Histopathological and Computational Histomorphometric Evaluation of the Protective Effects of Quercetin in High-Fat High-Sugar Diet-Induced Metabolic Syndrome in Wistar Rats

Abstract

Metabolic syndrome is increasingly associated with obesity, insulin resistance, type 2 diabetes mellitus, cardiovascular disease, and multi-organ dysfunction. This study investigated the protective effects of quercetin against high-fat/high-sugar (HFHS) diet-induced metabolic, hepatic, and renal alterations in Wistar rats. Adult rats (120–150 g) were randomly assigned into five groups (n = 6/group): control, HFHS, HFHS + quercetin 100 mg/kg (HFHS/Q100), HFHS + quercetin 200 mg/kg (HFHS/Q200), and HFHS + metformin 25 mg/kg (HFHS/MET). Metabolic, biochemical, histopathological, quantitative histomorphometric, colour histogram, and computational tissue analyses were performed. HFHS feeding significantly increased body weight, feed intake, blood glucose, plasma insulin, leptin, total cholesterol, triglycerides, LDL, malondialdehyde, TNF-α, liver enzymes, urea, and creatinine, while reducing adiponectin, total antioxidant capacity, and IL-10 levels. Histopathological examination revealed marked hepatic and renal structural alterations including hepatocellular vacuolation, sinusoidal distortion, tubular degeneration, glomerular disruption, and reduced tissue compactness. Quantitative histomorphometric and computational analyses demonstrated treatment-dependent alterations in cellular profile density, stained area fraction, optical density, texture entropy, and RGB staining characteristics. Quercetin supplementation significantly ameliorated HFHS-induced metabolic, oxidative, inflammatory, hepatic, and renal abnormalities. Quercetin improved glucose regulation, lipid profile, antioxidant status, adipokine balance, and organ integrity while partially restoring hepatic and renal histoarchitecture. Overall, quercetin demonstrated significant hepatoprotective and renoprotective effects against HFHS-induced metabolic syndrome, likely mediated through antioxidant, anti-inflammatory, and metabolic regulatory mechanisms.