H 2 S Prodrug, SG-1002, Protects against Myocardial Oxidative Damage and Hypertrophy In Vitro via Induction of Cystathionine β-Synthase and Antioxidant Proteins

• Published in: Biomedicines 2023-02, Vol.11 (2)
• Main Authors: Islam, Rahib K, Donnelly, Erinn, Donnarumma, Erminia, Hossain, Fokhrul, Gardner, Jason D, Islam, Kazi N
• Format: Article
• Language: English
• ISSN: 2227-9059; 2227-9059

Endogenously produced hydrogen sulfide (H S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H O increased the levels of H S, H S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative stress. SG-1002 also decreased the expression of hypertrophic/HF protein markers such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), galectin-3, TIMP1, collagen type III, and TGF-β1 in stressed HL-1 cells. Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with H O . Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing H S levels or H S producing enzymes, CBS, and antioxidant proteins.