Role of sodium tetraborate as a cardioprotective or competitive agent: Modulation of hypertrophic intracellular signals

Abstract

Boron is an essential trace element in cellular metabolism; however, the molecular mechanism of boron in the heart remains unclear. In this study, we examined the effect of sodium tetraborate (as a boron source) as a possible protective agent or competitive inhibitor of cardiac hypertrophy in an in vitro murine model. We evaluated different previously reported sodium tetraborate concentrations and found that 13 μM improves viability without affecting cellular structure. We demonstrated that cardiomyocytes pretreated with sodium tetraborate prevent cellular damage induced by isoproterenol (cardioprotective effect) by increasing proliferation rate and inhibiting apoptosis. In addition, a reduction in the expression of the α₁AR and β₁AR adrenergic receptors, as well as Erk1/2, was notable. Consequently, the expression of the early response genes c-myc, c-fos, and c-jun was delayed. Also, the expression of the transcription factors GATA-4, NFAT, Nkx2.5, and myogenin, involved in sarcomere synthesis, declined. In contrast, cardiomyocytes treated simultaneously with sodium tetraborate and isoproterenol did not increase their size (cytoplasmic gain), but an increase in apoptosis levels was observed; therefore, the proliferation rate was reduced. Although the mRNA expression levels of α₁AR, β₁AR, Erk1/2, and Akt1 were low at 24 h, their expression increased at 48 h. Notably, the mRNA expression levels of c-myc, c-fos, and c-jun were lower than those determined in the control, while the transcription factors GATA-4, MEF2c, Nkx2.5, NFAT, and CDK9 were detected in most cells. These results suggest that pretreatment with sodium tetraborate in cardiomyocytes inhibits the hypertrophic effect. However, sodium tetraborate attenuates isoproterenol-induced hypertrophy damage in cardiomyocytes when these two compounds are added simultaneously.