Activation of 20-HETE/PPARs involved in reno-therapeutic effect of naringenin on diabetic nephropathy. (1st July 2019)

• Record Type: Journal Article
• Authors: Ding, Shumei; Qiu, Hongmei; Huang, Jiajun; Chen, Rongchun; Zhang, Jie; Huang, Bo; Zou, Xunliang; Cheng, Oumei; Jiang, Qingsong
• Is Part Of: Chemico-biological interactions. Volume 307(2019)
• Page Start: 116
• Page End: 124
• Publication Date: 2019-07-01
• Subjects: Diabetic nephropathy -- Naringenin -- PPARs -- CYP4A -- 20-HETE; AA arachidonic acid -- BCA bicinchoninic acid -- BUN blood urea nitrogen -- CMC-Na carboxymethylcellulose sodium -- COX cyclooxygenase -- CYP cytochrome P450 -- DM diabetes mellitus -- DMEM Dulbecco's modified Eagle's medium -- DMSO dimethyl sulfoxide -- DN diabetic nephropathy -- EETs epoxyeicosatrienoic acids -- FBG fasting blood glucose -- FBS fetal bovine serum -- 20-HETE 20-hydroxyeicosatetraenoic acid -- HG high glucose -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- OD optical density -- PPARs peroxisome proliferators-activated receptors -- Scr serum creatinine -- STZ streptozotocin; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.05.004
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Naringenin is a flavanone compound found in citrus fruits. Recent researches showed that naringenin has many potentially pharmacological effects. However, the therapeutic effect and the potential mechanism of naringenin on diabetic nephropathy (DN) remain to be elucidated. DN model was established by a high-fat diet combined with streptozotocin (STZ), which was confirmed by the levels of fasting blood glucose (FBG, more than 11.1 mmol/L) and urinary albumin (10 times higher than the normal mice). After 5 weeks of STZ injection, the DN was developed in model mice. Then naringenin (25 or 75 mg/kg·d) were supplemented for 4 weeks. At the end of the experiment, the injury of the renal function and structure was deteriorated. Concomitantly, peroxisome proliferators-activated receptors (PPARs) protein expression was down-regulated, and CYP4A expression and 20-hydroxyeicosatetraenoic acid (20-HETE) level were reduced in DN mice. Naringenin administration improved the renal damage of DN mice, and up-regulated PPARs expression, increased CYP4A-20-HETE level. Consistent with the results of in vivo, glucose at 30 mmol/L (high glucose, HG) significantly induced cell proliferation and hypertrophy in NRK-52E cells, following the reductive PPARs protein expression and the downward CYP4A-20-HETE level. Naringenin (0.01, 0.1, 1 μmol/L) reversed these changes induced by HG in a dose-dependent manner. HET0016, a selective inhibitor of 20-HETE synthase, partially blocked the effects of naringenin. In conclusion, naringenin has a therapeutic effect on DN, which may be, at least partly, related to the activation of CYP4A-20-HETE and the up-regulation of PPARs. Graphical abstract: Image 1 Highlights: Down-regulation of 20-HETE/PPARs is involved in pathological process of DN. Naringenin has reno-therapeutic effect on DN. Reno-protection of naringenin on DN may be related to 20-HETE/PPARs activation.