Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Toxicol Appl Pharmacol. 2013 Dec 1;273(2):314-24. doi: 10.1016/j.taap.2013.09.004. Epub 2013 Sep 14.


Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.

Keywords: Diabetic nephropathy; Fibronectin; TGF-β; Tocotrienol rich fraction; Tocotrienols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / prevention & control
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / prevention & control
  • Gene Expression Regulation*
  • Lipids / blood*
  • Male
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use
  • Protective Agents / isolation & purification
  • Protective Agents / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Tocotrienols / isolation & purification
  • Tocotrienols / therapeutic use*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / biosynthesis*


  • Lipids
  • Plant Extracts
  • Protective Agents
  • Tocotrienols
  • Transforming Growth Factor beta