Abstract
Purpose: :
To investigate the role kynurenines in the pathogenesis of cataract with reference to tryptophan deficient regimen in wistar rats.
Methods: :
Male Wistar–NIN rats of weanling age (21–24 days) of an avg. body weight 35–40g, were randomly assigned into three groups. Diet composition of each group is as follows: Gr.–A: control (n=12); Gr–B: marginal–tryptophan supplemented (0.05% trp. /100gm diet) (n=15); Gr.–C: tryptophan–deficient group (n=20). The Departmental Animal Ethics Committee has approved the animal care. The experiment was carried out for three months. At the end of the experimentation biochemical investigations were carried out for antioxidant status and tryptophan metabolites using reverse phase HPLC.
Results: :
Decrease in body weight and organ development in the deficient animals was noticied and these changes were not seen in the rats that recevived 0.05% tryptophan. Slit–lamp biomicroscopy examination revealed that the rats that restricted with protein diet showed corneal vascularisation with drying of ocular tissue by the end of 3–4 weeks; by the end of 6–7 weeks there are ‘Y’ sutures, which became more prominent with punctuate opacities. By the end of experimentation ∼ 30% of lens have developed frank nuclear cataracts and ∼ 53% have hazy lens with punctuate opacification.
However, marginal–tryptophan feeding attenuated the opacification of the lens. Biochemical studies revealed that there is a decrease in protein content, reduced glutathione (GSH), anti–oxidant enzyme levels and tryptophan–fluorescence in Gr–III rats. There was an increase in lipid peroxidation and AGE–fluorescence suggesting the oxidative stress due to protein deficiency. However, in Gr.II rats,there was an increase in protein content, glutathione and antioxidant enzyme levels,tryptophan–fluorescence and inhibition in AGE–fluorescence and lipid peroxidation.In the tryptohan deficient animals the enzymatic degradation of tryptophan by IDO has been significantly reduced and therefore, it decreased the anti–oxidative effects of IDO itself. In addition to this there was also a reduction in the formation of tryptophan–degraded products. There was an impairment in the synthesis of formylkynurenine, which influences enzymatic and non–enzymatic degradation of tryptophan in which processes oxygen radicals are scavenged.
Conclusions: :
– Our findings suggest that tryptophan supplementation to protein deficient animals has a definite protective influence as revealed in the activity levels of antioxidant enzymes in relation to the tryptophan deficient animals.<
Keywords: cataract • antioxidants • oxidation/oxidative or free radical damage