海带褐藻多糖硫酸酯对腺嘌呤诱导的小鼠高尿酸血症的拮抗作用

本文探讨了海带褐藻多糖硫酸酯(fucoidan from Laminaria japonica,FL)对腺嘌呤诱导的小鼠高尿酸血症的拮抗作用。首先利用腺嘌呤灌胃法建立高尿酸血症动物模型,再以不同剂量(0.100、0.150、0.200 g/kg)的海带褐藻多糖硫酸酯治疗4周,最后对小鼠血清尿酸、肌酐、肝脏匀浆液中腺苷脱氨酶(ADA)和黄嘌呤氧化酶(XOD)的活性及小鼠肾脏组织病理学变化进行检测(HE染色)。结果表明,与空白组相比,腺嘌呤能极显著升高小鼠血清尿酸、肌酐水平、肝脏XOD及ADA活性(P0.01)。与模型组相比,海带褐藻多糖硫酸酯各剂量均能极显著降低小鼠血清尿酸、肌酐水平、肝脏XOD及ADA活性(P0.01)。光镜观察结果显示,与模型组相比,海带褐藻多糖硫酸酯治疗组小鼠的肾损伤有一定程度恢复。综上所述,海带褐藻多糖硫酸酯对腺嘌呤诱导的小鼠高尿酸血症有一定程度的缓解作用。     

几种天然产物对高尿酸血症大鼠血清尿酸水平的影响初探

目的:探讨几种天然产物对高尿酸血症大鼠血清尿酸水平及尿酸排泄的影响.方法:对wistar大鼠灌胃氧嗪酸钾和酵母膏,制作高尿酸血症大鼠动物模型.灌胃给药褐藻糖胶、柠檬酸钾和东哥阿里提取物,2周后采血并进行代谢实验,检测血清尿酸、尿素氮,24小时尿液体积、pH值、尿酸浓度及总量,分析三种活性物质对机体尿酸水平、尿酸排泄、肾脏功能的影响.结果:三种物质均可显著降低高尿酸血症模型大鼠的血清尿酸水平,其中东哥阿里提取物组的24小时排泄尿酸总量较模型组显著降低,褐藻糖胶对实验大鼠的血清尿素氮水平升高有抑制作用.结论:三种活性物质对高尿酸血症大鼠血清尿酸浓度有降低作用,其中褐藻糖胶对肾脏功能有保护作用,从而保证尿酸的顺利排泄,而东哥阿里在降低血尿酸水平的同时,24小时尿液中排泄的尿酸总量也显著低于模型对照组,其机制可能与抑制尿酸生成有关.     

苹果多酚对高尿酸血症大鼠抗氧化能力的影响

目的:高尿酸血症与许多现代慢性疾病关系密切,本文旨在研究苹果多酚对高尿酸血症大鼠体内抗氧化能力的影响.方法:采用对Wistar大鼠灌胃酵母膏及氧嗪酸钾的方法,制作高尿酸血症大鼠模型,再给其灌胃不同剂量苹果多酚.通过测定大鼠血清总抗氧化能力,脂质过氧化产物含量,超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力,探讨苹果多酚对高尿酸血症大鼠机体抗氧化能力的影响.结果:服用苹果多酚的高尿酸血症大鼠的血清总抗氧化能力显著升高,脂质过氧化产物水平相对降低;超氧化物歧化酶是受高尿酸血症和苹果多酚摄入影响最大的抗氧化酶,模型组酶活显著升高,而苹果多酚可以抑制该酶活力因大量尿酸生成引发的升高现象.结论:苹果多酚在适当剂量水平可以显著提高高尿酸血症大鼠的总抗氧化能力,抑制脂质过氧化,同时抑制因大量尿酸生成而引发的超氧化物歧化酶活升高,维护机体氧化还原平衡.     

L-阿拉伯糖对尿酸的调节作用

该文研究了L-阿拉伯糖对正常及高尿酸血症小鼠尿酸的调节作用。在正常小鼠、氧嗪酸钾和次黄嘌呤联合诱导的高尿酸血症小鼠以及氧嗪酸钾和尿酸联合诱导的高尿酸血症小鼠中,通过灌胃给予L-阿拉伯糖:收集尿液,测定尿酸排泄量;取血,测定血清中尿酸、总胆固醇、甘油三酯、血糖、肌酐、尿素氮等常规生化指标;处死小鼠后,取肝、肾、脾,称重,计算脏器指数;取小肠与肝脏,匀浆后测定黄嘌呤氧化酶活性。结果表明:L-阿拉伯糖对正常小鼠,可以增加尿酸排泄,但不能降低血尿酸水平;对氧嗪酸钾和次黄嘌呤联合诱导的高尿酸血症小鼠,对尿酸排泄没有影响,但能升高血尿酸水平;对氧嗪酸钾和尿酸联合诱导的高尿酸血症小鼠,对尿酸排泄及血尿酸水平都没有影响。该研究结果表明L-阿拉伯糖对正常血尿酸水平没有影响,但能升高特定条件下高尿酸血症小鼠的血尿酸水平。     

绞股蓝皂苷对高尿酸血症大鼠血尿酸的影响

高尿酸血症是近年来日益多发的代谢综合征。本研究探讨绞股蓝皂苷提取物对高尿酸血症大鼠血清尿酸的影响及作用方式。研究采用高尿酸血症大鼠动物模型,生化检测,代谢实验方法等,对摄入绞股蓝皂苷提取物的实验大鼠的血清尿酸水平,尿酸生成关键酶黄嘌呤氧化酶活性,24 h尿液酸碱度、尿酸浓度及尿酸排泄量等指标进行监测。结果发现,绞股蓝皂苷可以通过抑制尿酸生成,促进排泄,抑制机体的血尿酸水平升高,有益于改善高尿酸血症患者健康状况。     

降血尿酸益生菌株的筛选和降血尿酸机理的探索

【背景】高尿酸血症是人体内血尿酸含量显著高于正常水平的代谢性疾病,利用益生菌降解食物中外源性嘌呤类成分成为治疗高尿酸血症的新方法。【目的】筛选具有降低血尿酸作用的益生菌,并探索其作用机制。【方法】利用HPLC从多株实验菌株中筛选降解核苷酸(腺苷酸、鸟苷酸)、核苷(腺苷、鸟苷)、嘌呤(黄嘌呤、次黄嘌呤、鸟嘌呤)、尿酸能力最强的益生菌。首次利用质谱定性与定量检测菌株降解核苷与核苷酸过程中代谢物的变化,结合菌株对高尿酸血症模型大鼠血尿酸水平的影响,初步探索其降低血尿酸的机理。【结果】首次筛选出具有较强降解核苷酸与核苷能力的干酪乳杆菌ZM15(CGMCC No.13980),高尿酸血症模型大鼠验证其具有降低血尿酸的作用。结果显示菌株ZM15在胞内降解核苷酸、核苷后,胞内、外均测到鸟嘌呤、黄嘌呤、次黄嘌呤,且胞内3种嘌呤含量显著高于正常菌体内含量(P0.01),尿酸和尿囊素在胞内、外均未发现。【结论】干酪乳杆菌ZM15具有较强的降解核苷酸、核苷的能力,推测其主要通过与肠道上皮细胞竞争吸收核苷酸与核苷,从而对高尿酸血症模型大鼠具有降血尿酸作用。     

血清尿酸对心血管系统及神经退行性病变的影响

尿酸是人体嘌呤代谢的最终产物。高尿酸血症,即血清尿酸水平过高,是引发痛风的主要病因。越来越多的流行病学研究将高尿酸血症与心血管系统疾病和神经退行性病变紧密联系在一起。这些研究表明,炎性反应极有可能是高尿酸水平引发痛风的致病机制。同时,炎性反应与尿酸引起的心血管系统改变息息相关。尿酸钠晶体被认为通过Toll样受体家族诱发炎症反应诱导炎症的发生。此外,可溶性尿酸可以促进自由基的生成,起到促进氧化的作用。本综述总结了近期关于高尿酸血症和心血管系统疾病的流行病学研究,简要回顾了高尿酸血症在神经退行性病变中的作用,并描述了尿酸诱导的炎症产生机制。     

鹅肌肽对高尿酸血症大鼠的干预作用研究

目的：探讨鹅肌肽对高尿酸血症大鼠的作用及其机制。方法：选用雄性SD大鼠60只,随机分为6组：空白对照组（CON）、高尿酸血症组（HUA）、别嘌呤醇组［Allo：10 mg/（kg·d）］和鹅肌肽干预组［Ans 1 mg：1 mg/（kg·d）］;［Ans 10 mg：10 mg/（kg·d）］;［Ans 100 mg：100 mg/（kg·d）］,空白对照组喂养普通大鼠饲料,其他5组均喂养高尿酸血症模型饲料,进行相应物质的灌胃,实验周期为6周,实验结束后,收集大鼠24 h尿量,评价大鼠尿酸和肾功能指标,并进行肾脏组织学观察。结果：与CON组相比,HUA组血尿酸水平显著升高（P＜0.05）,血尿素氮、尿量及尿酸排泄指标均有显著性差异（P< 0.05）。与HUA组相比,鹅肌肽干预组中,Ans 10 mg和Ans 100 mg组的血尿酸水平降低（P< 0.05）,尿量及尿酸排泄指标有显著性差异（P< 0.05）,Ans 1 mg的胱抑素C和Ans 100 mg的血清腺苷脱氨酶显著降低（P< 0.05）。组织学分析显示,鹅肌肽各干预组大鼠管腔扩张和肾小管上皮细胞空泡变性明显改善,无纤维化,与空白对照组差异较小,能明显延缓高尿酸血症大鼠的肾脏损伤。结论：鹅肌肽能降低高尿酸血症大鼠尿酸水平,可能是通过促进肾脏尿酸排泄和保护肾功能来实现的。     

慢性肾功能衰竭继发高尿酸血症促进血管钙化

本文旨在探讨高尿酸血症对肾衰血管钙化的影响及其机制。使用腺嘌呤饮食喂养的方法建立慢性肾功能衰竭的大鼠模型。将8周龄雄性Wistar大鼠随机分为对照组(正常饮食+正常饮水)、肾衰组(腺嘌呤饮食+正常饮水)和肾衰+别嘌呤醇组(腺嘌呤饮食+别嘌呤醇饮水),喂养6周后进行取材,用邻甲酚酞络合铜法和Von Kossa染色法检测大鼠腹主动脉钙含量,用real-time PCR法检测大鼠腹主动脉成骨基因(Cbfα1、Msx2、Osx和Sox9)、平滑肌细胞标志物(SM22a和Acta2)和钙化抑制因子Opn和Mgp的m RNA表达水平。结果显示,肾衰组大鼠血磷、血肌酐、血清尿素氮和血尿酸水平均显著升高,别嘌呤醇治疗可显著降低肾衰大鼠血肌酐、血清尿素氮和血尿酸水平,但是不影响血磷水平。肾衰组大鼠的腹主动脉钙含量显著高于对照组(P0.05),肾衰+别嘌呤醇组显著低于肾衰组(P0.05);肾衰组大鼠腹主动脉Cbfα1、Msx2、Osx和Sox9的m RNA水平较对照组出现显著上调,而SM22a、Acta2、Mgp和Opn的m RNA水平出现下调,在肾衰+别嘌呤醇组Msx2、Osx、SM22a和Opn的m RNA表达变化被逆转。在高磷(3 mmol/L)诱导的血管平滑肌细胞(vascular smooth muscle cells,VSMC)钙化模型中,抗氧化剂Mn TMPy P显著抑制VSMC钙化,而别嘌呤醇则无显著作用;当尿酸水平达到6和7 mg/d L时可以显著加重高磷诱导的VSMC钙化(P0.05)。以上结果提示,慢性肾功能衰竭继发的高尿酸血症可以促进VSMC向成骨/成软骨样细胞转分化,进而加剧血管钙化的发生。     

齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响

采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。     

L-阿拉伯糖对尿酸的调节作用

转录因子是一类在生物生命活动过程中起到调控作用的重要因子,参与了各种信号转导和调控过程,可以直接或间接结合在顺式作用元件上,实现调控目标基因转录效率的抑制或增强,从而使植物在应对逆境胁迫下做出反应。 WRKY转录因子在大多数植物体内都有分布,是一类进化非常保守的转录因子家族,参与植物生长发育以及响应逆境胁迫的生理过程。众多研究表明,WRKY转录因子在植物中能够应答各种生物胁迫,如细菌、病毒和真菌等;多种非生物胁迫,包括高温、冷害、高光和高盐等;以及在各种植物激素,包括茉莉酸( JA)、水杨酸( SA)、脱落酸( ABA)和赤霉素( GA)等,在其信号传递途径中都起着重要作用。 WRKY转录因子家族蛋白至少含有一段60个氨基酸左右的高度保守序列,被称为WRKY结构域,其中WRKYGQK多肽序列是最为保守的,因此而得名。该转录因子的WRKY结构域能与目标基因启动子中的顺式作用元件W￣box( TTGAC序列)特异结合,从而调节目标基因的表达,其调控基因表达主要受病原菌、虫咬、机械损伤、外界胁迫压力和信号分子的诱导。该文介绍了植物WRKY转录因子在植物应对冷害、干旱、高盐等非生物胁迫与病菌、虫害等生物胁迫反应中的重要调控功能,并总结了WRKY转录因子在调控这些逆境胁迫反应过程中的主要生理机制。     

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

BackgroundA high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified.MethodsWe used male Wistar rats, which were orally administered fructose (5 g/kg). Those rats were used in each experiment at 12 h after administration.ResultsSingle administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose.ConclusionsSingle administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia.     

Management of Hyperuricemia with Rasburicase Review

Tumor lysis syndrome (TLS) is a serious complication in patients with hematological malignancies. Massive lysis of tumor cells can lead to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic disturbances may result in renal failure, because of precipitation of uric acid crystals and calcium phosphate salts in the kidney. The standard prophylaxis or treatment of hyperuricemia consists of decreasing uric acid production with allopurinol and facilitating its excretion by urinary alkalinization and hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the conversion of hypoxanthine and xanthine into uric acid. An alternative treatment is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5–10 times more soluble than uric acid and is therefore excreted easily. In several clinical trials rasburicase, the recombinant form of urate oxidase, has shown to be very effective in preventing and treating hyperuricemia. Rasburicase, in contrast with the non‐recombinant form of urate oxidase uricozyme, is associated with a low incidence of hypersensitivity reactions. In addition to the demonstrated clinical benefit, rasburicase also proved to be a cost‐effective option in the management of hyperuricemia.     

Management of hyperuricemia with rasburicase review

Tumor lysis syndrome (TLS) is a serious complication in patients with hematological malignancies. Massive lysis of tumor cells can lead to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic disturbances may result in renal failure, because of precipitation of uric acid crystals and calcium phosphate salts in the kidney. The standard prophylaxis or treatment of hyperuricemia consists of decreasing uric acid production with allopurinol and facilitating its excretion by urinary alkalinization and hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the conversion of hypoxanthine and xanthine into uric acid. An alternative treatment is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5-10 times more soluble than uric acid and is therefore excreted easily. In several clinical trials rasburicase, the recombinant form of urate oxidase, has shown to be very effective in preventing and treating hyperuricemia. Rasburicase, in contrast with the non-recombinant form of urate oxidase uricozyme, is associated with a low incidence of hypersensitivity reactions. In addition to the demonstrated clinical benefit, rasburicase also proved to be a cost-effective option in the management of hyperuricemia.     

Relationship Between Hyperuricemia and Chronic Kidney Disease

Because approximately 70% of uric acid is excreted from the kidney, hyperuricemia occurs when renal function deteriorates. Until now, it has not been clear if the hyperuricemia seen in such renal diseases plays a role in the progression of renal disease. However, recent clinical studies show that the serum uric acid value is closely associated with hypertension in hyperuricemic patients (cross-sectional study), and also with the onset of hypertension (longitudinal study). Furthermore, one interesting report shows that treatment of hyperuricemia with allopurinol lowers blood pressure in juvenile essential hypertension patients with hyperuricemia. In addition, it is well known that hyperuricemia is closely associated with chronic kidney disease (CKD), is a risk factor for renal insufficiency in general populations, and is a poor prognostic factor of renal function in patients who also have IgA nephropathy. On the other hand, in intervention studies on hyperuricemia, the treatment of hyperuricemia with allopurinol in CKD has resulted in a fall in blood pressure and inhibition of the progression of renal damage. Conversely, the cessation of allopurinol treatment in CKD was followed by a rise in blood pressure and the development of renal damage. Furthermore, the rise of blood pressure and development of renal damage following cessation of allopurinol treatment are only seen in patients not receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). This suggests that the renin angiotensin (RA) system plays an important role in the development of hypertension and renal damage from hyperuricemia.     

Relationship between hyperuricemia and chronic kidney disease

Because approximately 70% of uric acid is excreted from the kidney, hyperuricemia occurs when renal function deteriorates. Until now, it has not been clear if the hyperuricemia seen in such renal diseases plays a role in the progression of renal disease. However, recent clinical studies show that the serum uric acid value is closely associated with hypertension in hyperuricemic patients (cross-sectional study), and also with the onset of hypertension (longitudinal study). Furthermore, one interesting report shows that treatment of hyperuricemia with allopurinol lowers blood pressure in juvenile essential hypertension patients with hyperuricemia. In addition, it is well known that hyperuricemia is closely associated with chronic kidney disease (CKD), is a risk factor for renal insufficiency in general populations, and is a poor prognostic factor of renal function in patients who also have IgA nephropathy. On the other hand, in intervention studies on hyperuricemia, the treatment of hyperuricemia with allopurinol in CKD has resulted in a fall in blood pressure and inhibition of the progression of renal damage. Conversely, the cessation of allopurinol treatment in CKD was followed by a rise in blood pressure and the development of renal damage. Furthermore, the rise of blood pressure and development of renal damage following cessation of allopurinol treatment are only seen in patients not receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). This suggests that the renin angiotensin (RA) system plays an important role in the development of hypertension and renal damage from hyperuricemia.     

尿酸性肾病中IL-1beta、IRAK-4 的表达及意义

目的：通过研究尿酸性肾病动物模型中白介素-1(IL-1)beta和白介素-1受体相关激酶4(IRAK-4) 表达的意义,了解IL-1beta信号 通路在尿酸性肾病中的作用。方法：Wistar 大鼠54 只随机分为高尿酸血症组30 只、正常组24 只,制备尿酸性肾病大鼠模型,检测 尿酸(UA)、尿素氮(BUN)、肌酐(CR)及肌酐清除率(Ccr)、24 h尿微量白蛋白(mA1b);取肾脏组织行HE 染色,观察形态学变化;免疫 组化测定IL-1beta的表达;荧光定量PCR 检测IRAK-4 mRNA的水平。结果：高尿酸组2、4、6 周时IL-1beta的表达均增加,免疫组化评 分(IHS)均明显升高(P<0.01);高尿酸血症组较正常组IRAK-4 mRNA 在2、4、6 周时均出现表达上调,4～6 周IRAK-4 mRNA表达 明显增加,与正常组比较有显著性差异(P<0.01)。结论：IL-1beta、IRAK-4 参与了尿酸性肾病炎症反应的过程,可能为尿酸性肾病治疗 提供新的可能。     

一种高尿酸血症大鼠模型诱导方法的改良和效果评价研究

目的: 探索短期内诱导高尿酸血症大鼠模型的有效方法,并对模型效果进行评价。方法: 雄性SD大鼠随机分为对照组(CT组,6只)和5个模型组(M1-M5组),每组8只;M1组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg 2次灌胃,于模型诱导的第7日1次性腹腔注射氧嗪酸钾300 mg/kg)、M2组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg灌胃2次,于模型诱导第1、3、7日每天腹腔注射1次氧嗪酸钾300 mg/kg)、M3组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg灌胃 2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、M4组(每天酵母膏20 g/kg+腺嘌呤100 mg/kg灌胃 2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、M5组(每天酵母膏30 g/kg+腺嘌呤100 mg/kg灌胃2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、CT组(5个模型组按相同的时间、体重计算等体积灌胃和腹腔注射生理盐水),造模7 d;分别在造模结束时和2周后采集24 h尿样和血样检测尿酸、肌酐水平,取肾脏和胃称重,观察肾脏病理变化。结果: 与CT组相比,造模结束后,所有模型组大鼠体重均显著降低(P＜0.01);除M2组外,其他造模组大鼠均有亡,M4组和M5组因死亡率高未做后续分析,M1和M3组分别死亡4例和2例;造模结束后,模型大鼠血尿酸、尿尿酸水平明显升高(P＜0.01),并且M2组的血尿酸水平显著高于其他各组(P＜0.05);继续喂养2周后,各模型组的血尿酸和尿尿酸水平仍显著升高(P＜0.05);各模型组大鼠肾脏重量也明显增加(P＜0.01);病理检查显示,模型组大鼠肾脏出现明显炎症反应和结构破坏。结论: 采用酵母膏(10 g/kg)、腺嘌呤(100 mg/kg)联合氧嗪酸钾(300 mg/kg)间隔(第1、3、7日)注射的方案可在短期内安全地诱导高尿酸血症大鼠模型,模型效果持续时间较长,适合在相关研究中应用。     

Effects of losartan on expression of monocyte chemoattractant protein-1 (MCP-1) in hyperuricemic nephropathy rats

Abstract

The monocyte chemoattractant protein-1 (MCP-1) plays an important role in the pathogenesis of progression of renal failure. This is based on the observations done both in various animal models of renal damage and in different types of human renal disease. During the development of non-infectious kidney stones, crystals are formed and deposited on the kidneys and the kidneys are surrounded by monocytes/macrophages. We have proposed that in response to crystal exposure, renal epithelial cells produce chemokines, which attract the monocytes/macrophages to the sites of crystal deposition. In this study, we investigated the expression of MCP-1 protein by SD rats exposed to oxonic acid (OA). Our study showed that hyperuricemia accelerates renal progression via a mechanism linked to high MCP-1 which may mediate the inflammation reaction of renal diseases induced by hyperuricemia. Losartan may retard the progression of advanced renal dysfunction, and the mechanism was partly due to blocking of renal inflammation induced by the uric acid. Because the number of experiments performed here is very few, results must be confirmed by more extensive studies with a larger sample size.     

Comprehensive analysis of mechanism underlying hypouricemic effect of glucosyl hesperidin

Hyperuricemia is caused by hepatic overproduction of uric acid and/or underexcretion of urate from the kidneys and small intestine. Although increased intake of citrus fruits, a fructose-rich food, is associated with increased risk of gout in humans, hesperidin, a flavonoid naturally present in citrus fruits, reportedly reduces serum uric acid (SUA) levels by inhibiting xanthine oxidase (XOD) activity in rats. However, the effects of hesperidin on renal and intestinal urate excretion were previously unknown. In this study, we used glucosyl hesperidin (GH), which has greater bioavailability than hesperidin, to clarify comprehensive mechanisms underlying the hypouricemic effects of hesperidin in vivo. GH dose-dependently decreased SUA levels in mice with hyperuricemia induced by potassium oxonate and a fructose-rich diet, and inhibited XOD activity in the liver. GH decreased renal urate excretion without changes in kidney URAT1, ABCG2 or GLUT9 expressions, suggesting that reducing uric acid pool size by inhibiting XOD decreased renal urate excretion. We also found that GH had no effect on intestinal urate excretion or protein expression of ABCG2. Therefore, we concluded that GH exhibits a hypouricemic effect by inhibiting XOD activity in the liver without increasing renal or intestinal urate excretion. Of note, this is the first study to elucidate the effect of a flavonoid on intestinal urate excretion using a mice model, whose findings should prove useful in future food science research in the area of urate metabolism. Taking these findings together, GH may be useful for preventing hyperuricemia, especially in people with the overproduction type.