Anti-nephrolithic potential of resveratrol via inhibition of ROS,MCP-1,hyaluronan and osteopontin in vitro and in vivo

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. method: 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: awound healing assay revealed that resveratrol significantly inhibited the oxalate-mediated migration of hrcs,considering oxalate mediates kidney stone formation. also,resveratrol suppressed the mrnaexpression of nicotinamide adenine dinucleotide phosphate hydrogen (nadph) oxidase subunits such as p22phox and p47phox,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-b1),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.