TITLE

The renoprotective effect of l-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression

AUTHOR(S)
Zambrano, Sonia; Blanca, Antonio; Ruiz-Armenta, María; Miguel-Carrasco, José; Revilla, Elisa; Santa-María, Consuelo; Mate, Alfonso; Vázquez, Carmen
PUB. DATE
September 2013
SOURCE
European Journal of Nutrition;Sep2013, Vol. 52 Issue 6, p1649
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: 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.
ACCESSION #
89769885

 

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