ABSTRACT
The aim of this study was to establish an efficient and stable mouse model of hyperuricemic nephropathy (HN) by testing different modes of administration of potassium oxonate (PO) combined with hypoxanthine (Hx). Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guangdong Pharmaceutical University. Male C57BL/6 mice were randomly divided into a control group, a PO+Hx group (i.g.; 100 mg·kg-1·d-1 and 500 mg·kg-1·d-1, respectively), and a PO+Hx group (i.p.; 100 mg·kg-1·d-1, and 500 mg·kg-1·d-1). This HN model was induced by combination of PO and Hx administration once daily for 21 days. The results of serum biochemistry showed that the levels of serum creatinine and 24 h albuminuria were increased compared with the normal group in intragastric administration of PO combined with Hx (P < 0.05), but there was no significant difference in serum uric acid and hepatic levels of xanthine oxidase. The maximum value of serum uric acid and creatinine was 349.3 μmol·L-1 and 26.4 μmol·L-1, respectively, in mice injected with PO combined with Hx. The levels of liver xanthine oxidase and 24 h albuminuria were significantly increased in mice injected with PO combined with Hx (P < 0.01). Pathological data showed that renal tubules were dilated, the epithelial cells of renal tubules were disordered, and the production of collagen fibers, reactive oxygen species (ROS) and lipid peroxidase 4-hydroxynonenal (4-HNE) were slightly increased after intragastric administration of PO combined with Hx mice. Obvious infiltration of inflammatory cells and large area of collagen deposition, with a large amount of ROS and the lipid peroxide 4-HNE were produced in mice injected with PO combined with Hx. Western blot analysis showed that the expression of fibronectin (FN) and urate transporter 1 (URAT1) was increased after intragastric administration of PO combined with Hx in mice and further increased in mice injected with PO combined with Hx. This study demonstrates that injection with 100 mg·kg-1 potassium oxonate combined with 500 mg·kg-1 hypoxanthine establishes a stable and efficient mouse HN model.
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OBJECTIVE@#The present study is to determine the potential treatment effects of ethyl acetate fraction of Tephrosia purpurea Linn. leaves (EATP) against gout.@*METHODS@#Gout in experimental rats was induced with potassium oxonate at the dose of 250 mg/kg (intraperitoneal injection) for 7 consecutive days; EATP was administered 1 h after administration of the potassium oxonate on each day of experiment. Potassium oxonate was discontinued on the 8th day; thereafter allopurinol (10 mg/kg, p.o.) and EATP (200 and 400 mg/kg, p.o.) were continued until day 14. The uric acid level was measured from serum and urine during the experiment. Other biochemical parameters were assessed, including blood and urine creatinine, erythrocyte sedimentation rate, and total protein. Blood urea nitrogen, serum aspartate aminotransferase serum alanine aminotransferase and alkaline phosphatase were also measured. The blood was analyzed for levels of malondialdehyde and the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Histopathological and radiological changes in the ankle of rats were observed after completion of the experiment.@*RESULTS@#EATP was able to decrease serum uric acid and creatinine level; it also reduced inflammation, oxidative stress and lysosomal enzyme level, which has a role in acute inflammation. EATP increased uric acid excretion through urine due to its uricosuric effect.@*CONCLUSION@#EATP lowered the serum uric acid level and increased the urine uric acid level through excretion, which is useful in the treatment of gout. Hence the EATP was found to be helpful in the treatment of gout.
ABSTRACT
To study what kind of role uric acid play on the relationship between oxidative Stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats. Twenty-six eight male Wistar rats were divided into two groups randomly. Potassium oxonate was used to establish hyperuricemic model for four weeks. In 2nd and 4th week, uric acid (UA) level, total superoxide dismutase (T-SOD), Gu,Zn-SOD activity and interleukin-1beta (IL-1ß) concentration in serum were determined respectively. In 4th week, one hour after last PO treatment, five rats of every group were given Evans Blue to test blood-brain barrier (BBB) permeability. Other brains were obtained to analysis T-SOD, Gu,Zn-SOD activity and IL-1ß concentration in cerebral system. Meanwhile, brain and kidney were stained with hematoxylin and eosin (H&E) to observe pathological change. In 2nd week, both of T-SOD and Gu,Zn-SOD activity in serum increased obviously (P<0.05) in hyperuricemia rats. However, IL-1ß content didn't change remarkably. In the 4th week, T-SOD activity in model group had become similar with control group, and at the same time IL-1ß content in serum increased significantly (P<0.05). Pathological section showed the structural and functional unit of the kidney had been damaged. On the contrary, both of T-SOD and Gu,Zn-SOD activity in brain increased obviously (P<0.05), but IL-1ß concentration was no significant difference between two groups. In addition, the results of Evans Blue and H&E suggested the integrity of BBB and structure of brain were not changed after PO treatment. The permeability of BBB and form of UA would be potential factors to decide what kind role UA play on keeping balance between anti-oxidative stress and induction of inflammatory response.
Subject(s)
Animals , Male , Rats , Oxidative Stress , Hyperuricemia/pathology , Uric Acid/analysis , Peripheral Nervous System/injuriesABSTRACT
Objective To explore a reliable method to establish a rat model of hyperuricemia associated with abnormal uric acid excretion, and to lay the foundation for the study of pathogenesis of uric acid excretion disorder and the optimization of the treatment plan.Methods The models were established respectively by potasium oxonate(300 mg/kg) with pyrazinamide (300 mg/kg) or ethambutol(250 mg/kg).Continuous dosing for 1, 3 and 5 weeks, to determine the content of uric acid in rat blood, urine, and stool, the function of liver and kidney was detected and pathological examination was performed.Results The blood uric acid in the potasium oxonate and ethambutol group was increased first and then decreased, while in the potasium oxonate and pyrazinamide group were increased steadily and the excretion of uric acid in urine was stable during the continuous administration.The two methods showed no harmful effect on the liver and kidney function.Conclusions A stable rat model of hyperuricemia associated with uric acid excretion disorder can be effectively established by potassium oxonate and pyrazinamide, exhibiting similar manifestations of clinical hyperuricemia and uric acid excretion disorder.
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Objective:To discuss the influence of Tongfengning Capsule (TFN) in the levels of uricacid (UC),creatinine (Cr) and urea nitrogen (BUN) in mouse serum and the activities of the xanthine oxidase (XOD),adenosine deaminase (ADA) activity in the liver homogenate of the mice with hyperuricemia,and to observe the improvement effect of TFN on the pathological changes of liver tissue and to clarify its mechanisms.Methods:The models of mouse hyperuricemia were induced by yeast extract with potassium oxonate.Seventy mice were divided into blank control group,model group,low (200 mg · kg 1),medium (400 mg · kg-1) and high (800 mg · kg-1) doses of TFN groups,allopurinol positive drug control group (50 mg · kg-1),Tongfengshu (TFS,600 mg · kg-1) positive drug control group (n=10).The levels of UC,Cr,BUN in serum and the activities of XOD,ADA in homoggenate were detected and the histopathological changes of the kidney tissue of the mice were measured with HE staining.Results:Compared with blank control group,the levels of serum UC,Cr and BUN ofthe mice in model group were significantlyincreased (P＜0.01),and the activities of XOD and ADA in liver tissue were also increased (P＜0.01).Compared with model group,the levels of serum UC,Cr and BUN of the mice in positive drug control groups and different doses of TFN groups were decreased (P＜0.01),and the activities of XOD and ADA in liver tissue were also decreased (P＜0.05),especially in high dose of TFN group.Compared with model group,the pathologic changes such as renal glomerulus atrophy,renal interstitial fibrosis and expansion of renal tubule of the mice in positive drug control groups and high dose of TFN group were improved to a certain extent.Conclusion:TFN has improvement effcet on the hyperuricemia in the mice and its mechanism is related to the inhibition of uricogenesis and the promotion of UC excretion.
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Objective:To discuss the influence of Tongfengning Capsule (TFN) in the levels of uricacid (UC),creatinine (Cr) and urea nitrogen (BUN) in mouse serum and the activities of the xanthine oxidase (XOD),adenosine deaminase (ADA) activity in the liver homogenate of the mice with hyperuricemia,and to observe the improvement effect of TFN on the pathological changes of liver tissue and to clarify its mechanisms.Methods:The models of mouse hyperuricemia were induced by yeast extract with potassium oxonate.Seventy mice were divided into blank control group,model group,low (200 mg · kg 1),medium (400 mg · kg-1) and high (800 mg · kg-1) doses of TFN groups,allopurinol positive drug control group (50 mg · kg-1),Tongfengshu (TFS,600 mg · kg-1) positive drug control group (n=10).The levels of UC,Cr,BUN in serum and the activities of XOD,ADA in homoggenate were detected and the histopathological changes of the kidney tissue of the mice were measured with HE staining.Results:Compared with blank control group,the levels of serum UC,Cr and BUN ofthe mice in model group were significantlyincreased (P＜0.01),and the activities of XOD and ADA in liver tissue were also increased (P＜0.01).Compared with model group,the levels of serum UC,Cr and BUN of the mice in positive drug control groups and different doses of TFN groups were decreased (P＜0.01),and the activities of XOD and ADA in liver tissue were also decreased (P＜0.05),especially in high dose of TFN group.Compared with model group,the pathologic changes such as renal glomerulus atrophy,renal interstitial fibrosis and expansion of renal tubule of the mice in positive drug control groups and high dose of TFN group were improved to a certain extent.Conclusion:TFN has improvement effcet on the hyperuricemia in the mice and its mechanism is related to the inhibition of uricogenesis and the promotion of UC excretion.
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Objective To explore the anti-hyperuricemia activity of bergenin in the model of hyperuricemic mice induced by potassium oxonate. Methods 60 Kunming male mice were divided randomly into six groups, which were normal control group;hyperuricemic model group;and hyperuricemic groups with 20 , 40 , 60 mg/kg berge-nin, and 5 mg/kg allopurinol. Mice were orally administered once daily with 250 mg/kg potassium oxonate for 7 continuous days to create the model, and then three doses of bergenin and allopurinol were orally initiated on the day 1 h after potassium oxonate was given, separately. Serum uric acid, creatinine and urea nitrogon levels, as well as urinary uric acid and creatinine levels were measured. mRNA and protein expression levels of mouse kidney u-rate transporter 1(URAT1), and glucose transporter 9(GLUT9) were also determined. Results Compared with hyperuricemic model group, bergenin significantly reduced serum uric acid, creatinine and urea nitrogon levels, in-creased 24 h uric acid and creatinine excretion, and fractional excretion of uric acid in hyperuricemic mice;mRNA and protein levels of mURAT1 and mGLUT9 were also markedly down-regulated. Conclusion Anti-hyperuricemia effect of bergenin is attributed to the enhancement of uric acid excretion and reversion of mouse urate transporters o-ver-expression.