Carveol ameliorates mercury-induced oxidative stress, neuroinflammation, and neurodegeneration in a mouse brain.

Abstract

BACKGROUND:

Mercury compounds are the world's third most hazardous substance. Mercury (II) chloride, also known as mercuric chloride (HgCl2), has been shown to have neurotoxic properties in a variety of forms. In numerous investigations, oxidative stress has been established as a key contributor to HgCl2-induced neurotoxicity. Carveol has been researched as an antioxidant and Nrf2-activator in several studies. This study was conducted to investigate if the carveol could protect mice against HgCl2-induced neuronal damage.

METHODS:

Mice were exposed to a dose of 0.4 mg/kg of HgCl2 and 20 mg/kg of carveol for 21 days. Animals were then subjected to behavioral evaluation through various methods such as open field test (OFT), elevated plus maze test (EPM), morris-water maze test (MWM), and Y-maze test.

RESULTS:

Results indicated hippocampal-related behavior anomalies which were improved significantly after carveol treatment. Oxidative stress was accompanied by excessive neuroinflammation, which was demonstrated by elevated levels of inflammatory markers such as TNF-α, p-NFkB, and COX-2, and were measured by Western blot, ELISA, and immunohistochemistry. These elevated levels of inflammatory markers were significantly mitigated upon treatment with carveol. To further investigate the participation of the JNK pathway, we used SP-600125 to inhibit JNK, which enhanced the neuroprotective effects of carveol. Moreover, molecular docking and modeling studies were used to validate these effects.

CONCLUSION:

Our findings indicate that carveol can inhibit the p-JNK pathway, thereby inhibiting HgCl2-induced apoptosis and downregulating the expression of inflammatory mediators.

• Authors: Abdullah Alattar, Arooj Mohsin Alvi, Sajid Rashid, Nadia Hussain, Mehreen Gul, Muhammad Ikram, Atif Ali Khan Khalil, Reem Alshaman, Fawad Ali Shah, Shupeng Li, Jingbo Li
• Journal: Neurotoxicology (Neurotoxicology) Vol. 92 Pg. 212-226 (09 2022) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 35963490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Chlorides
• Cyclohexane Monoterpenes
• Hazardous Substances
• Inflammation Mediators
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• Mercuric Chloride
• carveol
• Cyclooxygenase 2
• Mercury

Topics

• Animals
• Antioxidants (pharmacology)
• Brain (metabolism)
• Chlorides
• Cyclohexane Monoterpenes
• Cyclooxygenase 2 (metabolism)
• Hazardous Substances (pharmacology)
• Inflammation Mediators (metabolism)
• Mercuric Chloride (toxicity)
• Mercury
• Mice
• Molecular Docking Simulation
• NF-E2-Related Factor 2 (metabolism)
• Neuroinflammatory Diseases
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (drug therapy)
• Oxidative Stress
• Tumor Necrosis Factor-alpha (metabolism)