Effect of dimethyl fumarate on the renal calcium oxalate stone formation in rats and possible mechanism

Objective To observe the effect of dimethyl fumarate (DMF) on the renal calcium oxalate crystals formation in SD rats induced by glyoxylic acid monohydrate, and explore the possible mechanism. Methods Thirty male Sprague-Dawley rats were randomly divided into 3 groups: control group, model group and DMF group (n=10 each). The control group was free to drink purified water. Model group was induced by intraperitoneal injection of glyoxylic acid monohydrate to establish a kidney calcium oxalate stone model, and DMF group was treat with DMF by gastric administration on the basis of modeling. After 10 days of continuous treatment, the 24 h urine, serum and kidney of rats in each group were collected. Serum creatinine (SCr) value, calcium and oxalate (Ox) contents in urine were measured. Von Kossa staining method was used to detect the deposition of calcium oxalate crystals in kidney tissue. Western blotting was used to detect the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 protein in renal tissue. The frozen section DHE staining was used to detect the ROS level in the kidney, thiobarbituric acid method was used to test malondialdehyde (MDA) content, and the xanthine oxidase method was used to detect superoxide dismutase (SOD) activity. Results There was no visible calcium crystal in the kidney of the control group. Compared to the model group, the amounts of renal calcium crystal were significantly reduced in the DMF group (76.07±4.87) /HP vs. (37.94±4.63) /HP (t=17.940, P 0.05). There was no significant difference in 24-hour urinary calcium ion content between the three groups (F=1.670, P>0.05). Compared with the control group, renal ROS levels (t=20.920, P<0.01), Nrf2 (t=17.290, P<0.01) and HO-1 protein (t=38.030, P<0.01) expression levels were significantly increased in the model group. Compared with the model group, renal ROS levels were significantly reduced in the DMF group (t=16.000, P<0.01), while the expression levels of Nrf2 (t=25.580, P<0.01) and HO-1 protein (t=79.290, P<0.01) were significantly increased. Conclusion The formation of calcium oxalate kidney stones is related to oxalate-mediated oxidative stress. DMF may interfere with the pathogenesis of calcium oxalate kidney stones by activating Nrf2 to induce HO-1 to inhibit oxidative stress. Key words: Calcium oxalate stones; Oxidative stress; Nuclear factor erythroid 2-related factor 2; Dimethyl fumarate