一种特异性诱导型一氧化氮合酶抑制剂——半硫酸S-甲基异硫脲对顺铂诱导的肾毒性的影响；性别相关差异。
The effect of an specific inducible NO synthase inhibitor, S-methylisothiourea hemisulfate on cisplatin-induced nephrotoxicity; gender-related differences.
作者信息
Ghayyoomi Mansooreh, Soltani Nepton, Nematbakhsh Mehdi, Moslemi Fatemeh, Talebi Ardeshir, Shirdavani Soheila, Razmjoo Farzaneh
机构信息
Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran.
出版信息
Adv Biomed Res. 2015 Jul 20;4:130. doi: 10.4103/2277-9175.161223. eCollection 2015.
BACKGROUNDS
It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.
MATERIALS AND METHODS
Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.
RESULTS
Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.
CONCLUSION
It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.
背景
先前已有研究表明，一氧化氮（NO）水平升高可能会促进顺铂（CP）诱导的肾毒性。本研究旨在探讨诱导型一氧化氮合酶（iNOS）抑制剂在预防CP诱导的肾毒性中的作用。
材料与方法
将四组雄性和四组雌性大鼠每日分别用赋形剂、作为选择性iNOS抑制剂的半硫酸S-甲基异硫脲（SMT，5 mg/kg/每日两次）、CP（2.5 mg/kg/天）以及CP + SMT处理6天。然后，处死所有动物并测定血清肌酐（Cr）、血尿素氮（BUN）、亚硝酸盐和丙二醛（MDA）水平。立即取出肾脏进行组织病理学研究。
结果
我们的结果表明，SMT对iNOS的抑制在雄性和雌性动物中产生了不同的反应。雄性动物接受SMT治疗后，血清BUN、Cr、亚硝酸盐和MDA水平降低；并且它还保护肾脏免受CP诱导的肾毒性。
结论
得出的结论是，SMT减少NO生成对减轻雄性CP诱导的肾毒性具有有益作用。然而，在雌性动物中未观察到这种有益作用。
Zotero 插件