AB261. Metformin prevents renal stone formation through an antioxidant mechanism in vitro and in vivo

Background: 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.

Methods: MTT assays were carried out to determine the protection of metformin in MDCK cells from oxalate-induced cytotoxicity. The intracellular superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured to investigate the antioxidant effect of metformin. We divided male Sprague-Dawley rats into a control group, a 0.75% ethylene glycol (EG) group and a 0.75% ethylene glycol plus 200 mg/kg/day metformin group. Blood and 24-hour urine samples, and kidney sections were collected at the end of 8-week treatment. Oxidative stress was evaluated with SOD activities and MDA levels in renal tissues. Crystal formations were examined using hematoxylin and eosin (HE) staining and polarized light optical microscopy.

Results: Co-exposure to metformin significantly inhibited the decrease of the viability in MDCK cells induced by oxalate. Besides, metformin markly prevented the increased concentration of MDA and the decreased tendency of SOD in oxalate-induced MDCK cells. In vivo, the increased MDA levels and the reduction of SOD activity were detected in EG-induced group compared with controls, while these parameters reversed significantly in the rats co-treated with EG and metformin. Kidney crystal formation in EG plus metformin group was decreased significantly compared with that in EG group.

Conclusions: Metformin suppressed urinary crystal deposit formation through renal tubular cell protection and antioxidative effects.

Keywords: Urolithiasis; antioxidants; rats, Sprague-Dawley; metformin