Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats

Abstract

Background: D-carvone is a monoterpene that exists in the essential oils of several plant species. Hepatic ischemia-reperfusion (Hep I/R) takes place clinically during different scenarios of liver pathologies. The aim of the current investigation is to disclose the hepato-protective actions of carvone against Hep I/R-induced damage and to reveal the underlying mechanism. Material and methods: Rats were assigned into five groups: sham and carvone plus sham groups, in which rats were administered either saline or carvone orally for three weeks prior to the induction of Hep I/R. In the Hep I/R group, rats were administered saline orally prior to the Hep I/R induction operation. The carvone 25 plus Hep I/R and Carvone 50 plus Hep I/R groups were administered carvone (25 and 50 mg/kg, respectively) for three weeks, followed by the induction of Hep I/R. Results: Liver ischemic animals demonstrated impaired liver function, several histopathological variations, and reduced levels of antioxidant enzyme activities. Furthermore, the Hep I/R groups showed the elevated gene expression of high-mobility group box 1 (HMGB1), toll-like receptors 4 (TLR4), nuclear factor kappa B (NFκB), and LR family pyrin domain containing 3 (NLP3), with subsequent escalated adhesion molecule 1 (ICAM-1), neutrophil infiltration, and several inflammatory mediators, including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), as well as apoptotic markers. Pretreatment with D-carvone alleviated ischemia/reperfusion-induced impaired liver function, diminished the histopathological deviations, and augmented the antioxidant enzymes. In addition, D-carvone mitigated the gene expression of HMGB1, TLR4, NFκB, and NLP3, with a subsequent reduction in ICAM-1, neutrophils infiltration, inflammatory mediators, and apoptotic markers. Conclusion: Rats pretreated with D-carvone exhibited hepato-protective actions against Hep I/R-induced damage via the downregulation of HMGB1, TLR4, NFκB, NLP3, associated inflammatory mediators, and apoptotic markers.

Molecular Characterization of High Mobility Group Box 1a (HMGB1a) Gene in Red‐Bellied Pacu, Piaractus brachypomus

“…Pathogenic stimulation and oxidative stress induce the nucleocytoplasmic translocation of HMGB1 [ 4 ], which in grass carp induces heat shock protein 70 (HSP70) to move to the nucleus where it interacts with HMGB1b generating the nucleocytoplasmic translocation of the protein and activation of the HMGB1b-Beclin 1-mediated autophagy [ 4 ]. However, outside the cell, HMGB1 is a linker of innate and acquired immunity, as it acts as a cytokine [ 1 , 5 ], through interaction with pattern recognition receptors such as TLR and RAGE [ 4 , 11 ], leading to activation of the primary myeloid differentiation response 88 protein (MyD88) dependent on the NF-kB pathway [ 36 ]. In addition, it plays a role in apoptosis, cell migration, and cytoskeleton reorganization [ 1 ].…”

Plant Monoterpenes and Essential Oils as Potential Anti-Ageing Agents: Insights from Preclinical Data

“…↓ Serum and brain IL-1β and TNF-α levels; ↓ IL-6 and IL-4 levels; ↑ IL-10 levels; ↓ NLRP3, ASC, TLR4, IL-1β, TNF-α mRNA levels [142] Hepatic I/R-induced injury rat model (25 and 50 mg/Kg, gavage; 3 weeks before I/R) ↓ HMGB1, TLR4, NF-κB and NLRP3 mRNA expression; ↓ TLR4 and NF-κB immunoreactivity; ↓ ICAM-1, MPO, IL-1β, IL-6 and TNF-α protein levels; ↑ IL-10 protein levels [143] 1,8-Cineole SAH-induced early brain injury rat model (100 mg/Kg, i.p. ; 1 h before SAH and 30 min after)…”