Pirfenidone attenuates homocysteine‑induced apoptosis by regulating the connexin 43 pathway in H9C2 cells

Abstract

Pirfenidone (PFd) is an anti-fibrotic agent that is clinically used in the treatment of idiopathic pulmonary fibrosis. PFd has been shown to exert protective effects against damage to orbital fibroblasts, endothelial cells, liver cells and renal proximal tubular cells; however, its effect on myocardial cell apoptosis remains unclear. The present study aimed to characterize the effects of PFd on homocysteine (Hcy)-induced cardiomyocyte apoptosis and investigated the underlying mechanisms. H9c2 rat cardiomyocytes were pre-treated with PFd for 30 min followed by Hcy exposure for 24 h. The effects of PFd on cell cytotoxicity were evaluated by ccK-8 assay. The apoptosis rate of each group was determined by flow cytometry. The protein and mRNA levels of connexin 43 (cx43), Bax, B-cell lymphoma-2 (Bcl-2) and caspase-3 were measured by western blot analysis and reverse transcription-quantitative PcR, respectively. The present results demonstrated that the apoptotic rate increased following Hcy exposure, whereas the apoptotic rate significantly decreased following PFd pre-treatment. Furthermore, the ratio of Bax/Bcl2 was upregulated following Hcy exposure, and Hcy upregulated the expression levels of cleaved caspase-3 and cx43. Notably, these effects were prevented by PFd. Additionally, the effects of PFd were inhibited by the Cx43 agonist, AAP10. In summary, the findings of the present study demonstrate that PFd protects H9c2 rat cardiomyocytes against Hcy-induced apoptosis by modulating the cx43 signaling pathway.

Pirfenidone: A novel hypothetical treatment for COVID-19

“…It has been shown that Fas-dependent alveolar apoptosis that results in inflammatory reaction and finally interstitial fibrosis is responsible for the battle against viruses and also responsible for sequels of infections such as Poxvirus, bacterial LPS, etc [35,47]. On the other hand, it has been shown that pirfenidone could decrease apoptosis [19,[48][49][50][51].…”

Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model

“…Furthermore, an Hcy-induced myocardial cell apoptosis was established in vitro . This model is widely used to study cardiomyocyte apoptosis ( Zhang et al, 2017 ; Aminzadeh & Mehrzadi, 2018 ; Chen et al, 2020 ).…”

Commentary: Antifibrotics in COVID-19 Lung Disease: Let Us Stay Focused

“…The antioxidant character of Pirfenidone suggests its capability for the treatment of hyperimmune response ( 3 , 24 ). Pirfenidone could decrease apoptosis and as a result combat sever viral inflammation, ARDS, and ARDS fibrosis ( 25 , 26 ). Finally, it has been demonstrated that Pirfenidone inhibits the AT1R/p38 MAPK pathway, decreases angiotensin II, and angiotensin II type 1 receptor, as well as angiotensin-converting enzyme (ACE) expression, which will both protect cells from developing fibrosis (LXR-α), and limit entrance of the COVID-19-SARS virus into cells by decreasing ACE receptors ( 2 , 27 , 28 ).…”