Evaluation of the antihypertensive and antihyperlipidaemic effects of a pyrimidine derivative in preventing cardiometabolic risk.

BACKGROUND AND PURPOSE: Cardiovascular diseases cause about 20.5 million deaths, making them one of the primary causes of death worldwide. Hypertension and hyperlipidaemia are major modifiable risk factors for cardiovascular diseases, and current medications pose significant side effects and often fail to prevent long-term complications, highlighting the need for alternative therapies. This study evaluates the therapeutic potential of BN2 ((Z)-N-(4-(4-chlorophenyl)-6-(4-fluorophenyl)pyrimidin-2-yl)-1-(furan-2-yl)methanimine) against sodium fluoride (NaF)-induced cardiometabolic injury.

EXPERIMENTAL APPROACH: In zebrafish models exposed to NaF, reactive oxygen species (ROS) and the antioxidant enzyme activities (SOD, CAT, GST, GPx) were measured. Cholesterol and triglyceride accumulation were observed and quantified using HPLC. Cardiac function was evaluated by measuring heart rate, pericardial oedema, erythrocyte damage and scoring heart tissue section histopathologically. At the molecular level, gene expression of important hypertensive and hyperlipidaemic markers (agtr1a, nppa, postnb, fn1a and col11a1b) was measured by RT-qPCR analysis.

KEY

RESULTS

BN2 reduced ROS levels, enhanced antioxidant enzyme activities (SOD, CAT, GST, GPx) and decreased lipid accumulation. It ameliorated NaF-induced bradycardia, reduced pericardial oedema, normalized erythrocyte function and lowered cardiac tissue damage. In molecular terms, BN2 down-regulated the expression of agtr1a, nppa, fn1a, postnb and col11a1b and up-regulated mstnb and bcl2a. BN2 efficacy was similar to captopril throughout all evaluated parameters.

CONCLUSION AND IMPLICATIONS: Our results demonstrate that, in zebrafish models, BN2 effectively modulates oxidative stress, cardiac damage, lipid accumulation and inflammation, establishing it as a promising therapeutic candidate for preventing cardiovascular diseases.