Curcumin Protects against Arsenic and Cadmium-Induced Lung Toxicity in Rats by Modulating Bax/Bcl-2/caspase-3 Pathway: In Vivo and In Silico Approaches

Abstract

The present study aims to investigate the putative protective role of curcumin (CUR) against oxidative stress and lung damage caused by a heavy metal mixture (Cd+As) with cadmium (Cd) + arsenic (As). Wistar albino rats were randomly divided into five experimental groups: Control, 0.44 + 5.55 mg/kg Cd+As, 100 mg/kg CUR, 100 CUR + Cd+As, and 200 CUR + Cd+As groups. The Cd+As increased malondialdehyde levels and oxidative stress. However, it also led to a decrease in levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) in lung tissue homogenates. Different doses of CUR effectively prevented Cd+As-induced lipid peroxidation and suppression of antioxidant capacity in lung tissue. Also, lung tissue administered Cd+As showed elevated levels of congestion, inflammation, alveolar damage, and apoptosis, as evidenced by decreased Bcl-2 and increased expression levels of Bax and caspase-3. The high dose remarkably improved lung injury in Cd+As-injected rats, better than the low dose. The results show that CUR treatment is effective in protecting against Cd+As-induced lipid peroxidation and reducing the negative effects of metal mixture on antioxidant status. This study suggests that CUR may be a potential new approach for the prevention/treatment of Cd+As-induced pulmonary toxicity and possibly other lung diseases associated with oxidative stress and inflammation. Furthermore, in silico studies on how CUR and Cd+As treatments affect the activities of the enzymes CAT and GPx1 showed that ROS induced by Cd+As treatment caused changes in the enzymes CAT and GPx1, while CAT was modulated by CUR treatment, whereas GPx1 was not modulated. © 2026 Wiley Periodicals LLC.