Selected Antihypertensive Agents and their Fixed-Dose Combinations Effectively Ameliorate Trastuzumab-Mediated Cardiac Dysfunctions in Rats
| dc.contributor.author | Akinsola Akinyele O | |
| dc.date.accessioned | 2025-05-09T11:48:42Z | |
| dc.date.available | 2025-05-09T11:48:42Z | |
| dc.date.issued | 2021-06 | |
| dc.description.abstract | This study evaluates the therapeutic potentials of selected antihypertensive drugs [valsartan (VAL), amlodipine (ADP), lisinopril (LSP) and their fixed-dose combinations [(amlodipine + lisinopril) (ADP + LSP) and (valsartan + lisinopril) (VAL + LSP)] in ameliorating trastuzumab (TZM)‑induced cardiovascular dysfunctions in experimental rats. In-bred female Wistar rats were randomly allotted into 10 groups of 6 rats per group. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) as well as electrocardiogram (ECG) of the treated rats were measured using non-invasive procedures on days 1 and 7 of the experiment, following which the treated rats were sacrificed under light inhaled diethyl ether and histopathological evaluation of all treated hearts was done. Results showed that repeated TZM treatment profoundly (p<0.05) raised SBP, DBP and MAP values from 115.0 ± 17.1 mmHg, 85.1 ± 15.1 mmHg and 94.7 ± 15.5 mmHg, respectively on day 1 to 127.7 ± 27.8 mmHg, 87.4 ± 27.3 mmHg and 100.5 ± 26.4 mmHg, respectively, on day 7. Oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations profoundly (p<0.05) attenuated increases in the SBP, DBP and MAP values with the most significant attenuation mediated by the fixed-dose VAL + LSP combination at the SBP, DBP and MAP values of 103.8 ± 20.6 mmHg, 65.5 ± 18.8 mmHg, and 77.9 ± 18.7 mmHg, respectively. TZM treatment also profoundly (p<0.05) prolonged the QT and corrected QT intervals from 85.0 ± 11.5 ms and 161.6 ± 20.3 ms, respectively, on day 1 to 110.2 ± 21.5 ms and 226.5 ± 41.5 ms, respectively, on day 7. However, these QT and corrected QT interval prolongations were effectively and profoundly attenuated by oral pretreatments with VAL, ADP, LSP and their fixed-dose combinations. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, these histopathological changes were reversed with oral pretreatments with ADP, LSP, VAL and fixed-dosed [(ADP + LSP) and (VAL + LSP)] combinations although fixed-dose VAL + LSP was associated with histopathological lesions of coronary arterial wall cartilaginous metaplasia. Overall, this study revealed the promising therapeutic potentials of VAL, ADP, LSP and their fixed-dose combinations as repurposed drugs for the prevention of TZM-mediated cardiac dysfunctions. | |
| dc.identifier.uri | https://repository.run.edu.ng/handle/123456789/4485 | |
| dc.language.iso | en | |
| dc.publisher | Nigerian Journal of Physiological Sciences | |
| dc.relation.ispartofseries | 36 | |
| dc.title | Selected Antihypertensive Agents and their Fixed-Dose Combinations Effectively Ameliorate Trastuzumab-Mediated Cardiac Dysfunctions in Rats | |
| dc.type | Article |