Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Hydroxycitric Acid Inhibits Renal Calcium Oxalate Deposition by Reducing Oxidative Stress and Inflammation

Author(s): Xiao Liu, Peng Yuan, Xifeng Sun and Zhiqiang Chen*

Volume 20, Issue 7, 2020

Page: [527 - 535] Pages: 9

DOI: 10.2174/1566524020666200103141116

Price: $65

Abstract

Objective: The study aimed to evaluate the preventive effects of hydroxycitric acid（HCA） for stone formation in the glyoxylate-induced mouse model.

Materials and Methods: Male C57BL/6J mice were divided into a control group, glyoxylate(GOX) 100 mg/kg group, a GOX+HCA 100 mg/kg group, and a GOX+HCA 200 mg/kg group. Blood samples and kidney samples were collected on the eighth day of the experiment. We used Pizzolato staining and a polarized light microscope to examine crystal formation and evaluated oxidative stress via the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression of monocyte chemotactic protein-1(MCP-1), nuclear factor-kappa B (NF κ B), interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) messenger RNA (mRNA). The expression of osteopontin (OPN) and a cluster of differentiation-44(CD44) were detected by immunohistochemistry and qRT-PCR. In addition, periodic acid Schiff (PAS) staining and TUNEL assay were used to evaluate renal tubular injury and apoptosis.

Results: HCA treatment could reduce markers of renal impairment (Blood Urea Nitrogen and serum creatinine). There was significantly less calcium oxalate crystal deposition in mice treated with HCA. Calcium oxalate crystals induced the production of reactive oxygen species and reduced the activity of antioxidant defense enzymes. HCA attenuated oxidative stress induced by calcium oxalate crystallization. HCA had inhibitory effects on calcium oxalate-induced inflammatory cytokines, such as MCP-1, IL- 1 β, and IL-6. In addition, HCA alleviated tubular injury and apoptosis caused by calcium oxalate crystals.

Conclusion: HCA inhibits renal injury and calcium oxalate crystal deposition in the glyoxylate-induced mouse model through antioxidation and anti-inflammation.

Keywords: Hydroxycitric acid, kidney crystallization, oxidative stress, inflammation, calcium oxalate crystal deposition, antioxidation.

« Previous Next »
[1]
Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic diseases in America project. Prevalence of kidney stones in the United States. Eur Urol 2012; 62(1): 160-5.
[http://dx.doi.org/10.1016/j.eururo.2012.03.052] [PMID: 22498635]
[2]
Wu W, Yang B, Ou L, et al. Urinary stone analysis on 12,846 patients: a report from a single center in China. Urolithiasis 2014; 42(1): 39-43.
[http://dx.doi.org/10.1007/s00240-013-0633-0] [PMID: 24362574]
[3]
Shoag J, Halpern J, Goldfarb DS, Eisner BH. Risk of chronic and end stage kidney disease in patients with nephrolithiasis. J Urol 2014; 192(5): 1440-5.
[http://dx.doi.org/10.1016/j.juro.2014.05.117] [PMID: 24929140]
[4]
Basavaraj DR, Biyani CS, Browning AJ, Cartledge JJ. The Role of urinary kidney stone inhibitors and promoters in the pathogenesis of calcium containing renal stones. EAU-EBU Update Ser 2007; 5: 126-36.
[http://dx.doi.org/10.1016/j.eeus.2007.03.002]
[5]
Joshi S, Wang W, Peck AB, Khan SR. Activation of the NLRP3 inflammasome in association with calcium oxalate crystal induced reactive oxygen species in kidneys. J Urol 2015; 193(5): 1684-91.
[http://dx.doi.org/10.1016/j.juro.2014.11.093] [PMID: 25437532]
[6]
Ma MC, Chen YS, Huang HS. Erythrocyte oxidative stress in patients with calcium oxalate stones correlates with stone size and renal tubular damage. Urology 2014; 83(2): 510.e9-510.e17.
[http://dx.doi.org/10.1016/j.urology.2013.09.050] [PMID: 24360074]
[7]
Taguchi K, Okada A, Kitamura H, et al. Colony-stimulating factor-1 signaling suppresses renal crystal formation. J Am Soc Nephrol 2014; 25(8): 1680-97.
[http://dx.doi.org/10.1681/ASN.2013060675] [PMID: 24578130]
[8]
Tang C, Dong Z. Mitochondria in Kidney Injury: When the power plant fails. J Am Soc Nephrol 2016; 27(7): 1869-72.
[http://dx.doi.org/10.1681/ASN.2015111277] [PMID: 26744487]
[9]
Hall AM, Schuh CD. Mitochondria as therapeutic targets in acute kidney injury. Curr Opin Nephrol Hypertens 2016; 25(4): 355-62.
[http://dx.doi.org/10.1097/MNH.0000000000000228] [PMID: 27166518]
[10]
Srivastava S, Sinha D, Saha PP, Marthala H, D’Silva P. Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages. Cell Death Dis 2014.5e1394
[http://dx.doi.org/10.1038/cddis.2014.355] [PMID: 25165880]
[11]
Oh GS, Kim HJ, Choi JH, et al. Pharmacological activation of NQO1 increases NAD+ levels and attenuates cisplatin-mediated acute kidney injury in mice. Kidney Int 2014; 85(3): 547-60.
[http://dx.doi.org/10.1038/ki.2013.330] [PMID: 24025646]
[12]
Hirose M, Tozawa K, Okada A, et al. Glyoxylate induces renal tubular cell injury and microstructural changes in experimental mouse. Urol Res 2008; 36(3-4): 139-47.
[http://dx.doi.org/10.1007/s00240-008-0143-7] [PMID: 18542940]
[13]
Tsujihata M. Mechanism of calcium oxalate renal stone formation and renal tubular cell injury. Int J Urol 2008; 15(2): 115-20.
[http://dx.doi.org/10.1111/j.1442-2042.2007.01953.x] [PMID: 18269444]
[14]
Kawana H, Karaki H, Higashi M, et al. CD44 suppresses TLR-mediated inflammation. J Immunol 2008; 180(6): 4235-45.
[http://dx.doi.org/10.4049/jimmunol.180.6.4235] [PMID: 18322236]
[15]
Semwal RB, Semwal DK, Vermaak I, Viljoen A. A comprehensive scientific overview of Garcinia cambogia. Fitoterapia 2015; 102: 134-48.
[http://dx.doi.org/10.1016/j.fitote.2015.02.012] [PMID: 25732350]
[16]
Sripradha R, Magadi SG. Efficacy of garcinia cambogia on body weight, inflammation and glucose tolerance in high fat fed male wistar rats. J Clin Diagn Res 2015; 9(2): BF01-4.
[http://dx.doi.org/10.7860/JCDR/2015/12045.5577] [PMID: 25859449]
[17]
Amin KA, Kamel HH, Abd Eltawab MA. Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet. Lipids Health Dis 2011; 10: 6.
[http://dx.doi.org/10.1186/1476-511X-10-6] [PMID: 21235803]
[18]
Chung J, Granja I, Taylor MG, Mpourmpakis G, Asplin JR, Rimer JD. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition. Nature 2016; 536(7617): 446-50.
[http://dx.doi.org/10.1038/nature19062] [PMID: 27501150]
[19]
Shara M, Ohia SE, Schmidt RE, et al. Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days. Mol Cell Biochem 2004; 260(1-2): 171-86.
[http://dx.doi.org/10.1023/B:MCBI.0000026069.53960.75] [PMID: 15228099]
[20]
Ohia SE, Opere CA, LeDay AM, Bagchi M, Bagchi D, Stohs SJ. Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX). Mol Cell Biochem 2002; 238(1-2): 89-103.
[http://dx.doi.org/10.1023/A:1019911205672] [PMID: 12349913]
[21]
Pizzolato P. Histochemical recognition of calcium oxalate. J Histochem Cytochem 1964; 12: 333-6.
[http://dx.doi.org/10.1177/12.5.333] [PMID: 14193854]
[22]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[23]
Okada A, Yasui T, Hamamoto S, et al. Genome-wide analysis of genes related to kidney stone formation and elimination in the calcium oxalate nephrolithiasis model mouse: detection of stone-preventive factors and involvement of macrophage activity. J Bone Miner Res 2009; 24(5): 908-24.
[http://dx.doi.org/10.1359/jbmr.081245] [PMID: 19113933]
[24]
Khan SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol 2013; 189(3): 803-11.
[http://dx.doi.org/10.1016/j.juro.2012.05.078] [PMID: 23022011]
[25]
Khan SR. Hyperoxaluria-induced oxidative stress and antioxidants for renal protection. Urol Res 2005; 33(5): 349-57.
[http://dx.doi.org/10.1007/s00240-005-0492-4] [PMID: 16292585]
[26]
Ceban E, Banov P, Galescu A, Botnari V. Oxidative stress and antioxidant status in patients with complicated urolithiasis. J Med Life 2016; 9(3): 259-62.
[PMID: 27974930]
[27]
Patel M, Yarlagadda V, Adedoyin O, et al. Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line. Redox Biol 2018; 15: 207-15.
[http://dx.doi.org/10.1016/j.redox.2017.12.003] [PMID: 29272854]
[28]
Mulay SR, Kulkarni OP, Rupanagudi KV, et al. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J Clin Invest 2013; 123(1): 236-46.
[http://dx.doi.org/10.1172/JCI63679] [PMID: 23221343]
[29]
Habibzadegah-Tari P, Byer KG, Khan SR. Reactive oxygen species mediated calcium oxalate crystal-induced expression of MCP-1 in HK-2 cells. Urol Res 2006; 34(1): 26-36.
[http://dx.doi.org/10.1007/s00240-005-0007-3] [PMID: 16397773]
[30]
Boonla C, Hunapathed C, Bovornpadungkitti S, et al. Messenger RNA expression of monocyte chemoattractant protein-1 and interleukin-6 in stone-containing kidneys. BJU Int 2008; 101(9): 1170-7.
[http://dx.doi.org/10.1111/j.1464-410X.2008.07461.x] [PMID: 18241247]
[31]
Yasui T, Okada A, Hamamoto S, et al. Pathophysiology-based treatment of urolithiasis. Int J Urol 2017; 24(1): 32-8.
[http://dx.doi.org/10.1111/iju.13187] [PMID: 27539983]
[32]
Khaskhali MH, Byer KJ, Khan SR. The effect of calcium on calcium oxalate monohydrate crystal-induced renal epithelial injury. Urol Res 2009; 37(1): 1-6.
[http://dx.doi.org/10.1007/s00240-008-0160-6] [PMID: 19005647]
[33]
Wesson JA, Ward MD. Role of crystal surface adhesion in kidney stone disease. Curr Opin Nephrol Hypertens 2006; 15(4): 386-93.
[http://dx.doi.org/10.1097/01.mnh.0000232879.50716.6f] [PMID: 16775453]
[34]
Khan SR. Role of renal epithelial cells in the initiation of calcium oxalate stones. Nephron, Exp Nephrol 2004; 98(2): e55-60.
[http://dx.doi.org/10.1159/000080257] [PMID: 15499208]
[35]
Asselman M, Verhulst A, De Broe ME, Verkoelen CF. Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys. J Am Soc Nephrol 2003; 14(12): 3155-66.
[http://dx.doi.org/10.1097/01.ASN.0000099380.18995.F7] [PMID: 14638914]
[36]
Fujii Y, Okada A, Yasui T, et al. Effect of adiponectin on kidney crystal formation in metabolic syndrome model mice via inhibition of inflammation and apoptosis. PLoS One 2013; 8(4)e61343
[http://dx.doi.org/10.1371/journal.pone.0061343] [PMID: 23630583]

Rights & Permissions Print Cite
Article Metrics
51
World Malaria Day
© 2024 Bentham Science Publishers | Privacy Policy