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

Sang Hyuk Hong, Hyo-Jung Lee, Eun Jung Sohn, Hyun-Suk Ko, Bum Sang Shim, Kyoo Seok Ahn, Sung-Hoon Kim
2013 Pharmacological Reports  
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: A wound healing assay revealed that resveratrol significantly inhibited the oxalate-mediated
more » ... 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-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.
doi:10.1016/s1734-1140(13)71078-8 pmid:24145091 fatcat:vg2xrj2w5bhlrns2siqbw5leai