PPARα agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

Hou, Xiaotong; Shen, Ying H.; Li, Chuanbao; Wang, Fei; Zhang, Cheng; Bu, Peili; Zhang, Yun

doi:10.1016/j.bbrc.2010.03.043

Cited by 74 publications

(69 citation statements)

References 29 publications

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“…It tended to the same for Erk 1/2, too Fenofibrate has been shown to inhibit stress-activated kinases such as p38 or Jnk in cardiac hypertrophy models in vitro (De Silva et al 2009;Irukayama-Tomobe et al 2004). Similar observations were also made for p38 in the kidneys of hypertensive rats treated with fenofibrate (Hou et al 2010). Nonetheless the role of stress-activated 17 kinases in cardiac hypertrophy remains controversial.…”

Section: Discussionsupporting

confidence: 70%

Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload

et al. 2013

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Aims: Fenofibrate is a peroxisome proliferator associated receptor alpha agonist (PPAR) used clinically for the management of dyslipidemia and is a myocardial fatty acid oxidation stimulator. It has also been shown to have cardiac anti-hypertrophic properties but the effects of fenofibrate on the development of eccentric LVH and ventricular function in chronic left ventricular (LV) volume overload (VO) are unknown.This study was therefore designed to explore the effects of fenofibrate treatment in a VO rat model caused by severe aortic valve regurgitation (AR) with a focus on cardiac remodeling and myocardial metabolism.Main Methods: Male Wistar rats were divided in four groups (13-15 animals / group):Shams (S) treated with fenofibrate (F; 100 mg/kg/d PO) or not (C) and severe AR receiving or not fenofibrate. Treatment was started one week before surgery and the animals were sacrificed 9 weeks later.Key findings: AR rats developed severe LVH (increased LV weight) during the course of the protocol. Fenofibrate did not reduce LV weight. However, eccentric LV remodeling was strongly reduced by fenofibrate in AR animals. Fractional shortening was significantly less affected in ARF compared to ARC group. Fenofibrate also increased the myocardial enzymatic activity of enzymes associated with fatty acid oxidation while inhibiting glycolytic enzyme phosphofructokinase.Significance: Fenofibrate decreased LV eccentric remodeling associated with severe VO and helped maintain systolic function. Studies with a longer follow-up will be needed to assess the long-term effects of fenofibrate in chronic volume overload caused by aortic regurgitation.

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Section: Discussionsupporting

confidence: 70%

Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload

et al. 2013

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“…Among the natural ligands of PPAR, various eicosanoids, such as leucotriene B4, are generated during inflammatory responses [20,21]. In addition to these effects of ligand-bound PPAR on NF-B and c-jun, it has also been reported that ligand-free PPAR may inhibit the phosphorylation of p38 [22], a kinase that also promotes IFN transcription downstream of TCR stimulation [23]. Thus, we analyzed the in vitro response of human V9V2 T cells stimulated with a PPAR agonist, LY171883.…”

Section: Resultsmentioning

confidence: 99%

The PPARα pathway in Vγ9Vδ2 T cell anergy

Poupot

Boissard

Bétous

et al. 2014

Cellular and Molecular Biology Letters

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Phosphoantigens (PAgs) activate V9V2 T lymphocytes, inducing their potent and rapid response in vitro and in vivo. However, humans and nonhuman primates that receive repeated injections of PAgs progressively lose their V9V2 T cell response to them. To elucidate the molecular mechanisms of this in vivo desensitization, we analyzed the transcriptome of circulating V9V2 T cells from macaques injected with PAg. We showed that three PAg injections induced the activation of the PPAR pathway in V9V2 T cells. Thus, we analyzed the in vitro response of V9V2 T cells stimulated with a PPAR agonist. We demonstrated that in vitro PPAR pathway activation led to the inhibition of the BrHPP-induced activation and proliferation of human V9V2 T cells. Since the PPAR pathway is involved in the antigen-selective desensitization of human V9V2 T cells, the use of PPAR inhibitors could enhance cancer immunotherapy based on V9V2 T cells.

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“…Fenofibrate, therefore, prevents the activation of the nuclear factor-kB signaling pathway, which promotes the transcription of NADPH oxidase, TNF-a, and inducible nitric oxide synthase genes. 10,33,34 In addition, telmisartan along with fenofibrate protects renal cell by suppressing oxidative stress and proinflammatory mediators. Independent of AT1 receptor-blocking activity, telmisartan is responsible for the additional antioxidant and anti-inflammatory activities.…”

Section: Discussionmentioning

confidence: 99%

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

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It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

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PPARα agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

Cited by 74 publications

References 29 publications

Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload

Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload

The PPARα pathway in Vγ9Vδ2 T cell anergy

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

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