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

被引:5
作者
Abdel-Wahab, Basel A. [1 ]
Zafaar, Dalia [2 ]
Habeeb, Mohammed Shafiuddin [1 ]
El-Shoura, Ehab A. M. [3 ]
机构
[1] Najran Univ, Coll Pharm, Dept Pharmacol, Najran, Saudi Arabia
[2] Modern Univ Technol & Informat, Dept Pharmacol & Toxicol, Fac Pharm, Cairo, Egypt
[3] Al Azhar Univ, Fac Pharm, Dept Clin Pharm, Assiut Branch, Assiut 71524, Egypt
关键词
AMPK/SIRT1/PGC-1; alpha/TFAM; JAK1/STAT3; pathway; arsenic trioxide; miRNA-132; nicorandil; oxidative stress; pulmonary injury; CONCISE GUIDE; ANTIOXIDANT; MACROPHAGES; PROTECTS; TISSUES; NRF2;
D O I
10.1111/bph.16414
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and PurposeNicorandil, 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 ApproachWe assessed the effects of nicorandil (15 mg<middle dot>kg-1, p.o.) in a rat model of pulmonary injury induced by ATO (5 mg<middle dot>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 ResultsIn 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, PPAR gamma, Nrf2, VEGF, p53, and micro-RNA 132 while up-regulating Sirt1, 3, TFAM, AMPK, and ERR-alpha in lung tissue.Conclusions and ImplicationsThe 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. image
引用
收藏
页码:3215 / 3231
页数:17
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