Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: Linalool could protect against cisplatin-induced kidney function and tissue damage.
Highlights
Linalool, a naturally occurring acyclic monoterpene alcohol, is found in numerous aromatic plant families such as Lamiaceae and Rutaceae
The cisplatin-administered group had the highest number of animal deaths, while no animal death was recorded in the control or in the linalool pre-treated groups
Pre-treatment with linalool at doses of 50 and 100 mg/kg revealed a significant renal protection effect as demonstrated by the reduction in renal function Blood urea nitrogen (BUN) and creatinine compared with cisplatin administered animals
Summary
A naturally occurring acyclic monoterpene alcohol, is found in numerous aromatic plant families such as Lamiaceae and Rutaceae. It is a constituent of numerous essential oils produced by many common and edible plants such as peppermint, coriander, and cinnamon [1]. The second enantiomer is (R)-(−)-linalool, called licareol, which possesses a lavender-like odor [2,3]. The monoterpene linalool is a well-known essential oil component produced by several aromatic plants. Results: Linalool ameliorated kidney function after cisplatin challenge and managed all oxidation system parameters including GSH, SOD, CAT, MDA, NADPH, and the
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