The effect of acetyl- l-carnitine on lenticular calpain activity in prevention of selenite-induced cataractogenesis

• Published in: Experimental eye research 2009-05, Vol.88 (5), p.938-944
• Main Authors: Elanchezhian, R., Sakthivel, M., Geraldine, P., Thomas, P.A.
• Format: Article
• Language: English
• Subjects: acetyl- l-carnitine; Acetylcarnitine - therapeutic use; Animals; Calcium - metabolism; Calpain - genetics; Calpain - metabolism; calpain activity; Cataract - chemically induced; Cataract - enzymology; Cataract - pathology; Cataract - prevention & control; cataractogenesis; Drug Evaluation, Preclinical - methods; Gene Expression Regulation, Enzymologic - drug effects; Lens, Crystalline - enzymology; Lens, Crystalline - metabolism; Lp82; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; selenite cataract; Sodium Selenite
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2008.12.009

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 (19 μmol/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 (200 mg/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.