Metabolism and detoxification of the lipid derived aldehyde, 4-Hydroxynonenal in diabetic cataractogenesis in rat

Objective: To study the metabolism of 4-hydroxynonenal (HNE) one of lipid derived aldehydes (LDAs), in diabetic rat lens and its role in diabetic cataract formation. Methods: Experimental research. A factor design was used to set up the experiment statistically upon two factors: diabetic and normal control as treatment factors; day 30, 45 and 70 as the time factors. Normal and diabetic rats' lenses were incubated with HNE for 2 hours. HNE metabolites in the culture media were studied by high performance liquid chromatography(HPLC). Aldehyde dehydrogenase (ALDH) activity in normal and diabetic rat lens (30, 45 and 70 d after inducing of cataract) was detected by a spectrophotometer, ALDH protein and HNE-protein were detected by Western Blot. All data were analyzed by the Bonferroni test using SAS 8.0 software. Results: The major pathway for HNE metabolism in normal lens was conjugation with glutathione (GSH) to form GS-HNE (45%), followed by HNE's oxidation to 4-hydroxy-2-nonenoic acid (HNA) by ALDH, which accounted for approximately 9.1% of HNE. The conjugation of HNE with GSH in diabetic lens was decreased approximately 64% at day 30 compared with the controls(F = 49.59, P < 0.001). The pathway of HNE oxidation by ALDH in the diabetic lens was enhanced approximately 1.7 times at day 70 compared to day 30 (F = 11.51, P = 0.0442). A higher ALDH activity, greater amount of ALDH protein, and less amount of HNE-protein adduct were presented in diabetic rat lens. Conclusions: The pathway of conjugation of HNE with GSH is inhibited in diabetic lens which may play a role in the formation of diabetic cataract. The oxidation of HNE by ALDH is a compensation process for protecting the lens against diabetic damage.