Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Anat Rec (Hoboken). 2023 Feb;306(2):422-436. doi: 10.1002/ar.24942. Epub 2022 May 2.
Sofosbuvir is a novel drug candidate for the treatment of hepatitis C viral infection; however, vision loss is one of its growing adverse effects. Saffron is a natural biomolecule with a high antioxidant potential that has been efficiently used in some diseases caused by oxidative stress. This study evaluated Sofosbuvir's neurodegenerative effect on the retina of albino rat and examined the potential protective role of saffron aqueous extract. Twenty-one adult male albino rats were randomly divided into three groups: Control, Sofosbuvir-treated (41.1 mg/kg /day for 6 weeks), and Sofosbuvir + Saffron co-treated groups. Retinal specimens were biochemically analyzed for malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, light and transmission electron microscopic examination, as well as immunohistochemical staining for Caspase-3, COX-2, and GFAP were performed. Sofosbuvir treatment caused a significant increase in retinal MDA, IL-6, and TNF-α levels coupling with a significant decrease in retinal total antioxidant capacity level. Histopathological findings revealed disturbed retinal architecture, detached pigment epithelium, vacuolated photoreceptors, in addition to a significant decrease in the thicknesses of both outer and inner nuclear layers, and the number of ganglionic cells. Ultrastructural examination revealed extensive degenerative changes in all retinal layers. Caspase-3, COX-2, and GFAP immunohistochemical expressions were significantly increased. Meanwhile, concomitant treatment with Saffron significantly improved retinal redox status, inflammation, histological, and ultrastructural parameters. Saffron may protect the retina from the hazardous effects of Sofosbuvir. Saffron could be used as an adjuvant therapy to protect patients receiving Sofosbuvir from retinal damage.
索非布韦是一种治疗丙型肝炎病毒感染的新型候选药物；然而，视力丧失是其日益严重的副作用之一。藏红花是一种天然生物分子，具有很高的抗氧化潜力，已在一些由氧化应激引起的疾病中得到有效应用。本研究评估了索非布韦对白化大鼠视网膜的神经退行性作用，并研究了藏红花水提物的潜在保护作用。21 只成年雄性白化大鼠随机分为三组：对照组、索非布韦处理组（41.1mg/kg/天，持续 6 周）和索非布韦+藏红花联合处理组。对视网膜标本进行丙二醛（MDA）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平的生化分析。此外，还进行了光镜和透射电镜检查，以及 Caspase-3、COX-2 和 GFAP 的免疫组织化学染色。索非布韦治疗导致视网膜 MDA、IL-6 和 TNF-α 水平显著升高，同时视网膜总抗氧化能力水平显著降低。组织病理学检查结果显示视网膜结构紊乱，色素上皮细胞分离，光感受器空泡化，以及外核层和内核层的厚度以及节细胞数量均显著减少。超微结构检查显示所有视网膜层均有广泛的退行性变化。Caspase-3、COX-2 和 GFAP 的免疫组织化学表达显著增加。同时，藏红花联合治疗显著改善了视网膜氧化还原状态、炎症、组织学和超微结构参数。藏红花可能保护视网膜免受索非布韦的有害影响。藏红花可作为辅助治疗，保护接受索非布韦治疗的患者免受视网膜损伤。
