title: Anti-nephrolithic potential of resveratrol via inhibition of ROS, MCP-1, hyaluronan and osteopontin in vitro and in vivo.
abstract: BACKGROUND
  Though resveratrol is known to have anti-cancer, anti-diabetic, anti-oxidant and anti-inflammatory activities, the inhibitory mechanism of resveratrol in kidney stone formation has not been elucidated so far.
  
  
  METHODS
  ELISA, flow cytometry, RT-PCR, and western blotting were performed. Human renal epithelial cells (HRCs) and rats with ethylene glycol (EG)-induced kidney stones were used.
  
  
  RESULTS
  A wound healing assay revealed that resveratrol significantly inhibited the oxalate-mediated migration of HRCs, considering oxalate mediates kidney stone formation. Also, resveratrol suppressed the mRNA expression of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunits such as p22(phox) and p47(phox), monocyte chemoattractant protein 1 (MCP-1) and osteopontin (OPN) in oxalate-treated HRCs. Furthermore, western blotting showed that resveratrol downregulated the expression of MCP-1-related proteins including transforming growth factor(TGF-β1), TGFR-I or II and hyaluronan in oxalate-treated HRCs. Consistently, resveratrol reduced oxalate-mediated production of reactive oxygen species (ROS) and malondialdehyde (MDA) in oxalate-treated HRCs, while the activities of anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were enhanced by resveratrol in HRCs and EG-treated kidneys of rats. Consistently, resveratrol significantly reduced the number of urine calcium oxalate crystals and serum MDA, and attenuated the expression of OPN and hyaluroran in EG-treated rats.
  
  
  CONCLUSIONS
  Our findings suggest that resveratrol exerts anti-nephrolithic potential via inhibition of ROS, MCP-1 hyaluronan and OPN signaling.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. sungkim7@khu.ac.kr.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Hong
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Hyun-Suk
authors.initials: HS
authors.lastname: Ko
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.forename: Kyoo Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D002129:Calcium Oxalate / Q000652:urine; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D019855:Ethylene Glycol; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007669:Kidney Calculi / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D009249:NADP / Q000096:biosynthesis; D019255:NADPH Oxidases / Q000096:biosynthesis; D053495:Osteopontin / Q000096:biosynthesis*; D019815:Oxalic Acid / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015291:Transforming Growth Factors / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000975:Antioxidants; D018932:Chemokine CCL2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D053495:Osteopontin; D002129:Calcium Oxalate; D008315:Malondialdehyde; D009249:NADP; D015291:Transforming Growth Factors; D006820:Hyaluronic Acid; D019815:Oxalic Acid; D019255:NADPH Oxidases; D019855:Ethylene Glycol; D000077185:Resveratrol