Protective effect of linalool against morphine-induced renal injury: Modulation of oxidative stress and PI۳K/AKT/L-FABP signaling pathway

Objective(s): Opioid misuse and prolonged therapeutic use are increasingly linked to systemic toxicities, including renal dysfunction. Morphine has been shown to induce oxidative stress and disrupt intracellular signaling pathways implicated in kidney injury. Linalool, a naturally occurring monoterpene with antioxidant and anti-inflammatory properties, may protect against drug-induced nephrotoxicity. This study investigated the protective effects of linalool against morphine-induced renal injury in rats, focusing on oxidative stress parameters and modulation of the PI۳K/AKT/L-FABP signaling pathway.Materials and Methods: Thirty-two male Wistar rats were randomly allocated into four groups (n = ۸/group): Control, Morphine (۱۰ mg/kg, SC), Linalool (۵۰ mg/kg, IP), and Morphine + Linalool. Treatments were administered for three consecutive days using a conditioned place preference protocol to model morphine exposure. Renal function markers, oxidative stress parameters (MDA, SOD, CAT), histopathological alterations, and renal expression of AKT, PI۳K, and L-FABP proteins were evaluated.Results: Morphine administration significantly elevated serum creatinine, urinary injury markers, and lipid peroxidation (MDA), while decreasing antioxidant enzyme activities (SOD and CAT). Morphine also down-regulated AKT expression and PI۳K, and up-regulated FABP in renal tissue. Co-treatment with linalool significantly improved biochemical parameters, attenuated histopathological damage, reduced oxidative stress, suppressed FABP overexpression, and restored AKT and PI۳K expression.Conclusion: Linalool exerts renoprotective effects against morphine-induced injury by reducing oxidative stress and modulating PI۳K/AKT/L-FABP signaling. These findings suggest that linalool has therapeutic potential for preventing opioid-associated renal dysfunction.

کلیدواژه ها:

Acute kidney injury ، L-FABP ، Linalool ، Morphine ، Oxidative stress ، PI۳K/Akt