Abstract
- OBJECTIVE: Hepatic isch-emia-reperfusion (H I/R) injury is a frequent clin-ical event during which the leading contributing players are inflammation and oxidative stress responses. 0-caryophyllene (BCP), a natural bicyclic sesquiterpene, is an essential oil com-ponent of different plant species and edibles. This study aims to identify whether BCP pre-treatment could avert H I/R injury with inspec-tions of the underlying mechanisms. MATERIALS AND METHODS: Animals were devised into five groups; Sham and BCP + Sham; the animals were administered saline or BCP (200 mg/kg, orally) respectively; H I/R group, the animals were administered saline orally for 14 days before induction of H I/R; BCP100 and BCP200, the animals were administered BCP (100 and 200 mg/kg, respectively) for 14 days, followed by induction of H I/R.RESULTS: H I/R showed markedly increased ALT, AST, MDA, and lowered antioxidant enzyme activities, while the Nrf2/HO1/NQO1 pathway components were significantly augmented. The TLR4/NF-Kappa B/NLRP3 elements were deterred, and subsequently, escalations in the inflamma-tory mediators (IL-10, IL-6, and TNF-alpha), adhesion molecule ICAM-1, neutrophils infiltration (MPO), and apoptotic markers were observed. Pretreat-ment with BCP amplified the antioxidant enzyme activities and Keap1/Nrf2/HO1/NQO1 pathway components. BCP pretreatment lowered TLR4/ NF-Kappa B/NLRP3 pathway elements, which mitigat-ed inflammatory mediators, ICAM-1, MPO, and apoptotic markers. CONCLUSIONS: The protective effect of BCP against hepatic I/R induced injury might be ac-complished via mitigation of oxidative stress by regulating the Keap1/Nrf2/HO1/NQO1 pathway and inhibition of the inflammatory process viamanipulating the TLR4/ NF-Kappa B/ NLRP3, reflect-ed by inflammatory markers, neutrophils recruit-ment, and adhesion molecules reduction. BCP might be a potential therapeutic agent for allevi-ating hepatic I/R-induced injury.