Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh 495009, India.
Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh 495009, India.
Life Sci. 2016 Dec 15;167:105-112. doi: 10.1016/j.lfs.2016.10.012. Epub 2016 Oct 13.
Previously we found that cadmium chloride (CdCl) exposure substantially elevates hypertension and potentiates cataract formation. In the present study, we investigated the protective effects of olmesartan, an angiotensin II receptor blocker against cataractogenesis in the CdCl-induced hypertensive animal model.
Male Sprague-Dawley albino rats (150-180g) were randomly selected and assigned to four groups (n=6). Among the four groups, one group (normal) received 0.3% carboxymethyl cellulose (10ml/kg/day, p.o.), another group (CdCl control) received CdCl (0.5mg/kg/day, i.p.), and remaining two groups received olmesartan at two doses level (2 and 4mg/kg/day, p.o.) concurrently with CdCl for six consecutive weeks. Blood pressure and cataract formation were examined biweekly, and pathophysiological parameters in serum and eye lenses were evaluated after six weeks of the experimental protocol.
The olmesartan treatment significantly restored the blood pressure, lenticular opacity, serum and lens antioxidants (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reduced), and malondialdehyde level. Additionally, it significantly restored the proteins, ions (Na, K, and Ca), and ATPase pumps activity (NaK ATPase and Ca ATPase) in the lens as compared to CdCl control group.
The findings demonstrate that olmesartan potentially inhibits the risk of cataract formation in the hypertensive state via restoration of lenticular oxidative stress, ATPase function, and ionic contents in the eye lenses. The results suggest that angiotensin II receptor blockers play an important role to prevent cataract formation in several pathogenic conditions like hypertension, diabetes, and oxidative stress.
此前我们发现氯化镉(CdCl)暴露会显著升高血压并增强白内障形成。在本研究中,我们研究了血管紧张素 II 受体阻滞剂奥美沙坦对 CdCl 诱导的高血压动物模型白内障形成的保护作用。
雄性 Sprague-Dawley 白化大鼠(150-180g)被随机选择并分为四组(n=6)。在这四组中,一组(正常)给予 0.3%羧甲基纤维素(10ml/kg/天,po),另一组(CdCl 对照组)给予 CdCl(0.5mg/kg/天,ip),其余两组同时给予奥美沙坦两种剂量水平(2 和 4mg/kg/天,po),连续六周。每两周检查一次血压和白内障形成情况,并在实验方案六周后评估血清和晶状体中的病理生理参数。
奥美沙坦治疗可显著恢复血压、晶状体混浊、血清和晶状体抗氧化剂(过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和还原型谷胱甘肽)以及丙二醛水平。此外,与 CdCl 对照组相比,它还显著恢复了晶状体中的蛋白质、离子(Na、K 和 Ca)和 ATP 酶泵活性(NaK ATP 酶和 Ca ATP 酶)。
这些发现表明,奥美沙坦通过恢复晶状体氧化应激、ATP 酶功能和眼内离子含量,可能抑制高血压状态下白内障形成的风险。结果表明,血管紧张素 II 受体阻滞剂在高血压、糖尿病和氧化应激等多种致病条件下预防白内障形成中发挥重要作用。