Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt; Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Germany; Department of Endocrinology, Diabetes and Nutrition at the Center for Cardiovascular Research (CCR), Charité-University Medicine Berlin, Germany.
Department of Biology, Faculty of Science, Jouf University, Saudi Arabia.
Biomed Pharmacother. 2018 Oct;106:499-509. doi: 10.1016/j.biopha.2018.06.171. Epub 2018 Jul 11.
Commiphora molmol possesses multiple therapeutic benefits against various diseases; however, its protective role against methotrexate (MTX) renal toxicity has not been previously investigated. MTX is a dihydrofolate reductase inhibitor that can induce acute kidney injury (AKI). This study evaluated the in vitro antioxidant activity and the protective effect of C. molmol resin extract against MTX-induced oxidative stress, inflammation and renal injury. Male Wistar rats received 125 and 250 mg/kg C. molmol resin extract for 15 days and a single injection of MTX at day 16. C. molmol showed a radical scavenging activity against DPPH, superoxide and nitric oxide (NO) radicals. Rats received MTX showed renal injury evidenced by the significantly elevated serum creatinine and urea, and the histological alterations. The kidney of MTX-induced rats exhibited increased lipid peroxidation, NO, NF-κB and pro-inflammatory cytokines. Pre-treatment with C. molmol prevented MTX-induced kidney injury and attenuated oxidative stress and inflammation. C. molmol down-regulated Bax and enhanced the activity and expression of the antioxidant defenses. Furthermore, the expression of Bcl-2, Nrf2, NQO-1 and HO-1 was down-regulated in the kidney of MTX-induced rats. Pre-treatment with C. molmol resin up-regulated Bcl-2 and activated Nrf2/HO-1 signaling in the kidney of MTX-induced rats. In conclusion, C. molmol resin provided protection against MTX-induced AKI via activation of Nrf2 signaling and mitigation of oxidative stress.
没药具有多种治疗益处，可用于治疗多种疾病；然而，其对抗甲氨蝶呤（MTX）肾毒性的保护作用尚未被研究过。MTX 是一种二氢叶酸还原酶抑制剂，可导致急性肾损伤（AKI）。本研究评估了没药树脂提取物的体外抗氧化活性及其对 MTX 诱导的氧化应激、炎症和肾损伤的保护作用。雄性 Wistar 大鼠接受 125 和 250mg/kg 没药树脂提取物治疗 15 天，并在第 16 天接受单次 MTX 注射。没药显示出对 DPPH、超氧自由基和一氧化氮（NO）自由基的清除活性。接受 MTX 的大鼠表现出肾损伤，血清肌酐和尿素显著升高，组织学改变。MTX 诱导的大鼠肾脏表现出脂质过氧化、NO、NF-κB 和促炎细胞因子增加。用没药预处理可预防 MTX 诱导的肾损伤，并减轻氧化应激和炎症。没药下调 Bax 并增强抗氧化防御的活性和表达。此外，MTX 诱导的大鼠肾脏中 Bcl-2、Nrf2、NQO-1 和 HO-1 的表达下调。用没药树脂预处理可上调 Bcl-2 并激活 MTX 诱导的大鼠肾脏中的 Nrf2/HO-1 信号通路。总之，没药树脂通过激活 Nrf2 信号通路和减轻氧化应激，为 MTX 诱导的 AKI 提供了保护。
