title: Metformin Prevents Renal Stone Formation through an Antioxidant Mechanism In Vitro and In Vivo.
abstract: Oxidative stress is a causal factor and key promoter of urolithiasis associated with renal tubular epithelium cell injury. The present study was designed to investigate the preventive effects of metformin on renal tubular cell injury induced by oxalate and stone formation in a hyperoxaluric rat model. MTT assays were carried out to determine the protection of metformin from oxalate-induced cytotoxicity. The intracellular superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in vitro. Male Sprague-Dawley rats were divided into control group, ethylene glycol (EG) treated group, and EG + metformin treated group. Oxidative stress and crystal formations were evaluated in renal tissues after 8-week treatment. Metformin significantly inhibited the decrease of the viability in MDCK cells and HK-2 cells induced by oxalate. Besides, metformin markedly prevented the increased concentration of MDA and the decreased tendency of SOD in oxalate-induced MDCK cells and HK-2 cells. In vivo, the increased MDA levels and the reduction of SOD activity were detected in the EG treated group compared with controls, while these parameters reversed in the EG + metformin treated group. Kidney crystal formation in the EG + metformin treated group was decreased significantly compared with the EG treated group. Metformin suppressed urinary crystal deposit formation through renal tubular cell protection and antioxidative effects.
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Xiong
authors: 0000-0001-7625-8786
authors: X
authors: Yang
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Hao
authors: H
authors: Ding
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Zhenbang
authors: Z
authors: Qin
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Changwen
authors: C
authors: Zhang
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Shiyong
authors: S
authors: Qi
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Hongtuan
authors: 0000-0003-2230-3195
authors: H
authors: Zhang
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Tong
authors: T
authors: Yang
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Zhen
authors: Z
authors: He
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Kuo
authors: K
authors: Yang
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: E
authors: 0000-0001-6569-7038
authors: E
authors: Du
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Chunyu
authors: C
authors: Liu
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Yong
authors: 0000-0001-8943-1023
authors: Y
authors: Xu
authors: Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, China.
authors: Zhihong
authors: 0000-0002-5416-8779
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D019855:Ethylene Glycol; D006801:Humans; D007669:Kidney Calculi / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control* / Q000652:urine; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D010070:Oxalates; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010070:Oxalates; D008315:Malondialdehyde; D008687:Metformin; D013482:Superoxide Dismutase; D019855:Ethylene Glycol