Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression.

Background and Purpose: Nicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as a promising therapeutic approach to treat drug‐induced lung toxicity. This study aimed to explore the protective role of nicorandil in arsenic trioxide (ATO)‐induced lung injury and to elucidate the underlying mechanistic pathways. Experimental Approach: We assessed the effects of nicorandil (15 mg·kg−1, p.o.) in a rat model of pulmonary injury induced by ATO (5 mg·kg−1, i.p.). The assessment included oxidative stress biomarkers, inflammatory cytokine levels, and other biomarkers, including sirtuin‐1, sirtuin‐3, STAT3, TFAM, and JAK in lung tissue. Histological examination using H&E staining and molecular investigations using western blotting and PCR techniques were conducted. Key Results: In our model of lung injury, treatment with nicorandil ameliorated pathological changes as seen with H&E staining, reduced tissue levels of toxicity markers, and exerted significant antioxidant and anti‐inflammatory actions. On a molecular level, treatment with nicorandil down‐regulated JAK, STAT3, PPARγ, Nrf2, VEGF, p53, and micro‐RNA 132 while up‐regulating Sirt1, 3, TFAM, AMPK, and ERR‐α in lung tissue. Conclusions and Implications: The results presented here show nicorandil as a significant agent in attenuating lung injury induced by ATO in a rodent model. Nonetheless, further clinical studies are warranted to strengthen these findings. [ABSTRACT FROM AUTHOR]