EFFECTS OF THE ADRENERGIC BLOCKERS TAMSULOSIN AND CARVEDILOL ON THE HOMEOSTASIS OF THE ENDOPLASMIC RETICULUM OF LIVER CELLS

Juan Carlos Rivera-Navarro, Mariana Yazmin Medina Pizaño, Sandra Luz Martínez-Hernández, Javier Ventura-Juárez, David Ibarra-Martínez and Martín Humberto Muñoz-Ortega*

Carvedilol and tamsulosin, both belonging to the family of adrenergic receptor antagonists, have been proposed in multiple recent studies (both in vitro and in vivo) for the treatment of liver and kidney fibrosis. However, there are reports of possible side effects that contradict its therapeutic properties in chronic liver damage. Furthermore, there is insufficient toxicological information on these drugs to ensure their safety. The present study investigates the signaling pathways activated during endoplasmic reticulum stress using a cell model derived from hepatocytes. Our MTT assay results suggest that both drugs reduce cell viability in a time-dependent manner, with a tendency for proliferation at higher concentrations. The study of gene expression kinetics for UPR markers revealed a moderate response in the PERK-ATF4 and IRE1-XBP1 branches after 12 hours of treatment. GRP78 showed an increase in expression within the initial hours of treatment; however, no significant differences in its synthesis were observed when evaluated with Western blot. Finally, the study found that tamsulosin did not alter the rate of protein synthesis, while carvedilol briefly reduced it. Our findings suggest that both carvedilol and tamsulosin upregulate genes associated with the response to misfolded proteins, but this alone is insufficient to trigger the cell death response.