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CO Q10 对长春新碱诱导的周围神经病变的可能保护作用:针对氧化应激、炎症和 Sarmoptosis。

Possible protective effects of CO Q10 against vincristine-induced peripheral neuropathy: Targeting oxidative stress, inflammation, and sarmoptosis.

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.

Department of Phramacology, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

J Biochem Mol Toxicol. 2022 Mar;36(3):e22976. doi: 10.1002/jbt.22976. Epub 2021 Dec 23.

Abstract

Vincristine is a chemotherapy drug that belongs to the vinca alkaloids group. It is used for treatment of hematologic malignancies and several solid tumors. Vincristine-induced peripheral neuropathy is a major dose-limiting side effect. Coenzyme Q10 (Co Q10), an essential component of the mitochondrial electron transport chain, participates in energy production. It is a powerful fat-soluble antioxidant and also exerts anti-inflammatory effects. Therefore, this study was aimed to focus on the mechanistic insights of vincristine-induced peripheral neuropathy in addition to shedding the light on the modulatory effect of Co Q10. Twenty-eight rats were randomly divided into four groups. Peripheral neuropathy was induced by intraperitoneal injection of vincristine (0.1 mg/kg body weight). Co Q10 was injected intraperitoneally (10 mg/kg body weight) for 24 days. Sciatic nerve MDA, TAC, GSH, 8-OHdG, TNF-α, IL-1β, and NF-κB levels were assessed. Gene expression of SARM1 and Nrf2 was also assessed. Serum neurofilament light chain was immunoassayed, in addition to the behavioral assessment. Co Q10 significantly improved oxidative stress and inflammatory biomarkers. It also decreased serum NFL levels. It enhanced Nrf2 and decreased SARM1 gene expression. Histopathological findings proved the biochemical and molecular findings. Our results support Co Q10 as a potential protective agent against vincristine-induced peripheral neuropathy.

摘要

长春新碱是一种化疗药物,属于长春碱类。它用于治疗血液系统恶性肿瘤和几种实体瘤。长春新碱引起的周围神经病变是主要的剂量限制副作用。辅酶 Q10(Co Q10)是线粒体电子传递链的重要组成部分,参与能量产生。它是一种强大的脂溶性抗氧化剂,也具有抗炎作用。因此,这项研究旨在关注长春新碱引起的周围神经病变的机制见解,并阐明 Co Q10 的调节作用。28 只大鼠随机分为四组。通过腹腔注射长春新碱(0.1mg/kg 体重)诱导周围神经病变。腹腔注射 Co Q10(10mg/kg 体重)24 天。评估坐骨神经 MDA、TAC、GSH、8-OHdG、TNF-α、IL-1β 和 NF-κB 水平。还评估了 SARM1 和 Nrf2 的基因表达。免疫测定血清神经丝轻链,并进行行为评估。Co Q10 显著改善氧化应激和炎症生物标志物。它还降低了血清 NFL 水平。它增强了 Nrf2 并降低了 SARM1 基因表达。组织病理学发现证明了生化和分子发现。我们的结果支持 Co Q10 作为一种潜在的保护剂,可预防长春新碱引起的周围神经病变。

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