Naringenin ameliorates daunorubicin induced nephrotoxicity by mitigating AT1R, ERK1/2-NFκB p65 mediated inflammation

Vengadeshprabhu Karuppagounder, Somasundaram Arumugam, Rajarajan Amirthalingam Thandavarayan, Vigneshwaran Pitchaimani, Remya Sreedhar, Rejina Afrin, Meilei Harima, Hiroshi Suzuki, Kenji Suzuki, Masahiko Nakamura, Kazuyuki Ueno, Kenichi Watanabe

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Inflammation and oxidative stress play important roles in the progression of renal damage. The natural polyphenol naringenin is known to exert potent antioxidant and anti-inflammatory effects. In this study, we have investigated the effect of naringenin on kidney dysfunction, fibrosis, endoplasmic reticulum (ER) stress, angiotensin II type I receptor (AT1R) expression and inflammation in daunorubicin (DNR) induced nephrotoxicity model. Nephrotoxicity was induced in rats by intravenous injection of DNR at a cumulative dose of 9 mg/kg. After 1 week, naringenin (20 mg/kg/day. p.o) was administered daily for 6 weeks. Biochemical studies were performed to evaluate renal function. Western blotting was performed to measure the protein levels of AT1R, endothelin (ET)1, ET receptor type A (ETAR), extracellular signal-regulated kinase (ERK)1/2, nuclear factor (NF)κB p65, peroxisome proliferator activated receptor (PPAR)γ, oxidative/ER stress, apoptosis, and inflammatory markers in the kidney of DNR treated rats. Histopathological analysis was done using hemotoxylin eosin and Masson trichrome stained renal sections to investigate the structural abnormalities and fibrosis. DNR treated rats suffered from nephrotoxicity as evidenced by worsened renal function, increased blood urea nitrogen, serum creatinine levels in renal tissues and histopathogical abnormalities. Treatment with naringenin mitigated these changes. Furthermore, naringenin up regulated PPARγ and down regulated AT1R, ET1, ETAR, p-ERK1/2, p-NFκB p65, ER stress, apoptosis, and inflammatory markers. Our results suggest that naringenin has an ability to improve renal function and attenuates AT1R, ERK1/2-NFκB p65 signaling pathway in DNR induced nephrotoxicity in rats.

Original languageEnglish (US)
Pages (from-to)154-159
Number of pages6
JournalInternational Immunopharmacology
Volume28
Issue number1
DOIs
StatePublished - Jun 12 2015

Keywords

  • Angiotensin II type I receptor
  • Endoplasmic reticulum stress
  • Extracellular signal-regulated kinase
  • Inflammation
  • Nephrotoxicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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