Establishment Of The High Uric Acid Model In C.elegans

At present,the wordwide used models of hyperuricemia exist many defects,which greatly limitis the treatment and development of hyperuricemia.The nematode Caenorhabdizis elgans(C.elegans)which is similar to human on the uric acid metabolism is used to establish the high uric acid model.This paper provided a reliable model of screening drug for treatment of hyperuricemia to overcome the deficiency of the existing model.In this paper,we adopted to treat C.elegans with uric acid and the precursors,determine the changes of uric acid with the high performance liquid chromatography(HPLC)and the lifespan for selecting the appropriate concentration and the suitable modeling time.Morever,we dicuss the stability and the curability and the oxidative damage of the high uric acid model in C.elegans through the determination of the activity of catalase(CAT)and superoxide dismutase(SOD)and the influence of free radicals.Besides,we revealed the modeling mechanism in C.elegans through the activity of xanthine oxidase(XOD),Results are as follows:The uric acid levels of the C.elegans is 27.91 μg/500 worms.These four precursors such as hypoxanthine(HX),adenine(A),xanthine(XH),uric acid(UA)were treated to 500 worms with different concentrations(0.05,0.15,0.25 mg/mL)for 24 h respectively.There was a statistically significant increase in the uric acid level with xanthine and uric acid(0.25 mg/mL,p<0.001)and a significant increase with hypoxanthine(0.25 mg/mL,p<0.05).But xanthine(0.25 mg/mL)is the most in elevating the uric acid in C.elegans about 18.51μg/500 worms(64.76%increase).At the optimum concentrations,these four precursors such as hypoxanthine,adenine,xanthine,uric acid were given to the C.elegans with different time(8 h,12 h,18 h,24 h,32 h)with 500 worms respectively.There was a statistically significant increase in the uric acid level(p<0.001)and a lower drug damage(p>0.05)after giving the xanthine(0.25 mg/mL,18 h).So we chose xanthine(0.25 mg/mL,18 h)to establish the high uric acid model in C.elegans.Morever,the model was proved to keep a high uric acid level for up to 12 h.Furthermore,after given allopurinol(0.25 mg/mL,12 h),the uric acid of hyperuricemic C.elegans had a significant reduction by 15%.The brood size、life span、head thrashes and body bend all was no significant difference with the normal control group.Finally,xanthine oxidase activity in model C.elegans showed a significant increase(p<0.001),which resulted in a raised uric acid content.But there was no significant changes(p>0.05)of the activity of catalase(CAT),superoxide dismutase(SOD).In addition,the fluorescence experiments showed that reactive oxygen free radical of models worms were no significant change compared with the normal control worms.These results showed that the C.elegans of high uric acid model was not injured by building agent of xanthine.In conclusion,this work suggested that one high uric acid model with low drug damage,as well as high efficiency and stability,was established in C.elegans.