Ebselen attenuates selected cardiac and vascular alterations in rats exposed to a cholesterol/cholic acid diet.

Hypercholesterolemia (HCT) is a major risk factor for cardiovascular diseases and promotes myocardial and vascular injury primarily through oxidative stress (OS)-mediated mechanisms. Ebselen (EBS), a glutathione peroxidase-mimetic antioxidant, has been associated with attenuation of tissue injury in several experimental OS-related models; however, its short-term effects on selected outcomes in HCT-associated cardiovascular damage remain unclear. Twenty-four male Wistar albino rats were randomly assigned to three groups: Control, cholesterol/cholic-acid diet (HCT), and the same diet treated with EBS (HCT+EBS). Rats in the HCT-designated groups received a diet containing 2% cholesterol and 0.5% cholic acid for six weeks; serum lipids were not measured. EBS (10 mg/kg/day, intraperitoneal) was administered during the final week. Hemodynamic and electrocardiographic parameters, serum injury biomarkers, myocardial oxidative-stress parameters, and cardiac and descending-aortic histopathology were assessed. Relative to Control, the cholesterol/cholic-acid diet group designated HCT showed higher myocardial lipid peroxidation, lower superoxide dismutase (SOD) activity, higher serum myoglobin and lactate dehydrogenase, and more severe cardiac and aortic histopathological alterations. Compared directly with HCT, HCT+EBS showed lower myocardial malondialdehyde, higher SOD activity, lower injury biomarkers, and less severe histopathological alterations. Because serum lipids were not measured, these differences cannot be separated from a possible EBS-associated difference in lipid profile. EBS administration also induced a marked hypotensive response: systolic blood pressure was significantly lower in HCT+EBS than in both HCT and Control. Short-term EBS administration was associated with selected biochemical and histopathological differences in rats exposed to a cholesterol/cholic-acid diet. However, the lipid phenotype was not confirmed, and a possible EBS-associated difference in serum lipids cannot be excluded. Together with the absence of an EBS-only control group, this prevents attribution of the findings specifically to direct antioxidant actions of EBS or interpretation as therapeutic efficacy.