Histology and Cell Biology Department, Tanta University, Tanta, Egypt.
Anat Rec (Hoboken). 2021 Apr;304(4):714-724. doi: 10.1002/ar.24501. Epub 2020 Aug 21.
Sofosbuvir is a promising antiviral drug against chronic hepatitis C virus. Although it is characterized by its high efficacy, its adverse effects on nervous tissue are still unclear. Saffron is known for its neuroprotective property. This is a biochemical, histological and immunohistochemical study of the effect of sofosbuvir on the cerebellar cortex of rat and the possible ameliorating role of saffron's aqueous extract. Twenty-four adult male Wistar albino rats were equally divided into four groups; control, saffron extract-treated, sofosbuvir-treated (41.1 mg/kg/day for 6 weeks) and group concomitantly treated with saffron extract and sofosbuvir. Sofosbuvir-treated group recorded a significant increase in cerebellar malondialdehyde level coupling with a significant decrease in tissue glutathione and superoxide dismutase. Light microscopy revealed reduced number of Purkinje cells. The granular layer depicted many granular cells and Bergmann astrocytes with nuclear and cytoplasmic alterations. Electron microscopy revealed disorganized molecular layer with disarranged myelinated axons and disrupted mitochondria. Few shrunken Purkinje cells showed electron-dense cytoplasm and rarefied nuclei, indistinct nuclear envelope and dilated perinuclear space, areas of vacuolated cytoplasm, fragmented rough endoplasmic reticulum and few dark mitochondria. Some axons with tiny mitochondria were detected. A significant upregulation in immunohistochemical expression of GFAP-positive astrocytes was recorded. Concomitant administration of saffron extract significantly improved all studied parameters. Saffron extract is beneficial in ameliorating sofosbuvir-induced cerebellar morphological changes mainly through its antioxidant and neuroprotective properties.
索非布韦是一种有前途的抗慢性丙型肝炎病毒的抗病毒药物。尽管它具有高效的特点，但它对神经组织的不良反应仍不清楚。藏红花具有神经保护特性。这是一项关于索非布韦对大鼠小脑皮层影响的生化、组织学和免疫组织化学研究，以及藏红花水提物可能的改善作用。24 只成年雄性 Wistar 白化大鼠等分为四组；对照组、藏红花提取物处理组、索非布韦处理组（41.1mg/kg/天，持续 6 周）和同时给予藏红花提取物和索非布韦处理组。索非布韦处理组的小脑丙二醛水平显著升高，同时组织谷胱甘肽和超氧化物歧化酶显著降低。光镜下发现浦肯野细胞数量减少。颗粒层显示许多颗粒细胞和伯格曼星形胶质细胞，具有核和细胞质改变。电镜下显示分子层排列紊乱，有髓轴突排列紊乱，线粒体破坏。少数皱缩的浦肯野细胞表现出电子致密的细胞质和稀疏的核，核膜不明显，核周空间扩张，细胞质有空泡化，粗面内质网碎片化，线粒体较少。发现一些带有微小线粒体的轴突。GFAP 阳性星形胶质细胞的免疫组织化学表达显著上调。同时给予藏红花提取物可显著改善所有研究参数。藏红花提取物通过其抗氧化和神经保护特性，有利于改善索非布韦引起的小脑形态变化。
