TY - JOUR
T1 - Curcumin alleviates renal dysfunction and suppresses inflammation by shifting from M1 to M2 macrophage polarization in daunorubicin induced nephrotoxicity in rats
AU - Karuppagounder, Vengadeshprabhu
AU - Arumugam, Somasundaram
AU - Thandavarayan, Rajarajan A.
AU - Sreedhar, Remya
AU - Giridharan, Vijayasree V.
AU - Afrin, Rejina
AU - Harima, Meilei
AU - Miyashita, Shizuki
AU - Hara, Masanori
AU - Suzuki, Kenji
AU - Nakamura, Masahiko
AU - Ueno, Kazuyuki
AU - Watanabe, Kenichi
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Numbers 23602012 , 26460239 .
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9 mg/kg DNR (i.v). Followed by curcumin (100 mg/kg) administration orally every day for 6 weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)κB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats.
AB - The molecular mechanism of curcumin in macrophage polarization remains unknown in renal failure. We examined, whether curcumin treatment is associated with the modulation of renal function and macrophage phenotype switch in daunorubicin (DNR) induced nephrotoxicity model. Sprague-Dawley rats were treated with a cumulative dose of 9 mg/kg DNR (i.v). Followed by curcumin (100 mg/kg) administration orally every day for 6 weeks. DNR treated rats showed nephrotoxicity as evidenced by worsening renal function, which was assessed by measuring creatinine and blood urea nitrogen in serum. These changes were reversed by treatment with curcumin, which resulted in significant improvement in renal function. Furthermore, curcumin increased cluster of differentiation (CD)163 expression, and down-regulated renal expression of antigen II type I receptor (AT1R), endothelin (ET)1, ET receptor type A and B (ETAR and ETBR), CD68 and CD80. Renal protein expression of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)κB p65 were increased in DNR treated rats, and treatment with curcumin attenuated these increased expression. Curcumin mediated a further increase in the levels of interleukin (IL)-10. In addition, the expression of M1 phenotype was increased in DNR treated rats, which were attenuated by curcumin. Taken together, our results demonstrated that polyphenol curcumin has an ability to improve renal function and might induce the phenotypic switching from M1 to M2 macrophage polarization in DNR induced nephrotoxicity in rats.
KW - Cluster of differentiation 163
KW - Curcumin
KW - Cytokine
KW - Macrophage
KW - Nuclear factor kappa B
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U2 - 10.1016/j.cyto.2016.05.001
DO - 10.1016/j.cyto.2016.05.001
M3 - Article
C2 - 27203664
AN - SCOPUS:84969142676
SN - 1043-4666
VL - 84
SP - 1
EP - 9
JO - Cytokine
JF - Cytokine
ER -