Aliskiren – a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS

Abstract

The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1β, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system.

Chinese abstract

本研究的目的是评估阿利吉仑, 一种直接肾素抑制剂, 作为抗氧化剂和组织保护剂, 在大鼠卵巢实验性缺血和缺血/再灌注损伤中的分子, 生物化学和组织病理学变化。48只雌性大鼠随机分为8组: 组1的大鼠接受假手术, 组2接受假手术及100 mg/kg的阿利吉仑治疗, 对第3组大鼠实施长达3小时的双侧卵巢缺血, 组4在3小时的双侧卵巢缺血后进行3小时再灌注。组5和组6分别接受50 mg/kg和100 mg/kg的阿利吉仑治疗, 并实施双侧卵巢缺血（在3小时卵巢缺血后手术切除双侧卵巢）。在组7和组8中, 分别给予50 mg/kg和100 mg/kg的阿利吉仑治疗, 并诱导缺血形成, 在3小时卵巢缺血后, 取出双侧血管夹, 进行3小时的再灌注。试验完成后, 测定IL-1β, IL-6, TNF-a和iNOS的mRNA表达以及超氧化物歧化酶, 谷胱甘肽, 丙二醛, 肾素和血管紧张素II的水平, 对大鼠卵巢进行组织病理学检查并观察其变化。阿利吉仑治疗使缺血及缺血-再灌注损伤导致的细胞因子及氧化应激的升高变化正常化。组织病理学方面, 阿利吉仑使缺血及缺血-再灌注损伤造成的变化大大减轻。本研究可得出结论: 阿利吉仑可降低氧化应激反应及炎症反应, 并通过抑制肾素-血管紧张素-醛固酮系统有效地改善并逆转缺血和缺血-再灌注诱导的卵巢损伤。

• Aliskiren
• ischemia
• ovary
• oxidative stress
• rat
• reperfusion

Declaration of interest

The authors report that they have no conflicts of interest. This study was supported by the Research fund of Atatürk University (BAP-2012/394) and was conducted in the of Pharmacology, Biochemistry and Histology Laboratories of Faculty of Medicine and Biochemistry Laboratory of Faculty of Pharmacy at Ataturk University, 25240 Erzurum/Turkey. None of the authors has any commercial and/or financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.