Abstract
BACKGROUND: This study investigated the renoprotective effects of compound 21 (C21) and empagliflozin (EMPA) individually and in combination in an Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rat model. The objective of this study was to evaluate their impact on oxidative stress (OS), biochemical markers, and histopathological changes in renal tissues. METHODS: Male Sprague–Dawley rats were divided into five groups: control, hypertension (HT), HT + C21, HT + EMPA, and HT + C21 + EMPA. Hypertension was induced by intraperitoneal L-NAME administration. Biochemical analyses of kidney tissue and histopathological evaluations were conducted to assess the treatment effects. RESULTS: Both C21 and EMPA significantly reduced the levels of OS markers, such as malondialdehyde, while increasing the levels of antioxidants, such as total antioxidants and glutathione. Compared with the individual treatments, the combination of C21 and EMPA exhibited superior efficacy in mitigating OS by significantly increasing superoxide dismutase and glutathione peroxidase activities. Furthermore, these treatments alleviated histopathological damage, including glomerular collapse, tubular degeneration, and interstitial inflammation, which were prominent in the HT group. The combined therapy group presented nearly normal histological structures in kidney tissues, with reduced inflammation and cellular damage. Urinary biochemical markers also reflected improved renal function in the treated groups, particularly in the combined therapy group. These findings indicate that the synergistic effects of C21 and EMPA enhance their protective impact on renal tissues. CONCLUSION: C21 and EMPA demonstrated significant renoprotective effects in this HT model by reducing OS, enhancing antioxidant defenses, and mitigating renal tissue damage. Their combined administration offered synergistic benefits, highlighting their potential as a therapeutic strategy for hypertension-induced renal injury. Further research is warranted to validate these findings in clinical settings.