title: Mefunidone attenuates tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction.
abstract: BACKGROUND
  Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages.
  
  
  RESULTS
  Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3.
  
  
  CONCLUSIONS
  Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation.
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathology, Hunan University of Chinese Medicine, Changsha, Hunan, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Mei
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Qiongjing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhangzhe
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Respiration, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Huixiang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Lv
authors.affiliation: Department of Medical Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China.
authors.forename: Gaoyun
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China; State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: C000607330:1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one; D005353:Fibronectins; D016328:NF-kappa B; D010879:Piperazines; D011728:Pyridones; D050796:STAT3 Transcription Factor; D053773:Transforming Growth Factor beta1; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases