Sattarinezhad Elahe, Panjehshahin Mohammad Reza, Torabinezhad Simin, Kamali-Sarvestani Eskandar, Farjadian Shirin, Pirsalami Fatema, Moezi Leila
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Nephrology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Med Sci. 2017 Mar;42(2):170-178.
Cyclosporine A (CsA) is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property.
Male Sprague-Dawley rats (n=66) were distributed into nine groups, including a control (group 1) (n=7). Eight groups received CsA (15 mg/kg) for 28 days while being treated. The groups were categorized as: Group 2: Vehicle (n=10)Groups 3, 4, and 5: Edaravone (1, 5, and 10 mg/kg) (n=7 each)Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase (eNOS) inhibitor (n=7)Group 7: Aminoguanidine, a specific inducible nitric oxide synthase (iNOS) inhibitor (n=7)Group 8: Edaravone (10 mg/kg) plus diphenyliodonium chloride (n=7)Group 9: Edaravone (10 mg/kg) plus aminoguanidine (n=7) Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's test (SPSS software version 18.0).
Edaravone (10 mg/kg) significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly.
Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression.
环孢素A（CsA）是一种免疫抑制剂，在多种免疫性疾病中具有治疗指征；然而，其使用与慢性肾病相关。氧化应激在CsA诱导的肾毒性中起关键作用。本研究评估依达拉奉对CsA诱导的慢性肾病的保护作用，并研究其抗氧化和一氧化氮调节特性。
将雄性Sprague-Dawley大鼠（n = 66）分为九组，包括对照组（第1组）（n = 7）。八组大鼠在接受治疗的同时给予CsA（15 mg/kg），持续28天。分组如下：第2组：赋形剂组（n = 10）；第3、4和5组：依达拉奉（1、5和10 mg/kg）组（每组n = 7）；第6组：二苯基碘鎓氯化物，一种特异性内皮型一氧化氮合酶（eNOS）抑制剂（n = 7）；第7组：氨基胍，一种特异性诱导型一氧化氮合酶（iNOS）抑制剂（n = 7）；第8组：依达拉奉（10 mg/kg）加二苯基碘鎓氯化物（n = 7）；第9组：依达拉奉（10 mg/kg）加氨基胍（n = 7）。使用标准试剂盒测量血尿素氮和血清肌酐水平、丙二醛、超氧化物歧化酶和谷胱甘肽还原酶活性。还进行了肾脏组织病理学评估以及通过逆转录聚合酶链反应（RT-PCR）测量eNOS和iNOS基因表达。数据采用单因素方差分析（ANOVA），随后进行Tukey检验（SPSS软件18.0版）进行分析。
依达拉奉（10 mg/kg）显著减轻了CsA诱导的氧化应激、肾功能障碍和肾组织损伤。氨基胍增强了依达拉奉的肾脏保护作用。依达拉奉降低了iNOS升高的mRNA水平，但未显著改变eNOS mRNA水平。
依达拉奉通过其抗氧化特性并可能通过抑制iNOS基因表达来预防CsA诱导的慢性肾病。
