Effect of the pyridoindole antioxidant stobadine on development of experimental diabetic cataract and on lens protein oxidation in rats: comparison with vitamin E and BHT.
OBJECTIVE
The aim of this study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on the development of diabetic cataract in rats. The findings were compared with the effect of the natural antioxidant vitamin E and the well known phenolic synthetic antioxidant butylated hydroxytoluene.


METHODS
Streptozotocin induced diabetic male Wistars rats were fed for 18 weeks a standard diet or a diet supplemented with stobadine (0.05% w/w), vitamin E (0.1% w/w), butylated hydroxytoluene (BHT, 0.4% w/w), or a mixture of stobadine (0.05% w/w) and vitamin E (0.1% w/w). The progress of cataract was monitored biweekly by ophthalmoscopic inspection. Plasma glucose and body weight were recorded regularly. At the end of the experiment, the content of free sulfhydryl and carbonyl was determined in total lens proteins and in the stobadine group plasma levels of malondialdehyde were also measured.


RESULTS
Long term treatment of diabetic animals with stobadine (STB), vitamin E, or BHT led to a marked delay in the development of advanced stages of cataract. At the end of the experiment, the visual cataract score was significantly decreased in the diabetic groups treated with stobadine or BHT, while vitamin E had no significant effect. Unexpectedly, combined treatment with STB+vitamin E advanced the progression of the higher stages of cataract, though without affecting the overall visual cataract score. Neither of the antioxidants exerted an effect on the glycemic state or body weight of the animals. Biochemical analyses of eye lens proteins showed significant diminution of sulfhydryl groups and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. Dietary supplementation with any of the antioxidants studied did not influence the levels of these biomarkers significantly. Nevertheless, in diabetic animals, stobadine supplementation significantly attenuated plasma levels of malondialdehyde, an index of systemic oxidative damage.


CONCLUSIONS
The results are in accordance with the postulated pro-oxidant role of chronic hyperglycemia, however, the direct oxidative free radical damage of eye lens proteins does not seem to be the key mechanism effective in the development of diabetic cataract. Sugar cataractogenesis appears to be a complex process, in which multiple mechanisms may be involved, including consequences of the overt oxidative stress in diabetes (e.g., protein modifying potential of toxic aldehydes generated as byproducts of carbohydrate autoxidation and lipid peroxidation). The ability of stobadine to attenuate lipoxidation reactions in diabetes may account, at least partly, for its observed anticataract action. Mechanisms involving reduction of mitochondrial damage by stobadine are also discussed.
Kyselova
Zuzana
Z
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.
Gajdosik
Andrej
A
Gajdosikova
Alena
A
Ulicna
Olga
O
Mihalova
Danica
D
Karasu
Cimen
C
Stefek
Milan
M
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002084:Butylated Hydroxytoluene / Q000378:metabolism*; D002243:Carbolines / Q000008:administration & dosage*; D002386:Cataract / Q000378:metabolism* / Q000503:physiopathology; D003459:Crystallins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D019587:Dietary Supplements; D018450:Disease Progression; D004338:Drug Combinations; D007908:Lens, Crystalline / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000378:metabolism*
D000975:Antioxidants; D001786:Blood Glucose; D002243:Carbolines; D003459:Crystallins; D004338:Drug Combinations; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D008315:Malondialdehyde; C100106:dicarbine