L-Carnitine Attenuates the Development of Kidney Fibrosis in Hypertensive Rats by Upregulating PPAR-γ

The development of renal fibrosis is a consequence of arterial hypertension. L-carnitine plays an essential role in the -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) in this effect. 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- in L-carnitine effect. An increase in the expression of collagen, transforming growth factor beta 1 (TGF-(1)), connective tissue growth factor (CTGF), Nox2, and Nox4 was found in the kidney of L-NAMEtreated rats. Hypertensive rats presented with an expansion of renal fibrotic areas, which was also accompanied by overexpression of proinflammatory cytokines, interleukin (IL)1, and IL-6. A reduction in the expression of PPAR- 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-(1) levels) and the pro-oxidative and proinflammatory status reported in L-NAME groups, with a concomitant increase in the expression of PPAR-. Furthermore, the antifibrotic effect of L-carnitine could be blocked by PPAR- inhibition. 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-dependent manner.