Farghaly Lamiaa M, Ghobashy Waleed A, Shoukry Youssef, El-Azab Mona F
Department of Histology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Eur J Pharmacol. 2014 Apr 15;729:1-9. doi: 10.1016/j.ejphar.2014.02.005. Epub 2014 Feb 14.
Free radical toxicity and calcium ion overload have been identified as the major two players in the causation of cataract. The current study was carried out to investigate the anti-cataractogenic effect of single and combined treatment with acetyl-l-carnitine and nifedipine in sodium selenite-induced cataract. Rat pups were divided into 5 groups; 1st group received intraperitoneal injection (i.p.) of saline and served as normal control, 2nd group received single subcutaneous injection of sodium selenite 30nmol/g body weight on p10 (postpartum day 10), 3rd and 4th groups received either acetyl-l-carnitine (200mg/kg, i.p.) or nifedipine (0.1mg/kg, i.p.) on p9, respectively, before the administration of sodium selenite, and the treatment continued till p14. Last group received the combined treatments of acetyl-l-carnitine and nifedipine in the same regimen. All animals were examined using a slit lamp and retroillumination then sacrificed on p30. Lenses were removed and processed for biochemical analyses, histopathological and electron microscopic examination. Selenite-treated groups showed significantly (P≤0.05) lower values of redox system components (glutathione and glutathione reductase activity) and anti-oxidant enzymes׳ activities (superoxide dismutase and catalase) along with increased lipid peroxidation that was accompanied by 100% opacified crystalline lenses (mature cataract) with abnormal structure as detected by electron microscopy. It is concluded that acetyl-l-carnitine or nifedipine was able to partially protect against selenite-induced abnormalities. While, combined treatment with acetyl-l-carnitine and nifedipine was superior to individual treatments in slowing down the development of cataract by restoring the anti-oxidant defense and mitigating lipid peroxidation in the lens and hence represents an attractive anti-cataractogenic remedy.
自由基毒性和钙离子超载已被确认为白内障形成的两大主要因素。本研究旨在探讨乙酰左旋肉碱和硝苯地平单独及联合治疗对亚硒酸钠诱导的白内障的抗白内障作用。将新生大鼠分为5组;第1组腹腔注射生理盐水作为正常对照,第2组在出生后第10天(p10)皮下注射30nmol/g体重的亚硒酸钠,第3组和第4组分别在p9于注射亚硒酸钠前腹腔注射乙酰左旋肉碱(200mg/kg)或硝苯地平(0.1mg/kg),治疗持续至p14。最后一组以相同方案接受乙酰左旋肉碱和硝苯地平的联合治疗。所有动物均用裂隙灯和后照法检查,然后在p30处死。取出晶状体进行生化分析、组织病理学和电子显微镜检查。亚硒酸钠处理组的氧化还原系统成分(谷胱甘肽和谷胱甘肽还原酶活性)和抗氧化酶活性(超氧化物歧化酶和过氧化氢酶)显著降低(P≤0.05),同时脂质过氧化增加,电子显微镜检测显示晶状体浑浊率达100%(成熟白内障)且结构异常。研究得出结论,乙酰左旋肉碱或硝苯地平能够部分预防亚硒酸钠诱导的异常。而乙酰左旋肉碱和硝苯地平联合治疗在减缓白内障发展方面优于单独治疗,其通过恢复晶状体的抗氧化防御和减轻脂质过氧化来实现,因此是一种有吸引力的抗白内障疗法。