Sodium chromate induces acute lung injury via mitogen-activated protein kinase–mediated oxidative stress and inflammation

Abstract

Sodium chromate (Na₂CrO₄), commonly used in industrial processes, poses significant health hazards due to its well-documented pulmonary toxicity. Despite its known environmental impact, the molecular mechanisms underlying Na₂CrO₄-induced acute lung injury (ALI) remain poorly understood. This study investigates the role of oxidative stress and key inflammatory pathways in Na₂CrO₄-induced pulmonary toxicity both in vivo and in vitro. In vivo C57BL/6 mice were intratracheally exposed to varying doses of Na₂CrO₄ (1–25 mg/kg) to assess lung inflammation, oxidative stress, and tissue damage. Histological analysis, bronchoalveolar lavage fluid (BALF) collection, and enzyme-linked immunosorbent assay (ELISA) were performed to quantify immune cell infiltration and cytokine production (IL-6 and TNF-α). In vitro, MLE-12 alveolar epithelial cells were treated with Na₂CrO₄ to evaluate cytotoxicity, apoptosis, and oxidative stress using MTT, Annexin V/PI staining, and DCF-DA assays. The involvement of NF-κB and MAPK pathways was analyzed via Western blotting, with pathway-specific inhibitors applied to dissect their roles. Na₂CrO₄ exposure induced acute lung inflammation characterized by neutrophil infiltration, increased lung weight-to-body weight ratio, and elevated IL-6 and TNF-α levels. Significant oxidative stress was observed, while NF-κB activation was limited, and robust activation of the MAPK signaling pathway was detected. Pharmacological inhibition of these pathways significantly mitigated Na₂CrO₄-induced pulmonary toxicity. This study highlights oxidative stress and MAPK pathway activation as central mechanisms in Na₂CrO₄-induced pulmonary toxicity. The findings underscore the potential of targeting MAPK signaling to mitigate heavy metal-induced lung injury and emphasize the public health risks associated with environmental Na₂CrO₄ exposure.