Therapeutic Potential of <scp> <i>Carica papaya</i> </scp> (L.) Extract on <scp>NRF2</scp> / <scp>KEAP1</scp> and Apoptotic Pathways in Asbestos‐Induced Lung Toxicity

ABSTRACT Plant derived natural products and medicinal herbs have recently gain more attention as therapeutic agents to treat various ailments. The current study aims to explore the potential role of C. papaya 's natural intervention in reducing the asbestos‐induced pulmonary damage. A total of 32 male albino rats were grouped into NC, PC, STD (Montelukast Sodium 10 mg/kg), and C.P (500 mg/kg) groups, having eight animals in each group. Experimental units from the PC were exposed to asbestos fibers in a glass chamber for 2–3 h daily. Biological tissues for histopathology were preserved in formalin, lung tissue for qRT‐PCR was immersed in TRIzol, broncho‐alveolar lavage fluid (BALF) was collected for protein analysis, and serum was separated for oxidative biomarkers. Data was analyzed by the ANOVA and Tukey's test, and GraphPad Prism (v 8.0) was used for graphical representation. Results of the study revealed that after treatment, serum antioxidant markers were significantly enhanced in the C.P group (p ≤ 0.05) , whereas oxidative markers were reduced significantly in the C.P group (p ≤ 0.05) . Markers of protein analysis from BALF and wet‐to‐dry ratio increased in the PC group, but a significant decline was seen in the C.P group (p ≤ 0.05) . Results of qRT‐PCR showed upregulation of oxidative response pathway molecules and apoptotic markers in PC such as NRF1, DUOX, DUOXA1, DUOXA2, BAX, BID, CASP9, CYT‐C, and NFE‐2 L2. Parallel to this, an elevated response from antioxidant markers and calcium homeostasis regulators was seen in the C.P‐treated group. Microscopic insights revealed normal parenchyma of the lung and trachea in the NC group, which was worsened with thickened airways, fibrotic alveolar walls, and lodged fibers of asbestos seen in the tissue samples of the PC group. Treatment with C. papaya revealed a restored histopathological profile with better alveolar architecture and mitigated effects of asbestos fibers. The results of this study suggest that C. papaya exhibits strong antioxidant potential to mitigate oxidative stress caused by inorganic source.