title: The renoprotective effect of L-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression.
abstract: OBJECTIVE
  Arterial hypertension is associated with a high production of reactive oxygen species and a decrease in the antioxidant defense systems. Based on the lack of toxicity of L-carnitine (LC) and previous studies reporting beneficial effects of this compound in experimental models of hypertension, the aim of this work was to test the hypothesis that LC might protect the kidney against hypertension-induced oxidative damage, as well as to investigate the mechanisms involved in this effect. To this end, specific activities and protein/mRNA expression of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, and superoxide dismutase), and those of NADPH oxidase (the main responsible for superoxide anion production in renal tissue) have been measured in renal cortex homogenates from NG-nitro-L-arginine methyl ester (L-NAME)-treated rats and control normotensive rats. In addition, components of the renin-angiotensin system (RAS) and redox-sensitive transcription factors (NF-κB, Nrf2, and PPARα) have also been evaluated.
  
  
  METHODS
  Male Wistar rats aged 6-8 weeks were divided into four groups of six animals each: (1) control, normotensive Wistar rats (with free access to tap water); (2) Wistar rats subjected to treatment with 25 mg of L-NAME/kg body weight/day dissolved in the drinking water, in order to develop L-NAME-induced hypertension; (3) Wistar rats subjected to treatment with 400 mg of LC/kg body weight/day (also dissolved in the drinking water); and (4) L-NAME-treated rats subjected to simultaneous treatment with LC at the indicated doses.
  
  
  RESULTS
  The beneficial effect of LC supplementation on oxidative damage in the renal cortex of hypertensive rats reversed hypertension-associated renal function damage and produced an upregulation of both antioxidant enzymes and eNOS, and with a downregulation of both NADPH oxidase and RAS components. LC improves the oxidative stress response through a specific modulation of NF-κB, Nrf2, and PPARα transcription factors. Thus, the low production of superoxide anions, subsequent to NADPH oxidase inhibition, might act by increasing the expression of Nrf2 and PPARα and by decreasing that of NF-κB, which, in turn, would enhance the antioxidant defense systems.
  
  
  CONCLUSIONS
  Our results might support the use of LC to prevent hypertension-induced renal damage.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, c/Profesor García González 2, 41012 Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.forename: Antonio Jesús
authors.initials: AJ
authors.lastname: Blanca
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Ruiz-Armenta
authors.forename: José Luis
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.forename: Elisa
authors.initials: E
authors.lastname: Revilla
authors.forename: Consuelo
authors.initials: C
authors.lastname: Santa-María
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002331:Carnitine / Q000494:pharmacology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D047493:PPAR alpha; D013481:Superoxides; D005979:Glutathione Peroxidase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005980:Glutathione Reductase; D002331:Carnitine; D019331:NG-Nitroarginine Methyl Ester