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

• Published in: Pharmacological reports Vol. 65; no. 4; pp. 970 - 979
• Main Authors: Hyuk Hong, Sang, Lee, Hyo-Jung, Jung Sohn, Eun, Ko, Hyun-Suk, Sang Shim, Bum, Seok Ahn, Kyoo, Kim, Sung-Hoon
• Format: Journal Article
• Language: English
• Published: Cham Elsevier B.V 2013; Springer International Publishing
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - therapeutic use; Calcium Oxalate - urine; Cell Movement - drug effects; Cell Survival - drug effects; Cells, Cultured; Chemokine CCL2 - biosynthesis; Down-Regulation - drug effects; Drug Safety and Pharmacovigilance; Ethylene Glycol; Humans; hyaluronan; Hyaluronic Acid - biosynthesis; Kidney - drug effects; Kidney - metabolism; Kidney Calculi - chemically induced; Kidney Calculi - drug therapy; Male; Malondialdehyde - blood; Malondialdehyde - metabolism; MCP-1; NADP - biosynthesis; NADPH Oxidases - biosynthesis; OPN; Osteopontin - biosynthesis; oxalate; Oxalic Acid - pharmacology; Pharmacotherapy; Pharmacy; Rats; Reactive Oxygen Species - metabolism; Resveratrol; ROS; Stilbenes - pharmacology; Stilbenes - therapeutic use; Transforming Growth Factors - biosynthesis; Wound Healing - drug effects; MCP-1; oxalate; OPN; resveratrol; hyaluronan; ROS
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/S1734-1140(13)71078-8

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. 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. 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 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-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 MD A, and attenuated the expression of OPN and hyaluroran in EG-treated rats. Our findings suggest that resveratrol exerts anti-nephrolithic potential via inhibition of ROS, MCP-1 hyaluronan and OPN signaling.