Alanezi Abdulkareem A, Almuqati Afaf F, Alfwuaires Manal A, Alasmari Fawaz, Namazi Nader I, Althunibat Osama Y, Mahmoud Ayman M
Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Oct 24;15(11):1310. doi: 10.3390/ph15111310.
Cisplatin (CIS) is an effective chemotherapeutic agent used in the treatment of several malignancies. The clinical use of CIS is associated with adverse effects, including acute kidney injury (AKI). Oxidative stress and inflammation are key events in the development of CIS-induced AKI. This study investigated the protective effect of taxifolin (TAX), a bioactive flavonoid with promising health-promoting properties, on CIS-induced nephrotoxicity in mice. TAX was orally given to mice for 10 days and a single dose of CIS was injected at day 7. Serum blood urea nitrogen (BUN) and creatinine were elevated, and multiple histopathological alterations were observed in the kidney of CIS-administered mice. CIS increased renal malondialdehyde (MDA), nitric oxide (NO), nuclear factor-kappaB (NF-κB) p65, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and decreased cellular antioxidants in mice. TAX remarkably prevented kidney injury, ameliorated serum BUN and creatinine, and renal MDA, NO, NF-κB p65, and pro-inflammatory cytokines, and boosted antioxidant defenses in CIS-administered mice. TAX downregulated Bax and caspase-3, and upregulated Bcl-2. These effects were associated with upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression and heme oxygenase (HO)-1 activity in CIS-administered mice. In conclusion, TAX prevented CIS-induced AKI by mitigating tissue injury, oxidative stress, inflammation, and cell death. The protective efficacy of TAX was associated with the upregulation of Nrf2/HO-1 signaling.
顺铂（CIS）是一种用于治疗多种恶性肿瘤的有效化疗药物。CIS的临床应用与不良反应相关，包括急性肾损伤（AKI）。氧化应激和炎症是CIS诱导的AKI发生发展中的关键事件。本研究调查了具有良好健康促进特性的生物活性类黄酮紫杉叶素（TAX）对CIS诱导的小鼠肾毒性的保护作用。给小鼠口服TAX 10天，并在第7天注射单剂量的CIS。给予CIS的小鼠血清血尿素氮（BUN）和肌酐升高，并且在肾脏中观察到多种组织病理学改变。CIS增加了小鼠肾脏中的丙二醛（MDA）、一氧化氮（NO）、核因子-κB（NF-κB）p65、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β，并降低了细胞抗氧化剂水平。TAX显著预防了肾脏损伤，改善了血清BUN和肌酐水平，以及肾脏MDA、NO、NF-κB p65和促炎细胞因子水平，并增强了给予CIS的小鼠的抗氧化防御能力。TAX下调了Bax和半胱天冬酶-3，并上调了Bcl-2。这些作用与给予CIS的小鼠中核因子红细胞2相关因子2（Nrf2）表达上调和血红素加氧酶（HO）-1活性上调有关。总之，TAX通过减轻组织损伤、氧化应激、炎症和细胞死亡，预防了CIS诱导的AKI。TAX的保护作用与Nrf2/HO-1信号通路的上调有关。
