title: Curcumin alleviates renal dysfunction and suppresses inflammation by shifting from M1 to M2 macrophage polarization in daunorubicin induced nephrotoxicity in rats.
abstract: 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 9mg/kg DNR (i.v). Followed by curcumin (100mg/kg) administration orally every day for 6weeks. 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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Remya
authors.initials: R
authors.lastname: Sreedhar
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, Houston, TX 77054, USA.
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Rejina
authors.initials: R
authors.lastname: Afrin
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Shizuki
authors.initials: S
authors.lastname: Miyashita
authors.affiliation: Niigata Prefectural Yoshida Hospital, 32-14 Daibo-cho, Yoshida, Tsubame City 956-0242, Niigata, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi Kofu, Yamanashi 400-8506, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address: watanabe@nupals.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003474:Curcumin / Q000494:pharmacology*; D003630:Daunorubicin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism
chemical_list: D060149:Tetraspanin 30; D016753:Interleukin-10; D003404:Creatinine; D003474:Curcumin; D003630:Daunorubicin
keywords: Cluster of differentiation 163; Curcumin; Cytokine; Macrophage; Nuclear factor kappa B