Isoflavone treatment attenuates cardiovascular-kidney-metabolic (CKM) syndrome symptoms in an experimental model of ovariectomized rats.

Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome represents an integrated spectrum of obesity, type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease, driven by shared metabolic, inflammatory, and fibrotic mechanisms. Menopause-related estrogen deficiency exacerbates these disturbances, increasing susceptibility to metabolic syndrome and renal injury. This study investigated whether dietary supplementation with soy isoflavones attenuates obesity-associated kidney injury in ovariectomized rats exposed to a high-fat, high-caloric diet. Female Wistar rats underwent bilateral ovariectomy and were assigned to control diet, hipercaloric diet (DH), or DH supplemented with isoflavones (DH+ISO). Metabolic, biochemical, oxidative stress, histopathological, and inflammatory parameters were evaluated over 120 days. The DH diet induced weight gain, hypertension, dyslipidemia, hyperglycemia, impaired renal function, increased oxidative stress, and tubulointerstitial injury, consistent with a CKM phenotype. Isoflavone supplementation did not prevent diet-induced weight gain but attenuated systolic blood pressure elevation and improved lipid and glycemic profiles. Renal function was partially preserved in DH+ISO rats, as evidenced by lower plasma creatinine levels, improved creatinine clearance, reduced urea levels, and decreased urinary peroxide excretion compared with DH animals. Histopathological analysis revealed persistent tubular injury in both DH groups, although inflammatory and oxidative markers were attenuated in isoflavone-treated rats. Immunohistochemistry demonstrated reduced renal IL-6 expression in the DH+ISO group, accompanied by trends toward decreased macrophage infiltration and IL-1{beta} expression. Collectively, these findings indicate that soy isoflavones mitigate metabolic, inflammatory, and oxidative pathways implicated in obesity-related kidney injury in a postmenopausal experimental model. Isoflavone supplementation may represent a complementary therapeutic strategy for attenuating CKM-related renal damage associated with modern diets and estrogen deficiency.