Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of DL-alpha-lipoic acid

This study was designed to (1) evaluate retinal lipid peroxidation in early diabetes by the method specific for fi ee malondialdehyde and 4-hydroxyalk enals, (2) identify impaired antioxidative defense mechanisms and (3) asses s if enhanced retinal oxidative stress in diabetes is prevented by the pote nt antioxidant, DL-alpha-lipoic acid. The groups included control and strep tozotocin-diabetic rats treated with or without DL-alpha-lipoic acid (100 m g kg(-1) day(-1), i.p., for 6 weeks). All parameters were measured in indiv idual retinae. 4-Hydroxyalkenal concentration was increased in diabetic rat s (2.63 +/- 0.60 vs. 1.44 +/- 0.30 nmol/mg soluble protein in controls, P < 0.01), and this increase was prevented by DL-alpha-lipoic acid (1.20 +/- 0 .88, P < 0.01 vs, untreated diabetic group). Malondialdehyde, reduced gluta thione (GSH) and oxidized glutathione (GSSG) concentrations were similar am ong the groups. Superoxide dismutase. glutathione peroxidase (GSHPx), gluta thione reductase (GSSGRed) and glutathione transferase (GSHTrans) activitie s were decreased in diabetic rats vs. controls. Quinone reductase was upreg ulated in diabetic rats, whereas catalase and cytoplasmic NADH oxidase acti vities were unchanged. DL-alpha-Lipoic acid prevented changes in superoxide dismutase and quinone reductase activities induced by diabetes without aff ecting the enzymes of glutathione metabolism. In conclusion, accumulation o f 4-hydroxyalkenals is an early marker of oxidative stress in the diabetic retina. Increased lipid peroxidation occurs in the absence of GSH depletion , and is prevented by DL-alpha-lipoic acid. (C) 2000 Elsevier Science B.V. All rights reserved.