TY - JOUR
T1 - Naringenin ameliorates daunorubicin induced nephrotoxicity by mitigating AT1R, ERK1/2-NFκB p65 mediated inflammation
AU - Karuppagounder, Vengadeshprabhu
AU - Arumugam, Somasundaram
AU - Thandavarayan, Rajarajan Amirthalingam
AU - Pitchaimani, Vigneshwaran
AU - Sreedhar, Remya
AU - Afrin, Rejina
AU - Harima, Meilei
AU - Suzuki, Hiroshi
AU - Suzuki, Kenji
AU - Nakamura, Masahiko
AU - Ueno, Kazuyuki
AU - Watanabe, Kenichi
N1 - Funding Information:
This research was supported by the Ministry of Education, Culture, Sports and Technology of Japan ( 23602012 ) and by a grant from the Promotion and Mutual Aid Corporation for Private Schools, Japan ( 26460239 ).
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/6/12
Y1 - 2015/6/12
N2 - 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.
AB - 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.
KW - Angiotensin II type I receptor
KW - Endoplasmic reticulum stress
KW - Extracellular signal-regulated kinase
KW - Inflammation
KW - Nephrotoxicity
UR - http://www.scopus.com/inward/record.url?scp=84930938257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930938257&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2015.05.050
DO - 10.1016/j.intimp.2015.05.050
M3 - Article
C2 - 26072060
AN - SCOPUS:84930938257
SN - 1567-5769
VL - 28
SP - 154
EP - 159
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 1
ER -