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.
Biomolecules. 2020 Oct 28;10(11):1488. doi: 10.3390/biom10111488.
The monoterpene linalool is a well-known essential oil component produced by several aromatic plants. Cisplatin is a widely used anticancer drug that produces many side effects, particularly nephrotoxicity. Here, we aimed to inspect linalool's protective activity against cisplatin-induced nephrotoxicity and explore part of the underlying mechanisms.
Male Wistar rats were given linalool (50 and 100 mg/kg/day orally) for 15 days; then challenged with cisplatin (8 mg/kg) on the 12th day. Renal function parameters, oxidative stress, inflammatory and apoptotic markers, and toll-like receptor pathway gene, and protein expressions were investigated. Histopathology, immunohistochemistry, and cell-line mediated cytotoxicity assays were conducted.
Linalool ameliorated kidney function after cisplatin challenge and managed all oxidation system parameters including GSH, SOD, CAT, MDA, NADPH, and particularly the Nrf2-mediated pathway markers. Linalool decreased TLR4, MYD88 and TRIF gene and protein expressions; diminished related inflammatory mediators such as TNF-α, IL-1β, IL-6, and NF-κB; and down-regulated HMBG1. Linalool mitigated cisplatin-induced apoptotic markers such as caspase 3, caspase 9, and Bax expression, and boosted the anti-apoptotic Bcl2 expression. Linalool potentiated the cytotoxic effect of cisplatin when investigated on HeLa and PC3 human cancer cell lines.
Linalool could protect against cisplatin-induced kidney function and tissue damage.
单萜醇芳樟醇是几种芳香植物产生的一种众所周知的精油成分。顺铂是一种广泛使用的抗癌药物，会产生许多副作用，特别是肾毒性。在这里，我们旨在检查芳樟醇对顺铂诱导的肾毒性的保护活性，并探讨部分潜在机制。
雄性 Wistar 大鼠连续 15 天每天口服给予芳樟醇（50 和 100mg/kg）；然后在第 12 天用顺铂（8mg/kg）进行挑战。研究了肾功能参数、氧化应激、炎症和凋亡标志物以及 Toll 样受体途径基因和蛋白表达。进行了组织病理学、免疫组织化学和细胞系介导的细胞毒性测定。
芳樟醇改善了顺铂挑战后的肾功能，并调节了所有氧化系统参数，包括 GSH、SOD、CAT、MDA、NADPH，特别是 Nrf2 介导的途径标志物。芳樟醇降低了 TLR4、MYD88 和 TRIF 基因和蛋白表达；减少了相关炎症介质，如 TNF-α、IL-1β、IL-6 和 NF-κB；并下调了 HMBG1。芳樟醇减轻了顺铂诱导的凋亡标志物，如 caspase 3、caspase 9 和 Bax 的表达，并增强了抗凋亡 Bcl2 的表达。当在 HeLa 和 PC3 人癌细胞系上进行研究时，芳樟醇增强了顺铂的细胞毒性作用。
芳樟醇可以预防顺铂引起的肾功能和组织损伤。
