Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Curr Issues Mol Biol. 2021 Oct 24;43(3):1741-1755. doi: 10.3390/cimb43030123.
Geraniol, a natural monoterpene, is an essential oil component of many plants. Methotrexate is an anti-metabolite drug, used for cancer and autoimmune conditions; however, clinical uses of methotrexate are limited by its concomitant renal injury. This study investigated the efficacy of geraniol to prevent methotrexate-induced acute kidney injury and via scrutinizing the Keap1/Nrf2/HO-1, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 and -9 pathways.
Male Wister rats were allocated into five groups: control, geraniol (orally), methotrexate (IP), methotrexate and geraniol (100 and 200 mg/kg).
Geraniol effectively reduced the serum levels of creatinine, urea and Kim-1 with an increase in the serum level of albumin when compared to the methotrexate-treated group. Geraniol reduced Keap1, escalated Nrf2 and HO-1, enhanced the antioxidant parameters GSH, SOD, CAT and GSHPx and reduced MDA and NO. Geraniol decreased renal P38 MAPK and NF-κB and ameliorated the inflammatory mediators TNF-α, IL-1β, IL-6 and IL-10. Geraniol negatively regulated the apoptotic mediators Bax and caspase-3 and -9 and increased Bcl2. All the biochemical findings were supported by the alleviation of histopathological changes in kidney tissues.
The current findings support that co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury.
香叶醇是一种天然单萜，是许多植物精油的成分。甲氨蝶呤是一种抗代谢药物，用于癌症和自身免疫性疾病；然而，由于其伴随的肾损伤，甲氨蝶呤的临床应用受到限制。本研究通过研究 Keap1/Nrf2/HO-1、P38MAPK/NF-κB 和 Bax/Bcl2/caspase-3 和 -9 通路，研究了香叶醇预防甲氨蝶呤诱导的急性肾损伤的疗效。
雄性 Wistar 大鼠被分为五组：对照组、香叶醇（口服）、甲氨蝶呤（IP）、甲氨蝶呤和香叶醇（100 和 200mg/kg）。
与甲氨蝶呤治疗组相比，香叶醇有效降低了血清肌酐、尿素和 Kim-1 水平，增加了血清白蛋白水平。香叶醇降低了 Keap1，增加了 Nrf2 和 HO-1，增强了抗氧化参数 GSH、SOD、CAT 和 GSHPx，降低了 MDA 和 NO。香叶醇降低了肾 P38MAPK 和 NF-κB，并改善了 TNF-α、IL-1β、IL-6 和 IL-10 等炎症介质。香叶醇负调控凋亡介质 Bax 和 caspase-3 和 -9，并增加了 Bcl2。所有生化发现都得到了肾组织病理变化缓解的支持。
目前的研究结果支持香叶醇与甲氨蝶呤联合使用可能减轻甲氨蝶呤诱导的急性肾损伤。
