Nicorandil mitigates amiodarone‐induced pulmonary toxicity and fibrosis in association with the inhibition of lung TGF‐β1/PI3K/Akt1‐p/mTOR axis in rats.

Autor: Harb, Inas, Ashour, Hend, Rashed, Laila A., Mostafa, Abeer, Samir, Mai, Aboulhoda, Basma Emad, El‐hanbuli, Hala, Rashwan, Eman, Mahmoud, Heba
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Zdroj: Clinical & Experimental Pharmacology & Physiology; Jan2023, Vol. 50 Issue 1, p96-106, 11p, 1 Color Photograph, 1 Chart, 4 Graphs
Abstrakt: The long‐term side effect of the antiarrhythmic drug, amiodarone (AMIO), such as lung toxicity, remains a critical clinical issue. The previous knowledge denotes diverse antioxidant, anti‐inflammatory, and antifibrotic properties of the anti‐anginal drug, nicorandil (NI). Therefore, we aimed to investigate the possible protective effect of NI on pulmonary tissue remodelling following AMIO‐induced lung toxicity. The included rats were assigned into four equal groups (n = 8): (1) control, (2) control group that received NI 10 mg kg−1 day−1, (3) model group that received AMIO in a dose of 60 mg kg−1 day−1, and (4) treated group (AMIO‐NI) that were treated with AMIO plus NI as shown above. Drug administration continued for 10 weeks. AMIO resulted in deteriorated (p < 0.001) pulmonary functions accompanied by respiratory acidosis. AMIO showed an obvious histological injury score with intense collagen deposition, disturbed nitric oxide synthase enzymes (NOS/iNOS), and increased alpha smooth muscle actin expression. Furthermore, AMIO upregulated the transforming growth factor (TGF‐β1)/phosphoinositide‐3 kinase (PI3K)‐Akt1‐p/mammalian target of rapamycin (mTOR) axis, which determined the possible mechanism of AMIO on pulmonary remodelling. NI treatment significantly (p < 0.001) prevented the AMIO‐induced lung toxicity, as well as inhibited the TGF‐β1/PI3K/Akt1‐p/mTOR axis in the lung tissue of rats. The results were confirmed by an in‐vitro study. Conclusion: The current results revealed that NI was effective in preserving the lung structure and functions. Amelioration of the oxidative stress and modulation of TGF‐β1/PI3K/Akt1‐p/mTOR have been achieved. This study suggests NI administration as a preventive therapy from the serious pulmonary fibrosis side effect of AMIO. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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