Casein or soy protein supplementation protects against hepatotoxicity in hypercholesterolemic rats treated with rosuvastatin
Mosaad A. Abdel-Wahhab1(), Aziza A. El-Nekeety1, Mona A. Hassan2, Sekena H. Abdel-Aziem3, Nabila S. Hassan4
Food Toxicology and Contaminants Department, National Research Centre, Cairo 12622, Egypt
Food Evaluation and Food Science Department, National Organization for Drug Control and Research, Giza 12553, Egypt
Cell Biology Department, National Research Centre, Cairo 12622, Egypt
Pathology Department, National Research Centre, Cairo 12622, Egypt
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Highlights
(1) Rosuvastatin (Rsv) improves lipid profile in hypercholesterolemic rats (HCD).
(2) Rsv induces hepatic and renal oxidative stress and disturbs gene expression in HCD.
(3) Dietary soy protein and casein improved all the tested parameters in HCD.
(4) Soy protein was more effective than casein.
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Rosuvastatin (Rvs) is used for hypercholesterolemia therapeutic but it induces adverse effects including hepatotoxicity. We evaluated the hepatoprotective role of casein and soy protein in hypercholesterolemic rats received Rvs. Rvs improved lipid profile in hypercholesterolemic rats, but it disturbed the liver and kidney indices, oxidative stress markers, the hepatic mRNA expression of SREBP-1c, SREBP-2, FAS, and ACC-1 and the histopathological picture in hypercholesterolemic rats. Casein and soy protein improved the all the tested parameters, the histological picture, and modified the related gene expressions. Soy protein was more effective than casein and both of them can protect against Rvs-induced hepatotoxicity under hypercholesterolemic conditions.
Abstract
Rosuvastatin (Rvs) is used for hypercholesterolemia therapeutic but it induces adverse effects including hepatotoxicity. This study aimed to evaluate the hepatoprotective role of casein and soy protein in hypercholesterolemic rats received Rvs. Seven groups of male Wistar rats were treated for 8 weeks including; control group, high-cholesterol diet (HCD) group, the groups treated orally with casein or soy protein (300 mg/kg bw) suspended in distilled water, the group received HCD for 4 weeks and treated orally with Rvs (20 mg/kg bw) for another 4 weeks, and the groups received HCD for 4 weeks and treated orally with casein or soy protein for another 4 weeks. Blood and tissue samples were collected for different assays. The results indicated that Rvs improved lipid profile in hypercholesterolemic rats, but it disturbed the liver and kidney indices, oxidative stress markers, the hepatic mRNA expression of SREBP-1c, SREBP-2, FAS, and ACC-1 and the histopathological picture in hypercholesterolemic rats. Casein and soy protein improved the all the tested parameters, the histological picture, and mRNA expression of the tested genes, and soy protein was more effective than casein. Casein and soy protein supplementation can protect against Rvs-induced hepatotoxicity under hypercholesterolemic conditions.
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Abdel-Wahhab MA, El-Nekeety AA, Hassan MA, et al. Casein or soy protein supplementation protects against hepatotoxicity in hypercholesterolemic rats treated with rosuvastatin. Food & Medicine Homology, 2025,https://doi.org/10.26599/FMH.2026.9420088
Lipid metabolism related gene expression in rat livers. The mRNA levels of hepatic SREBP-1c (A), SREBP-2 (B), FAS (C) and ACC1 (D) were determined by quantitative real time PCR analysis. Results were normalized to GAPDH and β-actin expression and then expressed as fold changes relative to gene expression. Data are expressed as mean ± SE. Means with different letters are significantly different at P ≤ 0.05.
Photomicrographs of the liver sections of (A) control rats showing normal histology of hepatic cells (H) with preserved nucleus, cytoplasm and hepatocytes which were arrayed in well-formed nucleus cords around the central vein (CV), (B) rats treated with Chol showing the fibrous tissues around the portal tract, hepatocytes have marked fatty (black arrow), hydropic degeneration (yellow-arrow) and necrosis (n), (C) rats treated with casein showing the hepatocytes around the central vein are nearly normal (inset) and focal necrosis with fibrosis around portal tract (pt), (D) rats treated with soy protein showing nearly normal hepatic architecture around blood vessels, rats treated with Chol plus Rvs (E), Chol plus Rvs and casein (F) and Chol plus Rvs and soy protein (G) showing marked improvement in hepatic cells (H) and blood vessels (bs). Scale bar: ×400.
Photomicrographs of sections in the rat kidney from (A) control group, (B) Chol-treated group, (C) casein-treated group and (D) soy protein-treated group showing no histological changes in kidney tubules and glomeruli. The kidney sections of (E) Chol plus Rvs-treated group, (F) Chol plus Rvs and casein-treated group and (G) Chol plus Rvs and soy protein-treated group showing few renal histological changes where glomerular mesengial cells are expanded and renal tubules are dilated. Scale bar: ×400.