[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.
Xiao
Tian-lin
TL
Eye Hospital, Wenzhou Medical College, Wenzhou Zhejiang 325027, China. tlxiao@yahoo.com
Shoeb
Mohammad
M
Ansari
Naseem H
NH
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000378:metabolism*; D048909:Diabetes Complications / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D000444:Aldehyde Dehydrogenase; C027576:4-hydroxy-2-nonenal