L-carnitine attenuates the development of kidney fibrosis in hypertensive rats by upregulating PPAR-γ - PubMed (original) (raw)
doi: 10.1093/ajh/hpt268. Epub 2014 Jan 11.
Affiliations
- PMID: 24413708
- DOI: 10.1093/ajh/hpt268
L-carnitine attenuates the development of kidney fibrosis in hypertensive rats by upregulating PPAR-γ
Sonia Zambrano et al. Am J Hypertens. 2014 Mar.
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.
Keywords: L-NAME; L-carnitine; PPAR.; blood pressure; fibrosis; hypertension; kidney.
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