Carvacrol mitigates Mercury chloride induced neurotoxicity by regulation of NRF-2/HO-1/NF-κB expression

Mercury chloride (HgCl2) is an environmental pollutant that has serious toxic effects on the central nervous system. Carvacrol (CRV), which has phytotherapeutic, pharmacological, biological, and aromatic properties, has neuroprotective effects. The aim of this study was to investigate the possible neuroprotective effect of CRV on HgCl2-induced central neurotoxicity in rats. In the study, HgCl2 (1.23 mg/kg) and CRV (25 or 50 mg/kg) alone or their combinations were administered to rats for 7 days. Then, the proteins and pathological changes specific to autophagy, apoptosis, inflammation and oxidative stress processes in the brain tissue were analyzed by biochemical, molecular, histological and immunohistochemical methods. It was determined that CRV treatment significantly increased antioxidant enzyme (catalase, superoxide dismutase and glutathione peroxidase) activities and non-enzymatic (glutathione) antioxidants while reducing HgCl2-induced lipid peroxidation. In addition, it was determined that Nrf-2, HO-1, NQO1 mRNA transcript levels, which are among the oxidative stress parameters of CRV administration, increased. It was observed that HgCl2 increased the expression of NF-kappa B, TNF-alpha, IL-1 beta, iNOS and nNOS cytokines and Rage, STAT3, NLRP3, MAPK14, MAPK15 and JNK, whereas CRV treatment suppressed these genes. In this study, it was determined that HgCl2 induces apoptotic (caspase-3, Bax, Bcl-2) and autophagic (Beclin-1) markers, whereas CRV can protect brain tissues from the destructive effect of H HgCl2 by showing anti-apoptotic and antiautophagic. In addition, decreased Akt-2 and Foxo1 expression and increased GFAP levels in HgCl2-induced brain tissue were regulated after CRV administration. The H&E staining results showed that CRV preserved the histological architecture and integrity of the cerebral cortex. The findings of this study indicate that CRV has neuropreventive potential against HgCl2-induced neurotoxicity by reducing oxidative stress, inflammation, apoptosis and autophagy.

Journal

JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY

Year

2025

Volume

91

ISSN

0946-672X

eISSN

1878-3252

DOI

10.1016/j.jtemb.2025.127715

WoS UID

WOS:001584476200002