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Abstract Diabetic retinopathy (DR) is a major consequence of diabetes on the microvascular system which affect retinal vasculature and results in retinal damage leading to vision loss. Therefore, it would seem important to find therapeutic alternatives to the current treatments that are available, as they do not ensure a speedy and complete reparative process. Antioxidants therapy is an attractive approach for treatment of many degenerative diseases. Selenium is an essential trace element which possess antioxidant effect. Selenium antioxidant and anti-inflammatory activities are probably responsible for its efficiency in the treatment of diseases with oxidative stress. Selenium has organic and non-organic forms with low bioavailability, solubility, and adherence properties. Thus, introducing nanoparticles into Se is highly recommended to maximize its effects on a health status. With their superior biological activity, low toxicity, and bioavailability, selenium nanoparticles (SeNPs) offer a purported compromise between toxicity profiles and therapeutic potential through nanotechnology. Several investigations have demonstrated that these SeNPs are three to seven times less harmful than selenium compounds or organic selenium and are effective antioxidants. This study was concerned with determination of biochemical, histological and immunohistochemical changes in adult male albino rats with STZ-induced DR and studying the possible ameliorating effect of Selenium versus Nanoselenium and the possible involved mechanisms. In this study, 60 adult male albino rats weighting approximately 150-250 gm of 8-10 weeks were used; divided randomly into 6 groups and each group contained 10 rats. 1- control group: Rats received a daily dose of the standard diet and distilled water 2- Se +ve group: Rats received 2 mg/kg/day of selenium tablets dissolved in 2 ml of distilled water . 3- NS +ve group : Rats received 0.5mg/kg/day nano-selenium dissolved in 2 ml of distilled water. 4- DR group: Rats were rendered diabetic with a single intraperitoneal injection of STZ (45 mg/kg). 4- DR-Se treated group: the diabetic rats received 2mg/kg/day selenium tablets dissolved in 2 ml of distilled water for 4 weeks. 5- DR-NS treated group: the diabetic rats received 0.5 mg/kg/day nano-selenium dissolved in 2 ml of distilled water for 4 weeks. The results of the current study revealed that: • The mean level of blood glucose: DR group showed significant increase in blood glucose level if compared to control groups while DR-Se and DR-NS treated group showed significant decrease if compared to DR group. • Retinal oxidative stress markers: Retinal tissue in DR-group indicated oxidative stress (significant increase in MDA levels compared to control groups) with defective antioxidant mechanisms (significant decrease in TAC compared to control groups). With Se and NS treatment, retinal tissue revealed attenuated oxidative stress (significant decrease in MDA compared to DR-group) with antioxidant mechanism activation (significant increase in TAC compared to DR-group). • Retinal levels of TLR-4: DR-group showed a significant increase in TLR-4 levels compared to control groups. However, DR-Se and DR-NS treated groups, this parameter decreased compared to DR-group. • In Hematoxylin and Eosin-stained sections: DR- group showed marked morphological changes in the form of significant decreased retinal thickness with loss of normal retinal architecture. In addition, there were photoreceptors disorganization, neuronal loss and degeneration in the outer nuclear layer, inner nuclear layer and ganglion cell layer, and highly vacuolated inner plexiform layer. Administration of Se in DR-Se treated group resulted in partial restoration of normal retinal thickness, retinal layers and photoreceptors’ organization and administration of Se-NPs in DR-NS treated group resulted in complete restoration of retinal thickness and organization of layers similar to control groups. • VEGF immunohistochemical study showed significant increase in the VEGF immunoreactivity in DR- group compared to control groups. However, Se and NS administration caused significant decrease in the immunoreactivity compared to DR-group. • NF-κB p65 immunohistochemical study showed significant increase in the NF-κB immunoreactivity in DR- group compared to control groups. While NS treatment in DR-NS treated group caused significant decrease compared to DR-group. Meanwhile, DR-Se treated group still showed significant increase compared to control groups. • GFAP immunohistochemical study showed significant increase in GFAP immune-reactivity (indicating Astrocytes and Müller cells) in DR-group compared to control groups and significant decrease of GFAP immune-reactivity in DR-NS treated group compared to DR group. Meanwhile, DR-Se treated group still showed significant increase compared to control groups. • Connexin-43 immunohistochemical study showed significant decrease in Connexin43 immune-reactivity in DR group compared to control groups and significant increase of Connexin 43 immune-reactivity in DR-Se and DR-NS treated groups compared to all previous groups. It was concluded that Nano selenium has ameliorating effects on STZ induced damaging effect on retinal tissue. Recommendations • Further investigations are needed to study the effect of selenium nanoparticles in the treatment of other models of retinal injury. • Further investigations are needed to introduce selenium nanoparticles in the treatment of retinal injury under clinical trials. • Investigate the safety of using this nanoparticles in different disease models. |