Renoprotective effect of myricetin restrains dyslipidemia and renal mesangial cell proliferation by the suppression of sterol regulatory element binding proteins in an experimental model of diabetic nephropathy

Eur J Pharmacol. 2014 Nov 15:743:53-62. doi: 10.1016/j.ejphar.2014.09.014. Epub 2014 Sep 18.

Abstract

Myricetin is a natural flavonoid used in various health management systems. In this present study myricetin tested to evaluate the effect on lipids and lipid metabolism enzymes in normal and streptozotocin (STZ) with cadmium (Cd) induced diabetic nephrotoxic rats. Diabetic nephrotoxic rats were significantly (P<0.05) increased the levels of urinary albumin and lipid profiles: total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoprotein (LDL), very low-density lipoproteins (VLDL), and decreased in the levels of high-density lipoproteins (HDL). In addition, the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were decreased significantly, whereas the 3-hydroxy 3-methylglutaryl coenzyme A (HmgCoA) reductase activity was increased. The upregulation of sterol regulatory element binding protein-1a (SREBP-1a), SREBP-1c, SREBP-2, transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF) and downregulation peroxisome proliferator-activated receptor alpha (PPAR-α) proteins expression levels were noticed. An administration of myricetin (1.0 mg/kg body weight (b/w)) for 12 weeks was brought the above parameters towards normal level. Histopathological study of kidney samples showed that extracellular mesangial matrix expansion, glomerulosclerosis and interstitial fibrosis in diabetic nephrotoxic rats was suppressed by myricetin treatment. Further our results indicate that administration of myricetin afforded remarkable protection against STZ-Cd induced alterations in lipid metabolism and thereby reduced the diabetic nephropathy in experimental rats.

Keywords: Cadmium; Diabetic nephropathy; Lipid metabolism; Myricetin; Myricetin (PubChem CID: 5281672); Steptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Fatty Acids, Nonesterified / metabolism
  • Flavonoids / pharmacology*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Lipid Metabolism / drug effects
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, LDL / metabolism
  • Male
  • Mesangial Cells / drug effects*
  • Mesangial Cells / metabolism
  • PPAR alpha / metabolism
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Sterol Regulatory Element Binding Proteins / metabolism*
  • Triglycerides / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Fatty Acids, Nonesterified
  • Flavonoids
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • PPAR alpha
  • Protective Agents
  • Sterol Regulatory Element Binding Proteins
  • Triglycerides
  • Vascular Endothelial Growth Factor A
  • myricetin
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Lipoprotein Lipase