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Fundam Clin Pharmacol ; 32(6): 627-640, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29863796

RESUMEN

The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase-12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS-PAGE and UV absorption while changes in lenticular α-crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T-AOC, MDA, H2 O2 , and caspase-12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA-treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA-treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.


Asunto(s)
Catarata/inducido químicamente , Catarata/tratamiento farmacológico , Fructosa/farmacología , Cristalino/efectos de los fármacos , Estreptozocina/farmacología , Ácido Ursodesoxicólico/farmacología , Animales , Antioxidantes/metabolismo , Catarata/etiología , Catarata/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Insulina/metabolismo , Cristalino/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar
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