Fenretinide inhibits macrophage inflammatory mediators and controls hypertension in spontaneously hypertensive rats via the peroxisome proliferator-activated receptor gamma pathway

Ching Han Lin, Shang Yu Lee, Chun Cheng Zhang, Ye Fong Du, Hao Chang Hung, Hung Tsung Wu, Horng Yih Ou

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Fenretinide is a novel anticancer agent reported to exhibit anti-invasive and antimetastatic activities. It has also been shown to improve obesity and diabetes, although the effects of fenretinide on hypertension are still unknown, and the detailed mechanisms remain unclear. In this study, we have shown that treatment with lipopolysaccharide (LPS) decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in RAW264.7 macrophages, and pretreatment with fenretinide reversed the effect of LPS on PPARγ expression. In addition, LPS-induced pro-inflammatory cytokine production, including tumor necrosis factor-α, interleukin 6, and monocyte chemoattractant protein 1 were dose-dependently reversed by fenretinide, and the effects of fenretinide on LPS-induced pro-inflammatory cytokine production were blocked by treatment with PPARγ antagonist. Moreover, fenretinide decreased LPS-induced inducible nitric oxide synthase expression and nitrogen oxide production. These effects were blocked by the pretreatment with PPARγ antagonist in a dose-dependent manner, indicating fenretinide activated PPARγ to exert anti-inflammation activity. In view of the role of inflammation in hypertension and the anti-inflammatory action of fenretinide, we found that administration of fenretinide in spontaneously hypertensive rats significantly decreased blood pressure. Taken together, these results indicate that fenretinide might be a potent antihypertensive agent that works by suppressing inflammation via activating PPARγ.

Original languageEnglish
Pages (from-to)3591-3597
Number of pages7
JournalDrug Design, Development and Therapy
Volume10
DOIs
Publication statusPublished - Nov 1 2016
Externally publishedYes

Fingerprint

Fenretinide
PPAR gamma
Inbred SHR Rats
Macrophages
Peroxisome Proliferator-Activated Receptors
Hypertension
Lipopolysaccharides
Inflammation
Cytokines
Chemokine CCL2
Nitric Oxide Synthase Type II
Antineoplastic Agents
Antihypertensive Agents
Interleukin-6
Nitric Oxide
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Obesity

Keywords

  • Fenretinide
  • Hypertension
  • Inflammation
  • Macrophage
  • Peroxisome proliferator-activated receptor γ

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Fenretinide inhibits macrophage inflammatory mediators and controls hypertension in spontaneously hypertensive rats via the peroxisome proliferator-activated receptor gamma pathway. / Lin, Ching Han; Lee, Shang Yu; Zhang, Chun Cheng; Du, Ye Fong; Hung, Hao Chang; Wu, Hung Tsung; Ou, Horng Yih.

In: Drug Design, Development and Therapy, Vol. 10, 01.11.2016, p. 3591-3597.

Research output: Contribution to journalArticle

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