Gupta Suresh K, Srivastava Sushma, Trivedi Deepa, Joshi Sujata, Halder Nabanita
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Curr Eye Res. 2005 Jul;30(7):583-91. doi: 10.1080/02713680590968132.
To study the effect of Ocimum sanctum (OS) on selenite-induced morphological and biochemical changes in isolated rat lenses as well as on cataract incidence in rat pups.
Transparent rat lenses were divided into normal, selenite-only, and four treated groups. Selenite-only and treated group lenses were subjected to oxidative stress in vitro by incorporating sodium selenite (100 microM) in the culture medium. The effect of OS (70, 140, 280, and 560 microg/ml) was studied on the levels of reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS) in selenite-challenged lenses. The lowest concentration of OS offering significant modulation on these two parameters was determined. Subsequently, the effect of prior and cotreatment with the lowest effective concentration of OS was studied on TBARS, GSH, and on lens antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), and glutathione-S-transferase (GST). Changes in lens protein profiles under different incubation conditions were analyzed by SDS gel-electrophoresis. In vivo, cataract was induced by a single subcutaneous injection of sodium selenite (25 micromole/kg b.w.) to 9-day-old rat pups. The anticataract effect of OS (5 and 10 mg/kg b.w.) injected intraperitoneally 4 hr prior to selenite challenge was evaluated by the presence of lens nuclear opacity in rat pups on the 16th postnatal day. Insolubilization of lens proteins post-selenite injection was monitored for 4 days.
The lenses in the selenite-only group developed cortical opacities in 24 hr. OS showed different degrees of positive modulation in selenite-induced morphological as well as biochemical changes. The lowest effective dose of OS that significantly modulated glutathione and thiobarbituric acid reacting substances was found to be 140 microg/ml. At this dose, a significant increase in antioxidant enzyme levels and preservation of normal lens protein profile was observed. OS at the dose of 70 microg/ml did not show any significant protection with respect to either morphology or biochemistry of lenses. In vivo, 5 and 10 mg/kg of OS reduced the incidence of selenite cataract by 20% and 60%, respectively, and prevented protein insolubilization as well.
Aqueous extract of OS possesses potential anticataract activity against selenite-induced experimental cataractogenesis. The protective effect was supported by restoration of the antioxidant defense system and inhibition of protein insolubilization of rat lenses as well.
研究神圣罗勒(OS)对亚硒酸盐诱导的离体大鼠晶状体形态和生化变化以及对幼鼠白内障发病率的影响。
将透明的大鼠晶状体分为正常组、仅用亚硒酸盐组和四个处理组。仅用亚硒酸盐组和处理组的晶状体通过在培养基中加入亚硒酸钠(100微摩尔)在体外遭受氧化应激。研究了OS(70、140、280和560微克/毫升)对亚硒酸盐攻击的晶状体中还原型谷胱甘肽(GSH)和硫代巴比妥酸反应物质(TBARS)水平的影响。确定了对这两个参数具有显著调节作用的OS的最低浓度。随后,研究了用最低有效浓度的OS预先处理和同时处理对TBARS、GSH以及晶状体抗氧化酶如超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)和谷胱甘肽-S-转移酶(GST)的影响。通过SDS凝胶电泳分析不同孵育条件下晶状体蛋白质谱的变化。在体内,通过对9日龄幼鼠单次皮下注射亚硒酸钠(25微摩尔/千克体重)诱导白内障。在亚硒酸盐攻击前4小时腹腔注射OS(5和10毫克/千克体重)的抗白内障作用通过出生后第16天幼鼠晶状体核混浊的情况进行评估。监测亚硒酸盐注射后晶状体蛋白质的不溶性4天。
仅用亚硒酸盐组的晶状体在24小时内出现皮质混浊。OS在亚硒酸盐诱导的形态和生化变化中表现出不同程度的正向调节作用。发现对谷胱甘肽和硫代巴比妥酸反应物质具有显著调节作用的OS的最低有效剂量为140微克/毫升。在此剂量下,观察到抗氧化酶水平显著增加以及正常晶状体蛋白质谱得以保留。70微克/毫升剂量的OS在晶状体的形态或生化方面均未显示出任何显著的保护作用。在体内,5和10毫克/千克体重的OS分别使亚硒酸盐白内障的发病率降低了20%和60%,并且也防止了蛋白质的不溶性。
OS水提取物对亚硒酸盐诱导的实验性白内障形成具有潜在的抗白内障活性。抗氧化防御系统的恢复以及对大鼠晶状体蛋白质不溶性的抑制也支持了这种保护作用。