Study of the effects of the hybrid naproxen hydrogen sulfide (H2S) donor (ATB-346) on the proliferation and migration of vascular smooth muscle cells in culture.

• Grant number: 25/22757-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Nicolas Muscara
• Grantee: Felipe Bedin Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 25/13877-5 - Study of the effects of the hybrid naproxen hydrogen sulfide (H2S) donor (ATB-346) on the proliferation and migration of vascular smooth muscle cells in culture., AP.R

Abstract

Inflammation is the physiological response of the host organism triggered by infectious agents, tissue lesions or other noxious stimuli. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used agents for treatment of acute and chronic inflammatory processes. However, gastrointestinal lesions are one of the main adverse effects reported, leading to discomforts and the consequent reduction of adherence to the treatment. In this way, new therapeutic approaches reducing such adverse effects are welcome, as those based on the anti-inflammatory and antioxidant proprieties of hydrogen sulfide (H2S). The vascular and angiogenic effects of H2S are underscored among its physiological functions. Furthermore, the antioxidant, anti-inflammatory and bioenergetic effects evoke the relevant and wide potential of H2S donors as therapeutic tools. In this way, the newly developed NSAIDs derivatives coupled to H2S donors (e.g., tiobenzamide; TBZ) are underscored. Compound ATB-346 (otenaproxesul), a naproxen (NAP) derivative obtained by esterification with 4-hydroxy TBZ, shows more potent anti-inflammatory effects than those of NAP, as well as reduced incidence of gastrointestinal lesions. However, no evidence linking the mentioned mechanisms of protection with angiogenesis were so far reported. Thus, the objective of this project is to investigate the effects of ATB-346 on the proliferation of vascular smooth muscle cells derived from rat aorta (A7r5) in culture. Cell viability will be assessed using the MTT reduction assay, and cytolytic effects will be evaluated by measuring lactate dehydrogenase (LDH) activity in the culture supernatants. Cell proliferation will be analyzed through total protein staining using sulforhodamine B (SRB) and by the scratch wound healing assay. Data will be expressed as mean ± standard error of the mean, and a significance level of 5% will be considered. (AU)