Elanchezhian R, Sakthivel M, Geraldine P, Thomas P A
Department of Animal Science, School of Life Sciences, Bharathidasan University, Tamil Nadu, India.
Exp Eye Res. 2009 May;88(5):938-44. doi: 10.1016/j.exer.2008.12.009. Epub 2008 Dec 30.
The present study sought to determine whether acetyl-L-carnitine (ALCAR) prevents selenite cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19micromol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl-L-carnitine (200mg/kg body weight) on postpartum days 9-14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca(2+) concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.
本研究旨在确定乙酰左旋肉碱（ALCAR）是否通过涉及晶状体钙蛋白酶活性的机制来预防亚硒酸盐诱导的白内障形成。将Wistar大鼠幼崽分为3组，每组15只。第I组（正常）大鼠在出生后第10天腹腔注射生理盐水；第II组（未治疗白内障）大鼠在出生后第10天皮下注射一次亚硒酸钠（19微摩尔/千克体重）；第III组（治疗白内障）幼崽在出生后第10天皮下注射一次亚硒酸钠，并在出生后第9 - 14天腹腔注射乙酰左旋肉碱（200毫克/千克体重）。在研究期结束时（出生后第16天），通过裂隙灯生物显微镜检查每只大鼠幼崽的双眼。第II组所有大鼠晶状体均出现致密混浊，第III组33%的大鼠晶状体混浊轻微，第III组67%的大鼠和第I组所有大鼠晶状体均无混浊。第II组晶状体的钙蛋白酶活性和Lp82（晶状体特异性钙蛋白酶）蛋白表达的平均值显著降低，m - 钙蛋白酶mRNA的相对转录水平下降，且平均Ca(2+)浓度显著高于第I组或第III组晶状体；第III组大鼠晶状体（经ALCAR治疗）的这些参数值接近第I组大鼠晶状体。结果表明，除了其已描述的抗氧化潜力外，ALCAR通过将钙蛋白酶活性维持在接近正常水平来预防亚硒酸盐诱导的白内障形成。这些发现可能会促使人们进一步努力将ALCAR开发为一种预防白内障的新型药物。
