El-Bassossy Hany M, Hassanien Mohammed A, Bima Abdulhadi, Ghoneim Fatma M, Elsamanoudy Ayman Zaky
Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
J Microsc Ultrastruct. 2019 Jan-Mar;7(1):44-49. doi: 10.4103/JMAU.JMAU_52_18.
The current study postulated that cyclosporine A (CSA) could induce gender-specific renal damage. Hence, the current study aims to investigate the nephrotoxic effect of perinatal exposure of male and female rat progeny to CSA. Moreover, it aims to evaluate the oxidative stress and inflammation as a possible pathophysiologic mechanism.
Female rats were randomly allocated to two groups of four and assigned to undergo either CSA (15 mg/kg/day; the 6 day after conception and continuing until the progeny were weaned) or vehicle treatment as control groups. At the age of 6 weeks, the progeny were divided into the following four groups: male progeny of control-group mothers (M-vehicle, 7); male progeny of CSA-treated mothers (M-CSA, 9); female progeny of control-group mothers (F-vehicle, 7); and female progeny of CSA-treated mothers (F-CSA, 6). Serum adiponectin, tumor necrosis factor-α (TNF-α) and creatinine, creatinine clearance, and urinary 8-isoprostane were measured. Histopathological examination by hematoxylin and eosin stain of Kidney was carried out.
Proteinuria and decreased creatinine clearance are significant in M-CSA than M-vehicle and F-CSA. 8-isoprostane is lower in F-CSA than F-vehicle. Increased TNF-α and decreased adiponectin levels in M-CSA than M-vehicle were observed. No significant differences were found in female rat groups.
From the current study, it could be concluded that CSA could induce renal inflammation as well as oxidative stress that may explain the impaired renal function. The sex difference was a prominent finding in their vulnerability to CSA effects.
当前研究推测环孢素A(CSA)可引发性别特异性肾损伤。因此,本研究旨在探究围产期雄性和雌性大鼠后代暴露于CSA后的肾毒性作用。此外,旨在评估氧化应激和炎症作为可能的病理生理机制。
将雌性大鼠随机分为两组,每组四只,分别接受CSA(15毫克/千克/天;受孕后第6天开始,持续至后代断奶)或作为对照组的载体处理。在6周龄时,后代分为以下四组:对照组母亲的雄性后代(M-载体组,7只);CSA处理组母亲的雄性后代(M-CSA组,9只);对照组母亲的雌性后代(F-载体组,7只);CSA处理组母亲的雌性后代(F-CSA组,6只)。检测血清脂联素、肿瘤坏死因子-α(TNF-α)和肌酐、肌酐清除率以及尿8-异前列腺素。对肾脏进行苏木精和伊红染色的组织病理学检查。
M-CSA组的蛋白尿和肌酐清除率降低比M-载体组和F-CSA组更显著。F-CSA组的8-异前列腺素低于F-载体组。观察到M-CSA组的TNF-α升高和脂联素水平降低比M-载体组更明显。雌性大鼠组未发现显著差异。
从当前研究可以得出结论,CSA可引发肾脏炎症以及氧化应激,这可能解释了肾功能受损的原因。性别差异是它们对CSA作用易感性的一个突出发现。