ABSTRACT

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-α (TNF-α), interleukin-1β (IL-1β) expression levels and proliferating cell nuclear antigen (PCNA) activity were determined using immunohistochemistry. We found that DOX caused liver damage and increased TNF-α, IL-1β and PCNA levels. Se prevented structural damage to liver tissues. Our findings reinforce the protective effects of Se in rat liver.

摘要

多柔比星（DOX）是一种广泛用于治疗癌症的药物，但其临床应用受到其肝毒性的限制。将 DOX 与抗氧化剂一起给药已成为预防 DOX 副作用的一种策略。尽管硒 (Se) 是一种重要的微量矿物质，但缺乏有关硒对 DOX 诱导的肝组织影响的数据。我们研究了 DOX 肝毒性的机制和不同剂量 Se 对 Dox 诱导的肝损伤的保护作用。雌性 Wistar 白化大鼠被分成 8 个相等的组。在第 1、7、14、21 和 28 天 ip 注射 5 mg/kg DOX 后 0.5 小时，以 0.5、1 和 2 mg 的剂量向大鼠腹膜内 (ip) 注射 Se。评估肝脏组织病理学以确定剂量在这种情况下，Se 可以最好地抑制 Dox 诱导的肝毒性。此外，肿瘤坏死因子-α（TNF-α），使用免疫组织化学测定白细胞介素-1β (IL-1β) 表达水平和增殖细胞核抗原 (PCNA) 活性。我们发现 DOX 引起肝损伤并增加 TNF-α、IL-1β 和 PCNA 水平。硒防止了对肝组织的结构性损伤。我们的研究结果加强了硒对大鼠肝脏的保护作用。