Carvacrol Reduces Mercuric Chloride-Induced Testicular Toxicity by Regulating Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Histopathological Changes.

Abstract

Mercuric chloride (HgCl₂) is a heavy metal that is toxic to the human body. Carvacrol (CAR) is a flavonoid found naturally in plants and has many biological and pharmacological activities including anti-inflammatory, antioxidant, and anticancer activities. This study aimed to investigate the efficacy of CAR in HgCl₂-induced testicular tissue damage. HgCl₂ was administered intraperitoneally at a dose of 1.23 mg/kg body weight alone or in combination with orally administered CAR (25 mg/kg and 50 mg/kg body weight) for 7 days. Biochemical and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and autophagy pathways in testicular tissue. CAR treatment increased HgCl₂-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels. In addition, CAR reduced MDA levels, a marker of lipid peroxidation. CAR decreased the levels of inflammatory mediators NF-κB, TNF-α, IL-1β, COX-2, iNOS, MAPK14, MAPK15, and JNK. The increases in apoptotic Bax and Caspase-3 with HgCl₂ exposure decreased with CAR, while the decreased antiapoptotic Bcl-2 level increased. CAR reduced HgCl₂-induced autophagy damage by increasing Beclin-1, LC3A, and LC3B levels. Overall, the data from this study suggested that testicular tissue damage associated with HgCl₂ toxicity can be mitigated by CAR administration.