title: L-carnitine attenuates the development of kidney fibrosis in hypertensive rats by upregulating PPAR-γ.
abstract: BACKGROUND
  The development of renal fibrosis is a consequence of arterial hypertension. L-carnitine plays an essential role in the β-oxidation of fatty acids, and we have previously demonstrated hypotensive, antioxidant, and anti-inflammatory effects of L-carnitine in arterial hypertension. This work aims to analyze the effect of L-carnitine on renal fibrosis and to explore the participation of peroxisome-proliferator activated receptor (PPAR)-γ in this effect.
  
  
  METHODS
  Four groups or rats were used: control, treated with L-carnitine, treated with L-NAME, and treated with L-carnitine + L-NAME. Cultured rat kidney cells were also used to examine the role of PPAR-γ in L-carnitine effect.
  
  
  RESULTS
  An increase in the expression of collagen, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), Nox2, and Nox4 was found in the kidney of L-NAME-treated rats. Hypertensive rats presented with an expansion of renal fibrotic areas, which was also accompanied by overexpression of proinflammatory cytokines, interleukin (IL)-1β, and IL-6. A reduction in the expression of PPAR-γ and in that of anti-inflammatory IL-10 was found in the kidney of these rats. Simultaneous treatment with L-carnitine attenuated the renal fibrosis (which correlated with a reduction of plasma TGF-β1 levels) and the pro-oxidative and proinflammatory status reported in L-NAME groups, with a concomitant increase in the expression of PPAR-γ. Furthermore, the antifibrotic effect of L-carnitine could be blocked by PPAR-γ inhibition.
  
  
  CONCLUSIONS
  This study confirms the efficacy of L-carnitine against hypertension-associated renal fibrosis from in vivo and in vitro studies and suggests that the L-carnitine effect occurs in a PPAR-γ-dependent manner.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Blanca
authors.forename: María V
authors.initials: MV
authors.lastname: Ruiz-Armenta
authors.forename: José L
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.forename: Miguel
authors.initials: M
authors.lastname: Arévalo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005355:Fibrosis; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C526316:CCN2 protein, rat; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D047495:PPAR gamma; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D055513:Connective Tissue Growth Factor; D003094:Collagen; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D002331:Carnitine; D019331:NG-Nitroarginine Methyl Ester
keywords: L-NAME; L-carnitine; PPAR.; blood pressure; fibrosis; hypertension; kidney