| Cataract is one of the major causes of blindness worldwide. It is estimated that a delay in cataract formation of about 10 years would reduce the prevalence of visuality disabling cataract by about 45%. Such a delay would enhance the quality of life for much of the world's older and diabetic population and substantially diminish both the economic burden due to disability and surgery related to cataract. Diabetes is one of the most important risk factor for cataract and cataractogenesis is one of the earliest secondary complications of diabetes mellitus. Since extracellular glucose diffuses into the lens uncontrolled by the hormone insulin, the lens is one of the body parts most affected in diabetes. Possible pathophysiological mechanisms include non-enzymatic glycosylation with cross linking of proteins, oxidative stress, and activation of the polyol pathway causing increased hydration. Multiple mechanisms have been implicated in the development of cataract in diabetes. To date, the exact sequence of events that leads to opacification has not been clearly defined. Thus, the relationship of the opacity to the initiating event may be obscure.Many anti-cataractogenic agents, such as aldose reductase inhibitors, have been described so far, but owing to lack of success in patients, no drug has yet been approved for clinical use. Evidence from epidemiological, in vitro and animal studies has accumulated to support the idea that aspirin and carnosine protect against cataract. Camosine is a naturally occurring, water-soluble dipeptide. It has antioxidant and antiglycating properties,and may be a potential therapeutic agent mainly due to its antioxidant and antiglycating activities. Aspirin (acetylsalicylic acid) is a commonly used analgesic that protects against the formation of diabetic cataract. It may protect against glycation. Aspirin has been shown to reduce glycation in vitro, and in animal experiments, probably by acetylation of amino groups, and it also may inhibit glycoxidation and AGE-cross-link formation, therefore its effects may be because of its ability to act as a free radical scavenger and metal ion chelator.Previously, we have shown that diabetic cataract in rats could be prevented by carnosine or aspirin in aqueous solution, which readily penetrated sololy into the eye after topical administration without producing plasma drug levels that could lead to systemic side effects. On the basis of the properties of carnosine and aspirin mentioned above, we assumed that a combination of carnosine and aspirin eye drops could be more effective than either of them alone.Glutathione (GSH) is involved in many cellular functions including scavenging free radicals and other reactive species, regulation of DNA and protein synthesis, signal transduction, cell-cycle regulation, proteolysis, immune response and cytokines, as well as in various metabolic pathways. Changes of glutathione in lens, cornea, retina and other eye tissues, occur with ageing, cataract, diabetes, irradiation and administration of some drugs.PURPOSE:1. To investigate the effect of combination of carnosine and aspirin eye drops on the progression in diabetic cataract formation induced by streptozotocin (STZ).2. To investigate the effect of combination of carnosine and aspirin eye drops on the change of the thiols (from GSH and protein) in the lens, cornea and retina of the diabetic rats.METHODS: Sprague-Dawley (SD) rats were selected and diabetes was induced by injection of streptozotocin (65 mg/kg body weight, intraperitoneally). The control group (Group A) received only injection of vehicle. The others randomly divided into four groups (Group B-E). The untreated group (Group B) rats received only the vehicle solution. The Group C and D animals were treated by instillation of one drop of 1% carnosion eye drops and 0.05% aspirin eye drops, respectively, in both eyes twice a day for a period of 8 weeks. While the Group E rats were treated alternately by carnosine 1% and aspirin 0.05% eye drops, one drop, twice daily. Cataract progression due to diabetic was monitored by slit lamp microscope and classified into seven stages. At the end of 8 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract, including thiols (from glutathione and protein), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT) and water-solution proteins content in the lens were investigated. Then the corneas and retinas were removed for measurement of the thiols (from glutathione and protein). Blood glucose levels, body weights, food intake, were also determined.RESULTS: About 84.4% of the rats responded to the STZ injection (blood glucose measured >14mmol/L). The stage of cataract of lenses among all the groups was different (P<0.001) in the study. Moreover, there was significantly statistical difference between the untreated diabetic animals and the treated diabetic animals (P<0.05), between the combination group and aspirin group (P=0.04) after 7 weeks. In the 8th week, although the stage of lens opacification in the combination group was more conspicuous than in the carnosine group, no significantly statistical difference was found between them. The food and water intake in all the diabetic groups increased compared with the normal group, and so did the urine volume and the urine glucose. The blood glucose and urine glucose in diabetic rats were statistically higher than that of the normal rats (P<0.05). Also, the body weight of diabetic rats was statistically significant lower than that of the normal rats (P<0.05). There was a significant decrease in water-soluble protein in the diabetic groups compared with the control group (P<0.05). However, the three treatments improved the soluble protein levels, and the combination treatment improved more than the others. The levels of thiols (from GSH and protein) were decreased in the lens of diabetic rats (P<0.05). However, there was no significantly statistical difference between the control group and the combination group. In addition, the increased specific activity of GPx and decreased activity of GR and CAT further substantiate the role of oxidative stress in cataractogenesis due to hyperglycemia, though there was no significantly statistical difference in activity of GR of all the groups.The levels of thiols (from GSH and protein) were decreased in the lens of diabetic rats (P<0.05). However, there was no significantly statistical difference between the control group and the combination group.In the retina, the levels in the carnosine group and the aspirin group were increased as compared with the normal group, and there was significantly statistical difference between them, also between the two groups and the untreated group (P<0.05). While the levels were decreased in the combination group comparing to the normal control group and the untreaded group, but no difference could be found.Then in the cornea, the levels went up in carnosine group, though they were declined in the other diabetic groups. Moreover, there was statistically significant difference between the carnosine group and the untreated group (P<0.05).CONCLUSIONS: The results indicated that the combination of carnosine and aspirin eye drops are effective against the onset and development of diabetic cataract in rats. Most important, the effect of combination eye drops is better than the aspirin eye drops, while, just in the changes of biochemical indicator, better than the carnosine eye drops. Moreover, diabetes would decline the levels of thiols (from GSH and proteins) in eye tissues, and the eye drops in our study might have a certain protection for the diabetic eyes.
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