INCREASED SUSCEPTIBILITY TO METAL-CATALYZED OXIDATION OF DIABETIC LENS BETA(L) CRYSTALLIN - POSSIBLE PROTECTION BY DIETARY SUPPLEMENTATION WITH ACETYLSALICYLIC-ACID

The effect of dietary supplementation with acetylsalicylic acid on the increased modification, and susceptibility to modification, of lens crystallins from the streptozocin diabetic rat, has been determined. This was done by the measurement of characteristic markers of protein post-translational oxidative modification and glycation, in βL crystallins purified from the lenses of control, diabetic and acetylsalicylic acid-supplemented diabetic animals, with no further manipulations, and again following the application of an in vitro graded oxidative insult. Crystallins prepared from the diabetic, in comparison with control animals, exhibited a higher level of bityrosine- and AGEP-like fluorescence as well as a loss of tryptophan fluorescence and sulphydryl groups. Exposure to an oxidative insult (in the form of CuSO4 and ascorbate) increased all parameters in βL crystallins, irrespective of their source. However, the effects were most pronounced in the diabetic in which the effects of oxidative stress were always greater than the control crystallin. Dietary supplementation of the diabetic group with acetylsalicylic acid (100 mg kg-1 body weight day-1) had a marked effect in decreasing the level of modification induced in diabetic crystallins, by in vitro metal catalysed oxidative stress, lowering the levels of AGEP- and bityrosine-like fluorescence and carbonyl group formation. Increasing the oxidative stress by addition of increasing concentrations of H2O2, induced stress proportional increases in the indicators of protein modification in all βL crystallins, irrespective of source. The increase in damage in relation to H2O2 concentration was greater in those crystallins from diabetic animals, revealing a greater susceptibility to such oxidative stress. This increase in susceptibility to stress was partially alleviated by dietary supplementation with acetylsalicylic acid, which restored the rate at which bityrosine- and AGEP-like fluorescence accumulated, towards that evident in the control. The results are discussed in relation to the proposal that acetylsalicylic acid can prevent some of the effects of diabetes, and the increased post-translational modification of crystallins from diabetic animals when subjected to oxidative stress, a factor implicated in cataractogenesis. © 1993 Academic Press. All rights reserved.