Protective Effects of Carvacrol on Mercuric Chloride-Induced Lung Toxicity Through Modulating Oxidative Stress, Apoptosis, Inflammation, and Autophagy

Abstract

Mercuric chloride (HgCl₂) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl₂ can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl₂. Intraperitoneal injections of HgCl₂ at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl₂-induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1β, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl₂, the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl₂-induced autophagy damage. After HgCl₂ treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl₂-induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.

Keywords: apoptosis; carvacrol; inflammation; lung toxicity; mercuric chloride; oxidative stress.