Inhibition of lens crystallin glycation and high molecular weight aggregate formation by aspirin in vitro and in vivo.
Previous studies have shown that glycation of lens proteins could be a contributory factor in the development of diabetic and senile cataracts. Acetylation by aspirin (acetylsalicylic acid or ASA) has been used as an inhibitor of glycation which blocks the potential glycation sites (epsilon-NH2 groups). If glycation is a contributory factor, inhibition of glycation by acetylation should bring about a corresponding decrease in cataractogenic changes. We relied on in vitro glycation system and streptozotocin-diabetic rats to study the effects of ASA on lens crystallin glycation, thiol oxidation and aggregation. For in vitro studies, sterile lens soluble crystallin preparations from 1-month-old rats were incubated, under nitrogen, with 50 mM glucose and 20 mM ASA up to 15 days at 37 degrees C. To study the in vivo effect in diabetic rats, ASA feeding (200 mg/kg body wt/day) was initiated 1 week prior to streptozotocin administration, and sacrificed on 15, 30, 60 and 90 days after injection. The in vitro data show the inhibitory effect on glycation of ASA with all concentrations that were tested (5, 10, 20 mM ASA); the percentage inhibition increased with increasing ASA concentration and time. For example, with 50 mM glucose and 20 mM ASA incubated for 15 days, there was a significant decrease in glycation (P less than 0.05), thiol oxidation (P less than 0.05) and aggregation (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Swamy
M S
MS
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Abraham
E C
EC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002386:Cataract / Q000209:etiology / Q000517:prevention & control; D003459:Crystallins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D003459:Crystallins; D013311:Streptozocin; D005947:Glucose; D001241:Aspirin