• Logo
  • SBMUJournals

The Effects of Aqueous Extract of Eryngium Campestre on Ethylene Glycol-Induced Calcium Oxalate Kidney Stone in Rats

Hamidreza Safari, Sajjad Esmaeili, Mohammad Sadegh Naghizadeh, Mehran Falahpour, Mohammad Malekaneh, Gholamreza Anani Sarab



Purpose: This study aimed to evaluate the anti-inflammatory effect of E. campestre using the aqueous extracts, obtained from the aerial parts, on Ethylene Glycol (EG)-induced calcium oxalate kidney stone in rats.

Materials and Methods: 64 male Wistar rats were randomly divided into 8 groups. Group I was considered as negative control and received normal saline for 30 days, group II as kidney stone control received EG for 30 days, groups III to VI as prophylactic treatment received EG plus 100, 200 or 400 mg/kg extracts for 30 days and groups VI to VIII received EG as therapy from day one and 100, 200 or 400 mg/kg extract from the 15th day. On the 30thday from the start of induction, rats were euthanized. Blood was collected and the kidneys were immediately excised. Slides from each one’s kidneys were prepared and stained with Hematoxylin & Eosin method. Also levels of interleukin-1 beta (IL-1?) and interleukin-6 (IL-6) were determined in rat’s serum by competitive ELISA kit.

Results: E. campestre reduced IL-1? and IL-6 levels, showing a significant reduction for both cytokines in all prophylactic groups, especially at the dose of 400 mg/kg (P-value < .001). Moreover, IL-1? (p = .011) reduced significantly in the therapy groups in 400 mg/kg dose. Crystal count reduction was seen in all prophylactic and therapy groups in comparison with group II.

Conclusion: These results suggest that the E. campestre extract has potent suppressive effect on pro-inflammatory cytokine production in rat. Also, E. campestre decreases crystal deposition in the kidney of the hyperoxaluric rat.



Saeidi J, Bozorgi H, Zendehdel A, Mehrzad J. Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene glycol-induced kidney calculi in rats. Urology journal. 2012;9:361-6.

Pearle MS, Calhoun EA, Curhan GC, Project UDoA. Urologic diseases in America project: urolithiasis. The Journal of urology. 2005;173:848-57.

Worcester EM. Stones from bowel disease. Endocrinol Metab Clin North Am. 2002;31:979-99.

Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest. 2005;115:2598-608.

Hajzadeh MR, Khoubi A, Parizadeh SMR, Hajzadeh Z. The effect of alcoholic extract of black cumin on kidney stone caused by ethylene glycol in rats. Iranian Journal of Basic Medical Sciences. 2006;9:158-66.

Conyers R, Bais R, Rofe A. The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis. Clinical chemistry. 1990;36:1717-30.

Danpure C, Jennings P. Peroxisomal alanine: glyoxylate aminotransferase deficiency in primary hyperoxaluria type I. FEBS letters. 1986;201:20-34.

Hoppe B, Beck BB, Milliner DS. The primary hyperoxalurias. Kidney international. 2009;75:1264-71.

Robijn S, Hoppe B, Vervaet BA, D'haese PC, Verhulst A. Hyperoxaluria: a gut–kidney axis? Kidney international. 2011;80:1146-58.

Govindaraj A, Selvam R. Increased calcium oxalate crystal nucleation and aggregation by peroxidized protein of human kidney stone matrix and renal cells. Urological research. 2001;29:194-8.

Terlecki RP, Triest JA. A contemporary evaluation of the auditory hazard of extracorporeal shock wave lithotripsy. Urology. 2007;70:898-9.

Bardaoui M, Sakly R, Neffati F, Najjar MF, El Hani A. Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in rats. Experimental and Toxicologic Pathology. 2010;62:573-6.

Hirayama H, Wang Z, Nishi K, et al. Effect of Desmodium styracifolium‐triterpenoidon Calcium Oxalate Renal Stones. BJU International. 1993;71:143-7.

Selvam R, Kalaiselvi P, Govindaraj A, Murugan VB, Kumar AS. Effect of A. lanata leaf extract and Vediuppu chunnam on the urinary risk factors of calcium oxalate urolithiasis during experimental hyperoxaluria. Pharmacological Research. 2001;43:89-93.

Cao Z, Liu J, Zhou S, Wu W, Yin C, Wu J. The effects of the active constituents of Alisma orientalis on renal stone formation and bikunin expression in rat urolithiasis model. Zhonghua yi xue za zhi. 2004;84:1276-9.

Erdelmeier CA, Sticher O. A cyclohexenone and a cyclohexadienone glycoside from Eryngium campestre. Phytochemistry. 1986;25:741-3.

Ingram M. Species account: Eryngium campestre. Botanical Societ of the British Isles. 2006.

Lev E. Reconstructed materia medica of the Medieval and Ottoman al-Sham. Journal of Ethnopharmacology. 2002;80:167-79.

Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 2nd ed: Medical Economics Company, New Jersey; 2000.

Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237.

Mulay SR, Kulkarni OP, Rupanagudi KV, et al. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest. 2013;123:236-46.

Anders H-J, Muruve DA. The inflammasomes in kidney disease. Journal of the American Society of Nephrology. 2011;22:1007-18.

Mulay SR, Evan A, Anders H-J. Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease. Nephrology Dialysis Transplantation. 2013;29:507-14.

Suen J-L, Liu C-C, Lin Y-S, Tsai Y-F, Juo S-HH, Chou Y-H. Urinary chemokines/cytokines are elevated in patients with urolithiasis. Urological research. 2010;38:81-7.

Ghazali A, Fuentes V, Desaint C, et al. Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria. The Journal of Clinical Endocrinology & Metabolism. 1997;82:32-8.

Green ML, Hatch M, Freel RW. Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats. American Journal of Physiology-Renal Physiology. 2005;289:F536-F43.

Zuckerman JM, Assimos DG. Hypocitraturia: pathophysiology and medical management. Reviews in urology. 2009;11:134.

Fan J, Glass MA, Chandhoke PS. Impact of ammonium chloride administration on a rat ethylene glycol urolithiasis model. Scanning Microsc. 1999;13:299-306.

Khan SR. Animal model of calcium oxalate nephrolithiasis. Calcium oxalate in biological systems: CRC Press, Boca Raton; 1995:343-59.

Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clinical Journal of the American Society of Nephrology. 2011;6:2069-75.

Okada A, Yasui T, Fujii Y, et al. Renal macrophage migration and crystal phagocytosis via inflammatory‐related gene expression during kidney stone formation and elimination in mice: Detection by association analysis of stone‐related gene expression and microstructural observation. Journal of Bone and Mineral Research. 2010;25:2701-11.

Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease. Nature. 2010;464:1357.

Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320:674-7.

Leussink BT, Nagelkerke JF, van de Water B, et al. Pathways of proximal tubular cell death in bismuth nephrotoxicity. Toxicology and applied pharmacology. 2002;180:100-9.

Küpeli E, Kartal M, Aslan S, Yesilada E. Comparative evaluation of the anti-inflammatory and antinociceptive activity of Turkish Eryngium species. Journal of ethnopharmacology. 2006;107:32-7.

Hiller K, Keipert M, Pfeifer S, Kraft R. The leaf sapogenin spectrum in Eryngium planum L. 20. Contribution on the content of several Saniculoideae. Die Pharmazie. 1974;29:54-7.

Hiller K, Von Mach B, Franke P. Saponins of Eryngium maritimum L. 25. Contents of various Saniculoideae. Die Pharmazie. 1975;31:53-.

Jacker H, Hiller K. The antiexudative effect of saponin-5 from Eryngium planum L. and Sanicular europaea L. Die Pharmazie. 1975;31:747-8.

Strzelecka M, Bzowska M, Koziel J, et al. Anti-inflammatory effects of extracts from some traditional Mediterranean diet plants. Journal of Physiology and Pharmacology. Supplement. 2005;56:139-56.

Stalinska K, Guzdek A, Rokicki M, Koj A. Transcription factors as targets of the anti-inflammatory treatment. A cell culture study with extracts from some Mediterranean diet plants. Journal of Physiology and Pharmacology. Supplement. 2005;56:157-69.

Garcia M, Saenz M, Gomez M, Fernandez M. Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models. Phytotherapy Research. 1999;13:78-80.

Kartal M, Mitaine-Offer A-C, Abu-Asaker M, et al. Two new triterpene saponins from Eryngium campestre. Chemical and pharmaceutical bulletin. 2005;53:1318-20.

Kartal M, Mitaine-Offer A-C, Paululat T, et al. Triterpene saponins from Eryngium campestre. Journal of natural products. 2006;69:1105-8.

Conea S, Parvu A, Taulescu M, Vlase L. Effects of Eryngium planum and Eryngium campestre extracts on ligatureinduced rat periodontitis. Digest Journal of Nanomaterials and Biostructures. 2015;10:693-704.

KiMuRA Y, YAsuKAwA K, TAKIDO M, AKIHISA T, TAMURA T. Inhibitory effect of some oxygenated stigmastane-type sterols on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Biological and Pharmaceutical Bulletin. 1995;18:1617-9.

Naghii MR, Mofid M, Hedayati M, Khalagi K. Antioxidants inhibition of high plasma androgenic markers in the pathogenesis of ethylene glycol (EG)-induced nephrolithiasis in Wistar rats. Urolithiasis. 2014;42:97-103.

Nebija F, Stefkov G, Karapandzova M, Stafilov T, Panovska TK, Kulevanova S. Chemical characterization and antioxidant activity of Eryngium campestre L., Apiaceae from Kosovo. Macedonian Pharmacology Bulletin. 2009;55:22-32.

Corresponding Author:

Gholamreza Anani Sarab

Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

Mobile: +989151605847

Fax: +985631631600

E-mail address: ghansa@yahoo.com

Table1: Effect of E. campestre on calcium oxalate crystal deposits in urolithiasis induced rat.

Control groups Prophylactic groups treatment groups

Parameter NC KSC P100 P200 P400 T100 T200 T400

Calcium oxalate crystals

7 ±0.6*

5 ±9.1


8 ±2.6*




9 ±4.2*

* The mean differences in comparison with KSC group is significant at the <0.05 level.

DOI: http://dx.doi.org/10.22037/uj.v0i0.4287


  • There are currently no refbacks.