ABSTRACT
Objective To investigate the mechanism of melamine-induced renal damage in rats.Methods 48 male SD rats were randomly divided into 4 groups with 12 in each group and feed for 3 months.Group A were the control group,feed with standard granule feedstuff and drinking tap water.Group B were stone-induced group,feed with granule feedstuff containing 3％ Mel and drinking tap water.Group C were feed with granule feedstuff containing 3％ Mel and drinking water containing 2％ taurine.Group D were feed with standard granule feedstuff and drinking water containing 2％ taurine.Every week 24 h urine was collected to test PH,SCr,uric acid,protein,8-IP,H2O2 and Mel level.All rats were sacrificed at the end of 3 months.Blood creatinine detection,renal pathology analysis ( HE and Oil ep-red O dyeing,immunohistochemical) and mitochondria separation and detection were undertaken. ResultsMel was not detedted in urine of Group A and Group D.The urine concentration of Mel in Group B and Group C in 1 week,2 weeks,3 weeks,4 weeks were 3.16 ±0.45,4.39 ±0.213,5.40 ±0.28,5.50 ±3.26 and 3.52 ±0.49,4.32 ± 0.135,5.34 ± 0.40,5.46 ± 2.99 mg/ml,respectively.Compared with Group A,the Mel concentration in urine of Group B and C were drug exposure time dependent.In Group A,the urine protein,urine creatinine clearance,serum creatinine,and renal/weight ratio were 6.45 ± 1.45 mg/24 h,28.0 ± 7.4mmol/l,0.56 ±0.03 ml · min-1 · 100g-1,2.29 ±0.89 mg/g,while in Group B and C,the urinary protein urine,serum creatinine,creatinine clearance,kidney/weight ratio were 14.56 ± 7.69,56.8 ± 5.2,0.29 ±0.05,4.16 ±0.27 and 16.44 ±6.29,55.8 ±7.4,0.30 ±0.07,4.40 ±0.56,respectively.Compared with group A,in Group B and C,the urinary protein increased significantly,urine creatinine clearance reduced,serum creatinine reduced,and renal/weight ratio increased.Compared with Group B,the improvement of renal function in Group C was not significant,and the decrease of serum creatinine and urinary protein were not obvious (P ＞ 0.05).In Group B and C,the urine H2O2,8-IP and mitochondrial oxidatie detection reagent SOD,GSH-PX numerical were 28.5 ± 5.2 mmol/1,3.26 ± 1.6 pg/ml,21.1 ± 7.8 U/mg prot,19.0 ±2.5 energy unit and 26.7 ±4.8 mmol/l,2.99 ±8.5 pg/ml,20.3 ±6.9 U/mg prot,17.9 ±4.8 energy unit,respectively.The difference between Group B and C was not statistically significant (P ＞0.05).Pathological analysis showed Mel was mainly concentrated in crystal tubular lumen (Group B and C),kidney interstitial damage was apparent,and kidney inflammation and fibrosis progressive developed with the increase of the drug exposure time. Conclusions Mel can induce kidney damage and stone formation in rats,and stone was mainly in tubular location in inner medullary zone.It is not the oxidative stress way that Mel leads to kidney damage.