitoring Station, Xuzhou, P. R. China, Nanjing University, Nanjing, P. R. China.
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L
Liu
School of Pharmacy, Xuzhou Medical College, Nanjing University, Nanjing, P. R. China.
Y
Y
Liu
D000818:Animals; D002956:Citrulline / Q000494:pharmacology* / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D002956:Citrulline; D009569:Nitric Oxide