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V. R. Kanth, K. Lavanya, T. N. Raju; Role of Indoleamine 2, 3-Dioxygenase in Pathogenesis of Streptozotocin-Induced Diabetic Cataract in Wistar Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2438.
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To study the role of indoleamine 2, 3-dioxygenase (IDO) in pathogenesis of streptozotocin-induced diabetic cataract in wistar rats.
Three month old male Wistar-NIN rats with average body weight of 220 ± 16g were obtained from National Center for Laboratory Animal Sciences (NCLAS), NIN, Hyderabad and randomly assigned into two groups. The group-A: control group (n=24) received 0.1 M citrate buffer, pH 4.5 (vehicle); the experimental rats, received a single i.p injection of streptozotocin (STZ) (32mg/kg) in 0.1 M citrate buffer, pH 4.5. After 72 h, fasting blood glucose levels were monitored and rats having blood glucose levels < 150mg/dl were excluded from the study. The rats with hyperglycemia were considered as group-B (n=24). All the rats had free access to food (AIN-93) and water. The Departmental Animal Ethics Committee had approved the animal care. Fasting blood glucose and body weights were monitored on weekly basis. To have better insight on the expression status of IDO during the on-set and maturation of cataract, rats were sacrificed at regular intervals of 15th, 30th, 45th and 60th day and reverse transcription-polymerase chain reaction performed. Semi-quantitative RT-PCR was carried out to study IDO expression in lenticular tissue of control and diabetic rats. whole lenticular tissue extract was used for analysis of MDA, GSH, Indoleamine 2,3-dioxygenase, tryptophan and kynurenines by HPLC method.
We have noticed a significant elevation in blood glucose levels throughout the experiment period and decrease in body weights. There was significant elevation in MDA and decrease in the levels of glutathione and its concomitant enzymes in cataractous lenses in relation to controls. We have noticed a significant elevation in mRNA levels of IDO in diabetic rats in relation to controls. Quantitative HPLC analysis studies revealed that tryptophan levels were raised in diabetic rats when compared to the control rats.
Hyperglycemic status caused lenticular opacification in streptozotocin-induced rats. This state caused the production of reactive oxygen species which had resulted in the rise in malonadialdehyde, protein carbonyl content and drop in glutathione and other attendant redox cycle enzymes. The rise in kynurenine in diabetic rats might be attributed to up-regulation of IDO gene and over production of IDO enzyme which cleaves the pyrrole ring of tryptophan and forms formylkynurenine using free oxy radicals. Hence it can be hypothesized that in diabetic cataract like aldose reductase; kynurenines also play a vital role in cataract formation.
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