Resveratrol Ameliorates Hydroxychloroquine-Induced Retinopathy by Autophagy Induction: Molecular and Morphological Evidences

Abdelfadeel, Karima F.; Abdel Hamid, Omaima I.; Alazouny, Zeinab M.

doi:10.21608/zumj.2022.132439.2546

Resveratrol Ameliorates Hydroxychloroquine-Induced Retinopathy by Autophagy Induction: Molecular and Morphological Evidences

Document Type : Original Article

Authors

¹ Medical Histologydepartment,faculty of medicine,zagazig university

² Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Egypt.

10.21608/zumj.2022.132439.2546

Abstract

Introduction: Hydroxychloroquine (HCQ) has been utilized globally for about 75years initially as antimalarial drug, however, its uses expanded to include autoimmune diseases. It is being investigated for their potential to treat coronavirus disease. The widespread use and self-treatment led to concerns of potential harms from toxicities. Retinopathy is considered the major dose-limiting toxicity of HCQ. Aim of Work: to explore the potential ameliorative effect of resveratrol on HCQ-induced retinopathy in rats. Materials and Methods: Fifty adult male rats randomly assigned to 3 groups, control, HCQ-treated group received hydroxychloroquine sulfate 62mg/kg/day and HCQ&resveratrol-treated group treated with hydroxychloroquine sulfate 62mg/kg/day and resveratrol 20mg/kg/day. After the termination of 12 weeks of dosing, serum of rats were used for estimation of caspase-3, tumor necrosis factor-alpha (TNF-α), oxidative stress parameters malondialdehyde (MDA), protein carbonyl, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and total antioxidant capacity (TAC). The rats were sacrificed and retinas were isolated for detection of gene expression of mammalian target of rapamycin (mTOR), Microtubule-Associated Protein-1 Light Chain-3 (LC3B), Beclin-1 and p62 using qRT-PCR, histopathological, ultrastructural and immunohistochemical expression of Bcl-2. Results: HCQ treatment led to significant increase in caspase-3, TNF-α, (MDA), protein carbonyl, 8-OHdG with significantly decreased TAC. The significantly increased expression of mTOR led to autophagy inhibition manifested as significant reduction of LC3B, Beclin-1 expression and a significantly increased p62 expression. There were many retinal pathological changes including decrease retinal thickness with disorganization, vaculation, pyknosis and diminished cell population. Concurrent treatment with resveratrol induced an obvious improvement of retinal pathology through antioxidant and autophagy inducing effect.

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