Affiliation:
1. Department of Pharmacology SVKM's Dr. Bhanuben Nanavati College of Pharmacy Mumbai India
2. Department of Pharmaceutical Chemistry SVKM's Dr. Bhanuben Nanavati College of Pharmacy Mumbai India
Abstract
AbstractMammalian target of Rapamycin C1 (mTORC1) inhibition limits plaque progression in atherosclerosis. The present study evaluated the protective effect of sulfamethizole on poloxamer 407‐induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition. Poloxamer 407 (P‐407) (0.5 g/kg body weight) was administered intraperitoneally to male C57BL/6 mice every third day for 148 days to induce chronic hyperlipidemia. From Day 121 to 148, animals were additionally administered Sulfamethizole (5, 10, and 50 mg/kg, p.o.), Rapamycin (0.5 mg/kg, positive control), or vehicle (1 ml/kg). Plasma lipid levels were measured on Days 120 and 148. Upon sacrifice, histological studies were performed, and aortic tissue interleukin (IL)‐6, tumor necrosis factor‐α (TNF‐α), and mTOR levels were evaluated. A molecular docking study was carried out to mimic the interaction of sulfamethizole with mTOR protein. Chronic P‐407 administration significantly (p < 0.001) elevated plasma lipid levels, compared with those of the normal control group. Chronic hyperlipidemia resulted in increased tunica intima thickness, collagen deposition, and IL‐6, TNF‐α, and mTOR levels. Treatment with Sulfamethizole attenuated these parameters significantly in a dose‐dependent manner. Molecular docking studies showed a significant interaction of Sulfamethizole with mTOR. In conclusion, this study suggests that sulfamethizole significantly limits poloxamer 407‐induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition.
Subject
Health, Toxicology and Mutagenesis,Toxicology,Molecular Biology,Molecular Medicine,Biochemistry,General Medicine
Cited by
1 articles.
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