الفهرس 
Introduction and Literature ReviewOnly 14 pages are availabe for public view
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Abstract
The absolute clarity of the lens of the eye is vital in the visual system. The unique structural and physiological properties of the lens are tightly integrated with highly ordered protein content to allow the lens to remain transparent. Consequently, any alteration or disturbance of these highly-ordered proteins can affect the optical properties of the lens.
Cataract is a degenerative condition and results from the loss of crystalline lens transparency. It is one of the major causes of visual impairment globally and the first cause of blindness. Delaying the onset of cataracts by pharmacological means may help to bridge the gap between the high incidence of cataract blindness and the provision of surgical treatment.
Since oxidative stress and calcium ions overload have been identified as the major two players in the causation of cataract. Hence, the present study was designed to evaluate the potential attenuating effect of caffeine, nifedipine and the combination of them on sodium selenite-induced cataract in albino Wistar rats.
One hundred and fifty healthy albino Wistar rats were divided into 5 groups; the first group (Con group) received intraperitoneal injection of saline and served as control, 2nd group (Sel group) received a single subcutaneous injection of 30 nmol/g body weights of sodium selenite to induce cataract. 3rd and 4th groups (Sel+Caf and Sel+Nif) received intraperitoneal injection of 5.15 μmoles of caffeine and 0.1 mg/kg of nifedipine respectively, starting two days prior to the administration of sodium selenite and continuing such treatment till the end of experiment. Last group (Sel+Caf+Nif) got the combined treatments of caffeine and nifedipine in the same regimen. All groups were decapitated after 5, 15 and 25 days of sodium selenite injection.
Cataract induced by sodium selenite and anti-cataractogenic effect of caffeine and/or nifedipine were evaluated for 5, 15 and 25 days by measuring of Na+-K+ATPase activity which was carried out on the lens membrane, estimation of total soluble lens proteins, measurement of refractive index for lens proteins and determination of calcium concentration in lens. Besides, the molecular weight characteristics of the soluble lens proteins samples are presented by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and then subjected to curve narrowing procedure that combines Fourier deconvolution and nonlinear curve fitting. Additionally, the comet assay was used to examine qualitative and quantitative variations in DNA of lens epithelium. Analysis of variance was used with significance level set at P< 0.05.
The results of all selenite groups indicated a very highly significant decrease (P˂0.001) in Na+-K+ATPase activity with maximum percentage change relative to control -34% after 5 days and the total soluble lens protein content reached to -55% after 25 days. Meanwhile, there is a very highly significant increase (P˂0.001) in the calcium lens content and the refractive index to reach its maximum percentage increase 386% and 0.55 % respectively, after 25 days. The analysis of all comet assay parameters (percentage tailed cells, tail length, percentage tailed DNA, and tail moment) also showed a very highly significant increase (P˂0.001) after all periods of injection of sodium selenite. Also, very high significant changes (p˂0.001) in the molecular weight and area under peaks were estimated in profile of electrophoretic mobility of lens proteins.
After caffeine treatment, the Na+-K+ATPase activity still suffered from the reduction but only with highly significant decrease (P˂0.01) for 15 and 25 days and the percentage change reduced to -8% and -6% respectively from the selenite groups. Also, the total soluble lens protein revealed a significant decrease (p˂0.05) for 25 days and the percentage change reached -4%. The calcium content increased with a high significant difference (p˂0.01) after 15 and 25 days but percentage change reduced to 66% and 58%. While, the refractive index values characterized with a high significant increase (p˂0.01) but the percentage change reduced to 0.10% for 5 days. The values of the tail moment, one of comet assay parameters, for the group decapitated after 25 days was increased by a high significant difference (p˂0.01) compared to control.
For nifedipine groups, the Na+-K+ATPase activity and the total soluble lens protein content were decreased with a significant difference (p˂0.05) and the percentage changes reached to -4% and -3% respectively, for group decapitated after 25 days. The calcium content showed a significant increase (p˂0.05) with percentage change 43% for the same group. The percentage change of refractive index reduced to 0.08%, 0.15% and 0.17 for 5, 15 and 25 days respectively compared to effect of sodium selenite. The tail moment value for the group treated with nifedipine for 25 days was increased by a high significant difference (p˂0.01) compared to control.
The protection effects of administration with the combination treatment had been proved after 15 and 25 days by the absence of any significant changes in the Na+-K+ATPase activity (with percentage difference -3% and -2%), the total soluble lens protein (with percentage difference -2% and -3%) and calcium content (with percentage difference 17% and 26%) and control groups. Meanwhile, the refractive index values for groups decapitated after 5 and 25 days of sodium selenite injection showed no differences (with percentage difference 0.05% and 0.04%) with the control values. The analysis comet assay parameters for groups decapitated after 5 and 25 days ascertained the attenuation effect of caffeine and nifedipine treatment by the absence of any significance difference with control for all comet assay parameters except the tail moment which showed only a significant increase (p˂0.05).
All changes in the molecular weight and area under peaks estimated in profile of electrophoretic mobility of lens proteins occurred in the selenite groups were reduced markedly not only in groups treated with caffeine but also in the groups treated with nifedipine. However, the damaging effect of sodium selenite injection was complete counteracted by the treatment with combination of caffeine and nifedipine, therefore protection against cataractogenesis was ascertained in these groups.
In conclusion, according to these results oxidative hypothesis of cataract formation, reactive oxygen species can damage lens proteins and lens membrane. Therefore, nutrients with antioxidant capabilities can potentially delay against these changes such as caffeine but blockade of L-type calcium channels in the lens are needed as nifedipine to complete protection from cataractogenesis.