In the present study, the protective effects of quercetin on peripheral neurotoxicity caused by vincristine, which is used effectively in the treatment of various types of cancers, were investigated by using different techniques. In the study, for 12 days, male Sprague Dawley rats were given 25 and 50 mg/kg doses of quercetin orally and were administered a 0.1 mg/kg dose of vincristine (a total cumulative dose of 1.2 mg/kg) intraperitoneally 30 min later. The protein levels of nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase-1 (NQO1), glial fibrillary acidic protein (GFAP), and nuclear factor kappa B (NF-κB) were measured with ELISA; the immunopositivity of 8-hydroxy-2′-deoxyguanosine (8−OHdG) and caspase 3 were determined with immunohistochemistry; the mRNA transcript levels of double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK), inositol-requiring enzyme-1 (IRE1), activating transcription factor-6 (ATF-6), glucose-regulated protein 78 (GRP78), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase 3, protein kinase B1/2 (Akt-1/2), and forkhead box transcription factor, class O1 (FOXO1) were determined with RT-PCR. The reduction of Nrf2 levels and HO-1 and NQO1 activities in the sciatic nerve tissue, the increase in the levels of 8−OHdG, and the increase in the levels of GFAP and NF-κB caused by vincristine was observed to cause oxidative stress, oxidative DNA damage, neuronal cell damage, and inflammation, respectively. Additionally, vincristine was determined to cause ER stress and apoptosis by increasing PERK, IRE1, ATF-6, and GRP78 and caspase 3 and Bax expressions and by decreasing Bcl-2 expressions. Vincristine causing Akt inhibition also shows that it prevents neuronal survival. However, quercetin was determined to relieve oxidative stress, oxidative DNA damage, neuronal cell damage, inflammation, ER stress, and apoptosis caused by vincristine and enable Akt activation. These results show that in rats, quercetin may have a protective effect against peripheral neurotoxicity caused by vincristine.

在本研究中，槲皮素对长春新碱引起的外周神经毒性的保护作用进行了研究，长春新碱有效地用于治疗各种类型的癌症，使用不同的技术进行了研究。在该研究中，雄性 Sprague Dawley 大鼠口服 25 和 50 毫克/公斤剂量的槲皮素，并在 30 分钟后腹腔注射 0.1 毫克/公斤剂量的长春新碱（总累积剂量为 1.2 毫克/公斤），为期 12 天。 . 核因子红细胞 2 相关因子 2 (Nrf2)、血红素加氧酶-1 (HO-1)、NAD(P)H 醌脱氢酶-1 (NQO1)、胶质纤维酸性蛋白 (GFAP) 和核用ELISA测量因子κB（NF-κB）；8-羟基-2'-脱氧鸟苷（8-OHdG）和半胱天冬酶3的免疫阳性用免疫组化法测定；双链 RNA 活化蛋白激酶 (PKR) 样 ER 激酶 (PERK)、肌醇需要酶-1 (IRE1)、激活转录因子-6 (ATF-6)、葡萄糖调节蛋白 78 的 mRNA 转录水平(GRP78)、Bcl-2 相关 X 蛋白 (Bax)、B 细胞淋巴瘤-2 (Bcl-2)、半胱天冬酶 3、蛋白激酶 B1/2 (Akt-1/2) 和叉头盒转录因子，类O1 (FOXO1) 用 RT-PCR 测定。观察到坐骨神经组织中 Nrf2 水平和 HO-1 和 NQO1 活性的降低，8-OHdG 水平的增加以及长春新碱引起的 GFAP 和 NF-κB 水平的增加引起氧化应激，氧化性 DNA 损伤、神经元细胞损伤和炎症。此外，长春新碱通过增加 PERK、IRE1、ATF-6、和 GRP78 和 caspase 3 和 Bax 表达以及通过降低 Bcl-2 表达。长春新碱引起 Akt 抑制也表明它会阻止神经元存活。然而，槲皮素被确定可以缓解由长春新碱引起的氧化应激、DNA 氧化损伤、神经元细胞损伤、炎症、内质网应激和细胞凋亡，并使 Akt 活化。这些结果表明，在大鼠中，槲皮素可能对长春新碱引起的外周神经毒性具有保护作用。