The effect of acetyl-L-carnitine on lenticular calpain activity in prevention of selenite-induced cataractogenesis.
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.
Elanchezhian
R
R
Department of Animal Science, School of Life Sciences, Bharathidasan University, Tamil Nadu, India.
Sakthivel
M
M
Geraldine
P
P
Thomas
P A
PA
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002386:Cataract / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007908:Lens, Crystalline / Q000201:enzymology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018038:Sodium Selenite
D012333:RNA, Messenger; D000108:Acetylcarnitine; D002154:Calpain; C118624:calpain Lp82; D018038:Sodium Selenite; D002118:Calcium