Hepatoprotective effects of linalool against liver ischemia-reperfusion: the role of Nrf2/HO-1/NQO1 and TLR4/RAGE/NFκB pathways.

Objective: Hepatic ischemia-reperfusion (H I/R) injury arises due to a temporary obstruction followed by the re-establishment of blood supply to the liver. Linalool (LIN), a main volatile constituent of essential oils in numerous aromatic plant species, exhibited various medicinal and pharmacological actions. This study investigated the protective effect of LIN on the status of H I/R, with the study of the possible mechanisms. In addition, linalool's antagonistic effects were tested against several metabolic targets using in silico molecular docking technique.

Materials And Methods: Wistar rats were allocated into five groups. Sham and LIN + Sham groups in which animals were administered either vehicle (1% CMC) or LIN (200 mg/kg/day) orally for two weeks. H I/R group in which rats were administered 1% CMC for two weeks and then experienced hepatic ischemia for 60 min followed by 6 hours of reperfusion. LIN 100 + H I/R and LIN 200 + H I/R groups in which rats were pretreated with LIN (100, 200 mg/kg/day) respectively for two weeks, then subjected to H I/R.

Results: H I/R-induced injury resulted in impaired liver function and activated Keap1/Nrf2/HO-1/NQO1 and HMGB1/TLR4/RAGE/NFкB pathways with subsequent oxidative stress, inflammation, and apoptosis. LIN pretreatment alleviated I/R-induced impairment in liver function, promoted Keap1/Nrf2/HO-1/NQO1, and mitigated the HMGB1/TLR4/RAGE/NFкB pathway. LIN pre-administration deterred adhesion molecule, neutrophils infiltration, RAGE, IL-1β, IL-6, TNF-α, and apoptosis.

Conclusions: LIN demonstrated hepato-protective effects against H I/R via instigation Keap1/Nrf2/HO-1/NQO1 and mitigating the HMGB1/TLR4/RAGE/NFкB pathways with subsequent deterring oxidative stress, inflammation, and apoptosis.