Sesamin exerts renoprotective effects by enhancing NO bioactivity in renovascular hypertensive rats fed with high-fat-sucrose diet.
In the present study, we aimed to evaluate the protective effect of sesamin on kidney damage and renal endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat-sucrose diet (2K1C rats on HFS diet). Sesamin was intragastrically administered to 2K1C rats on HFS diet for eight weeks. Then, we measured the levels of serum hydrogen peroxide (H₂O₂), total antioxidant capability (T-AOC), renal malonaldehyde (MDA), total-erythrocuprein (T-SOD) and glutathione peroxidase (GSH-P(X)). The expressions of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in the left and right renal cortexes were detected by Western blotting. Pathological changes in the left and right renal cortexes were observed by periodic acid-schiff staining (PAS) and Masson's staining. Treatment with sesamin (120 and 60mg/kg⁻¹·d⁻¹) in 2K1C rats on HFS diet improved renal function, corrected structural abnormalities, and attenuated renal oxidative stress. Furthermore, sesamin increased eNOS protein expression and reduced nitrotyrosine and p47phox protein expression. These results demonstrated that long-term treatment with sesamin had renoprotective effect and improved renal endothelial dysfunction via upregulation of eNOS expression and reduction of NO oxidative inactivation in both clipped and contralateral kidneys of 2K1C rats on HFS diet, and sesamin may have a favorably therapeutic value in treating chronic kidney disease in patients with hypertension and hyperlipemia.
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Xiang-Qi
XQ
Wu
Xiang
X
Kong
Yong
Y
Zhou
Kai
K
Huang
Jie-Ren
JR
Yang
Xin-Li
XL
Li
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D004149:Dioxoles / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017705:Lignans / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000959:Antihypertensive Agents; D000975:Antioxidants; D019422:Dietary Sucrose; D004149:Dioxoles; D000960:Hypolipidemic Agents; D017705:Lignans; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C054125:sesamin