The Experimental Study Of Glomerular Injury Induced By Xylitol In Diabetes Rats

Background: Xylitol, which can ameliorate glucose metabolism and improveinsulin secretion, is widely used for sweeting agent for diabetic patients.Exogenous xylitol could increase the level ofserum uric acid, which wouldinduce and/or aggravate renal lesions. Diabetic nephropathy(DN) is oneof the commonest diabetic microvascular complications, which is the majorcause of disabilities and short life expectancy in patients with diabetesmellitus(DM). The pathological hallmark of DN is kidney-megaly, excessiveaccumulation of extracellular matrix(ECM) in kidney, glomerular basementmembrane(GBM) and tubular basement membrane(TBM) thickening, whichinduce glomerular sclerosis, tubulointerstitial fibrosis and subse-quently proteinuria, hypertension, chronic renal insufficiency. TypeⅣcollagen(Col-Ⅳ) is thought to be the major collagenous component of GBMand ECM. And the deposition of Col-Ⅳis the pathogenic basement of DN.In this study DN rats model was established by streptozotocin(STZ), andthen feed by different percentage xylitol storage. The serum/urineconcentration of uric acid, allantoin, creatinine and expression of Col-Ⅳin glomeruli were detected. We aim to observe the effect of dietary xylitolsupplementation on the uric acid metabolism and DN.Objective: To observe the effect of dietary xylitol supplementation onthe uric acid metabolism and DN.Methods: 1. The concentration of uric acid, allantoin and creatinine wasdeterminated by reversed-phage high performance liquid chromatography(RP-HPLC) simultaneously. 2. 16 of 100 male Wistar rats were randomlytaken out as normal control group(n=16, NC group). The other 84 rats servedas diabetes model were induced by intravenous injection of STZ at the doseof 50 mg/kg. 80 rats were taken out and divided into 4 groups: diabetesrats(n=20, DC group), diabetes rats received 5％dietary xylitol supplementation (n=20, D+5％Xy group), diabetes rats received 10％dietaryxylitol supplementation(n=20, D+10％Xy group), diabetes rats received 20％dietary xylitol supplementation(n=20, D+20％Xy group). At the end of 4weeks and 8 weeks after treatment, the concentration of uric acid,allantoin and creatinine in serum/urine of half rats in each groups weretested. The rats were sacrificed, and the expression of Col-Ⅳinglomeruli were determination. All the results were analyzed with SPSS.Results: 1. The concentration of uric acid, allantoinand creatininewasdetected by RP-HPLC simultaneously. Good linearity was observed in therange of 5-1000μmol/L, r=0.999. The intra-and inter-assay coefficientsof variation were both below 7％. The average recovery rates of threesubstance was between 96.1％and 102.9％. 2. At the end of 4 and 8 weeks,the body weight were lighter and the blood glucose were higher of alldiabetes groups than NC group (P＜0.05). Compared to the group DC, threegroups received dietary xylitol supplementation have higher body weightand lower blood glucose, but only the difference between the D+20％Xy groupand DC group was significant (P＜0.05). 3. At the end of 4 and 8 weeks,the kidney weight index(kiney weight/body weight) of all diabetes groupswere higher than NC group (P＜0.05). Compared to the group DC, D+20％Xygroup had lower kidney weight index (P＜0.05). 4. The concentration ofserum uric acid and allantoin both increased in the diabetes groupscompared to NC group. The level of urine uric acid and allantoin decreasedin the diabetes groups, either. D+5％Xy and D+10％Xy groups had higherconcentration of serum uric acid, allantoin as well as lower urine uricacid and allantoin. Whereas, D+20％Xy group had lower concentration ofserum uric acid and allantoin and higher urine uric acid and allantoin(P＜0.05). 5. The concentration of serum creatinine,urine creatinineand clearance of creatinine had no significient variance among the fivegroups. 6. The fractional excretion of uric acid(FEUA) of all diabetes groups were lower than NC group. Compared to DC group, FEUA of D+5％Xy andD+10％Xy groups were lower and 20％was higher(P＜0.05). 7. The expressionof Col-Ⅳin glomrruli were up-regulated in all diabetes groups at theend of 4 and 8 weeks. Compared to DC groups, the expression of Col-Ⅳweresignificantly increased in D+5％Xy and D+10％Xy group, and decreased inD+20％Xy group(P＜0.05).Conclusions: 1. The RP-HPLC can detect the concentration of uric acid,creatinine and aIlantoin in little sample, and is well accurate, simpleand quick, can be used in study and clinical laboratory. 2. The diabetesrat model induced by STZ have the typically clinical characters.Significant kidney lesion was found at the end of 4 weeks. So it can beuse for DN model. 3. The synthesis and clearance of uric acid and a]lantoinboth increased in the DC group rat compared with the NC group, however,the synthesis increased more significantly. So the concentration of uricacid increased. 4. Low and mediate dose of dietary xylitol supplementationcould make the synthesis of purine metabo]ites increased and clearancedecreased, and subsequently raise the level of serum uric acid anddeposition of Col-Ⅳin glomeruli. DN would be worsen. 5. High dose ofxylitol can ameliorate the tubular injury of DM rats, with the uric acidclearance increasing and the level of serum uric acid decreasing, as wellas the expression of Col-Ⅳin giomeruli down-regulated. The injuries tothe kidney could be protected.