Use of selenium to ameliorate doxorubicin induced hepatotoxicity by targeting pro-inflammatory cytokines
Use of selenium to ameliorate doxorubicin induced hepatotoxicity by targeting pro-inflammatory cytokines
复制标题
DOI：
10.1080/10520295.2020.1760353
复制
发表时间：
2020-05-10
影响因子：
1.6
通讯作者：
Yay, Arzu
中科院分区：
文献类型：
--
作者：
Cengiz, Ozge;Baran, Munevver;Yay, Arzu
多柔比星（DOX）是一种广泛应用的肿瘤治疗药物，但其肝毒性限制了其临床应用。与抗氧化剂一起施用DOX已成为预防DOX副作用的策略。虽然硒（Se）是一种重要的微量矿物质，但缺乏关于Se对DOX诱导的肝组织的影响的数据。本研究探讨了DOX肝毒性的机制及不同剂量硒对DOX肝损伤的保护作用。将雌性Wistar白化病大鼠分成8个相等的组。腹腔注射Se（i. p.）在第1、7、14、21和28天腹膜内注射5 mg/kg DOX后0.5 h，以0.5、1和2 mg的剂量给予大鼠。评估肝组织病理学以确定Se可以最好地抑制Dox诱导的肝毒性的剂量。此外，肿瘤坏死因子-α（TNF-α），白细胞介素-1 β（IL-1 β）的表达水平和增殖细胞核抗原（PCNA）的活性进行了测定，使用免疫组织化学。我们发现DOX引起肝损伤并增加TNF-α、IL-1 β和PCNA水平。硒可防止肝组织的结构损伤。我们的研究结果加强了硒在大鼠肝脏中的保护作用。
Doxorubicin (DOX) is a widely used drug for the treatment of cancer,but its clinical use is limited by its liver toxicity. Administering DOX with an antioxidant has become a strategy for preventing the side effects of DOX. Although selenium (Se) is an important trace mineral, data concerning the effect of Se on DOX induced liver tissue are lacking. We investigated the mechanism of DOX hepatotoxicity and the protective effect of different doses of Se on Dox induced liver damage. Female Wistar albino rats were divided into eight equal groups. Se was injected intraperitoneally (i.p.) to rats at doses of 0.5, 1, and 2 mg 0.5 h after injection i.p. of 5 mg/kg DOX on days 1, 7, 14, 21 and 28. Liver histopathology was assessed to determine the dose at which Se may best inhibit Dox induced liver toxicity,. Also, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) expression levels and proliferating cell nuclear antigen (PCNA) activity were determined using immunohistochemistry. We found that DOX caused liver damage and increased TNF-alpha, IL-1 beta and PCNA levels. Se prevented structural damage to liver tissues. Our findings reinforce the protective effects of Se in rat liver.