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

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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.

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Acknowledgments

This study was supported by Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación, PN de I+D+I 2008-2011 (PS09/01395) and Consejería de Salud, Junta de Andalucía (PI-0034). S. Zambrano, J.L. Miguel-Carrasco, and A. Blanca were supported by the grants from Consejería de Salud, Junta de Andalucía (PI-0034), and Instituto de Salud Carlos III (FIS PS09/01395). We thank the University of Seville’s Centro de Investigación, Tecnología e Innovación (CITIUS) for its technical assistance. We are also grateful to Dra. A. Fortuño for her help with the determination of NADPH oxidase activity.

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, c/Profesor García González 2, 41012, Sevilla, Spain

    Sonia Zambrano, Antonio Jesús Blanca, María Victoria Ruiz-Armenta, José Luis Miguel-Carrasco, Alfonso Mate & Carmen María Vázquez

  2. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, c/Profesor García González 2, 41012, Sevilla, Spain

    Elisa Revilla & Consuelo Santa-María

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  1. Sonia Zambrano
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  2. Antonio Jesús Blanca
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  3. María Victoria Ruiz-Armenta
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  4. José Luis Miguel-Carrasco
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  5. Elisa Revilla
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  6. Consuelo Santa-María
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Correspondence to Consuelo Santa-María.

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Zambrano, S., Blanca, A.J., Ruiz-Armenta, M.V. et al. The renoprotective effect of l-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression. Eur J Nutr 52, 1649–1659 (2013). https://doi.org/10.1007/s00394-012-0470-x

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