Hyperuricemia is a metabolic disease caused by purine metabolic disorders that lead to the overproduction and (or) reduced excretion of uric acid, and is an important biochemical basis for gout. In the present study, a cell model of hyperuricemia was established and the anti-hyperuricemic activity of whey protein-derived peptides was studied. Thehepatic (LO2) cells were seeded into a 24-well plate and divided into two groups–normal control and model groups. After 48 h of incubation, the model group was incubated with adenosine-containing medium, while the control group was incubated with fresh basal medium. After further incubation for 36 h, xanthine oxidase was added and the incubation was continued for another 12 h. Finally, the cell culture supernatants were collected and analyzed by high performance liquid chromatography (HPLC) assays. The results demonstrated that the uric acid level of model group was significantly higher than the normal control group, and the optimal adenosine concentration for incubation, cell plating density, and optimal incubation time were 2.5 mmol/L, 105 cell/mL, and 36 h, respectively. Under the best conditions for model construction, febuxostat and whey protein hydrolysate were used to evaluate the anti-hyperuricemic activity of the model, and the results showed that the uric acid content of febuxostat group was markedly decreased in a dose-dependent manner, further suggesting that the hyperuricemia model was successfully established. After hepatic cells were incubated with whey protein hydrolysate, when whey protein-derived proteins reached a certain concentration, the level of uric acid decreased significantly compared with that of model group, indicating that whey protein hydrolysates exhibited anti-hyperuricemic activity.
[1] Puig J G, Beltran L, Chew C M, et al. Ultrasound in the diagnosis of asymptomatic hyperuricemia and gout [J]. Revista Clínica Espa?ola (English Edition), 2016, 216(8): 445-450
[2] Cesar D T, Nuria P H, Fernando P R. New medications in development for the treatment of hyperuricemia of gout [J]. Current Opinion in Rheumatology, 2015, 27(2): 164-169
[3] Choi H K, Ford E S. Prevalence of the metabolic syndrome in individuals with hyperuricemia [J]. The American Journal of Medicine, 2007, 120(5): 442-447
[4] Su P, Hong L, Zhao Y, et al. Relationship between hyperuricemia and cardiovascular disease risk factors in a Chinese population: a cross-sectional study [J]. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2015, 21: 2707-2717
[5] Chen J H, Chuang S Y, Chen H J, et al. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: A chinese cohort study [J]. Arthritis Care & Research, 2009, 61(2): 225-232
[6] See L C, Kuo C F, Chuang F H, et al. Hyperuricemia and metabolic syndrome: associations with chronic kidney disease [J]. Clinical Rheumatology, 2011, 30(3): 323-330
[7] Kuwabara M. Hyperuricemia, cardiovascular disease, and hypertension [J]. Pulse, 2016, 3(3-4): 242-252
[8] Rees F, Hui M, Doherty M. Optimizing current treatment of gout [J]. Nature Reviews Rheumatology, 2014, 10(5): 271- 283
[9] Tausche A K, Jansen T L, Schr?der H E, et al. Gout-current diagnosis and treatment [J]. Pathophysiology, 2009, 106(34): 549-555
[10] 刘佳,李玲.高尿酸血症的发病机制与药物治疗研究进展[J].国际药学研究杂志,2010,37(1):24-28
LIU Jia, LI Ling. Pathogenesy and pharmacotherapy of hyperuricemia: research advances [J]. Journal of International Pharmaceutical Research, 2010, 37(1): 24-28
[11] 刘永贵,赵丽嘉,崔艳丽,等.抗高尿酸血症药物研究进展[J].现代药物与临床,2015 30(3):345-350
LIU Yong-gui, ZHAO Li-jia, CUI Yan-li, et al. Research progress on anti-hyperuricemic drugs [J]. Drugs & Clinic, 2015, 30(3): 345-350
[12] 陈翔,蔡吓明,陈国勇.非布司他治疗痛风伴高尿酸血症疗效观察[J].中外医学研究,2015,13(34):34-36
CHEN Xiang, CAI Xia-ming, CHEN Guo-yong. Efficacy of febuxostat in gout and hyperuricemia patients [J]. Chinese and Foreign Medical Research, 2015, 13(34): 34-36
[13] Bruce S P. Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout [J]. Annals of Pharmacotherapy, 2006, 40(12): 2187-2194
[14] Baker J F, Ralph S H. Update on gout and hyperuricemia [J]. International Journal of Clinical Practice, 2010, 64(3): 371- 377
[15] Calogiuri G, Nettis E, Dileo E, et al. Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules [J]. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets- Inflammation & Allergy), 2013, 12(1): 19-28
[16] Chohan S. Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions [J]. The Journal of Rheumatology, 2011, 38(9): 1957-1959
[17] Kojima S, Kojima S, Hifumi A, et al. Therapeutic strategy for efficient reduction of serum uric acid levels with allopurinol versus benzbromarone in hyperuricemic patients with essential hypertension-A randomized crossover study (terao study) [J]. International Journal of Cardiology, 2016, 224(1): 437-439
[18] Gliozzi M, Malara N, Muscoli S, et al. The treatment of hyperuricemia [J]. International Journal of Cardiology, 2016, 213(1): 23-27
[19] Shahid H, Singh J A. Investigational drugs for hyperuricemia [J]. Expert Opinion on Investigational Drugs, 2015, 24(8): 1013-1030
[20] Moolenburgh J D, Reinders M K, Jansen T. Rasburicase treatment in severe tophaceous gout: a novel therapeutic option [J]. Clinical Rheumatology, 2006, 25(5): 749-752
[21] George J R L, Sundy J S. Pegloticase for treating refractory chronic gout [J]. Drugs of Today (Barcelona, Spain: 1998), 2012, 48(7): 441-449
[22] 金沈锐,秦旭华.痛风及高尿酸血症动物模型的研究现状和评价[J].中国实验动物学报,2005,13(1):55-58
JIN Shen-rui, QIN Xu-hua. Overview of experimental animal model of gout and hyperuricemia [J]. Acta Laboratorium Animalis Scientia Sinica, 2005, 13(1): 55-58
[23] 张雪,俸婷婷,黄俊飞,等.降尿酸药物筛选方法学研究进展[J].亚太传统医药,2015,11(6):48-49
ZHANG Xue, FENG Ting-ting, HUANG Jun-fei, et al. Uric acid drug screening methodology research progress [J]. Asia-Pacific Traditional Medicine, 2015, 11(6): 48-49
[24] Wei G N, Su Q B, Zeng X B. Screening and chemical component analysis of anti-hyperuricemic active fraction of ethanol extract from polyrhachisvicina roger in Guangxi in hyperuricemia model mice [J]. Chin. J. Pharmacol. Toxicol., 2013, 27(4): 673-7
[25] 田芳,邵春海,刘景芳.奶及奶制品摄入降低痛风患者血尿酸水平[J].上海医药,2013,34(5):9-11
TIAN Fang, SHAO Chun-hai, LIU Jing-fang. Intake of milk and dairy products reduces the serum uric acid level in gout patients [J]. Shanghai Medical & Pharmaceutical Journal, 2013, 34(5): 9-11
[26] Mandal A K, Mount D B. The molecular physiology of uric acid homeostasis [J]. Annual Review of Physiology, 2015, 77(1): 323-345
