Cardioprotective effects of acetate supplementation against fructose-induced cardiac injury in pregnant Wistar rats

Background: High fructose intake during pregnancy exacerbates cardiometabolic risk through lipid dysregulation and oxidative stress, with limited therapeutic strategies. Objective: This study investigated the cardioprotective effects of acetate supplementation against fructose-induced cardiac injury in pregnant Wistar rats, focusing on VEGF/PI3K signaling, redox balance, and lipid metabolism. Methods: Thirty female Wistar rats with a mean weight of 135 ± 15g were divided into pregnant (P) and non-pregnant (NP) cohorts (n = 15 each). Pregnant and non-pregnant rats were randomly assigned to three treatment groups (n = 5/group): control (standard chow and water), fructose (10% w/v fructose in drinking water ad libitum), and fructose + acetate (10% w/v fructose in drinking water + oral sodium acetate 200 mg/kg/day via gavage). Treatments were administered concurrently throughout the 3-week experimental period. After three weeks of treatment, rats were euthanized with ketamine (90 mg/kg) and xylazine (10 mg/kg) intramuscularly in the thigh. Blood was collected via cardiac puncture, and hearts were excised, homogenized, and analyzed for free fatty acid (FFA), triglyceride (TG), total cholesterol (TC), malondialdehyde (MDA), 4-Hydroxy-2-nonenal (4-HNE), adeosine deaminase (ADA), xanthine oxidase (XO), uric acid (UA), Reduced Glutathione/Oxidized Glutathione (GSH/GSSG) ratio, glucose-6-phosphate dehydrogenase (G6PDH), vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K.). Data were analyzed using two-way Analysis of Variance (ANOVA), (p < 0.05). Results: Fructose significantly elevated cardiac FFA, TG, TC, MDA, 4-HNE, ADA, XO, and UA levels, which were more pronounced in the pregnant rats with an accompanying decreased cardiac GSH/GSSG ratio, G6PDH activity, PI3K, and VEGF levels. Acetate co-administration normalised lipid profiles, restored redox homeostasis, and increased VEGF/PI3K levels, with pregnancy amplifying both fructose toxicity and acetate protection. Conclusion: Fructose exacerbates pregnancy-associated cardiac vulnerability via lipid overload and oxidative stress. Acetate confers cardio-protection, which is accompanied by increased VEGF/PI3K and antioxidant levels, positioning it as a promising nutraceutical strategy for gestational cardiometabolic disorders.