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Molecular mechanisms involved in the protective effect of the chloroform extract of Selaginella lepidophylla (Hook. et Grev.) Spring in a lithiasic rat model

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Abstract

Urolithiasis is a multifaceted process, progressing from urine supersaturation to the formation of mature renal calculi. Calcium oxalate, the main component of kidney stones, has toxicological effects on renal epithelial cells. Some medicinal plants have shown pharmacological effects against renal lithiasis, such as Selaginella lepidophylla (Hook. et Grev) Spring, a plant empirically used in Mexico for its diuretic and antilithiasic activity. The plant was identified and ground, and a chloroform extract (CE) was obtained. Urolithiasis was induced in Wistar female rats by administration of ethylene glycol and ammonium chloride for 21 days. Urolithiasis rats were treated with the CE (50 mg/kg) for 21 days. Osmolality, creatinine, sodium and potassium concentrations were measured in blood and urine. Glomerular filtration rate (GFR), and electrolytic and water balances were calculated. Urinary oxalic acid concentration was measured. Apoptosis, lipoperoxidation, ROS and p-amino hippuric acid were determined in cortical tissue. Urolithiasis rats showed a decrease of urinary flow, GFR, electrolytic balance, renal tubular secretion and ATP concentration and increase of urinary oxalic acid, lipoperoxidation, oxidative stress and apoptosis in cortical tissue. After treatment with the CE, urinary flow rate, GFR and renal tubular secretion levels were recovered; on the other hand, serum creatinine and urinary oxalic acid decreased on day 21. CE of Selaginella lepidophylla prevented the damage caused by lithiasic process by improving the active secretion in the proximal tubules, counteracting the ROS and lipoperoxidation effects by oxalate and decreased the OAT3 expression on kidney.

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References

  1. Wasserstein AG (2011) Epidemiology and natural history of nephrolithiasis. Clin Rev Bone Miner Metab 9:165–180

    Article  Google Scholar 

  2. Sterret SP, Nakada SY (2011) Chapter 56: medical management of idiopathic calcium stone disease. In: Rao PN, Preminger GM, Kavanagh JP (eds) Urinary tract stone disease. Springer, London, pp 667–672

    Google Scholar 

  3. Press SM, Smith AD (1995) Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain. Urology 45(5):753–757. doi:10.1016/S0090-4295(99)80078-8

    Article  PubMed  CAS  Google Scholar 

  4. Rabinovich YI, Esayanur M, Daosukho S, Byer KJ, El-Shall HE, Khan SR (2006) Adhesion force between calcium oxalate monohydrate crystal and kidney epithelial cells and possible relevance for kidney stone formation. J Colloid Interface Sci 300(1):131–140. doi:10.1016/j.jcis.2006.03.070

    Article  PubMed  CAS  Google Scholar 

  5. Chauvet MC, Ryall RL (2005) Intracrystalline proteins and calcium oxalate crystal degradation in MDCK II cells. J Struct Biol 151(1):12–17. doi:10.1016/j.jsb.2005.04.005

    Article  PubMed  CAS  Google Scholar 

  6. Lieske JC, Norris R, Swift H, Toback FG (1997) Adhesion, internalization and metabolism of calcium oxalate monohydrate crystals by renal epithelial cells. Kidney Int 52(5):1291–1301

    Article  PubMed  CAS  Google Scholar 

  7. Bigelow MW, Wiessner JH, Kleinman JG, Mandel NS (1996) Calcium oxalate-crystal membrane interactions: dependence on membrane lipid composition. J Urol 155(3):1094–1098

    Article  PubMed  CAS  Google Scholar 

  8. Moe OW (2006) Kidney stones: pathophysiology and medical management. Lancet 367(9507):333–344. doi:10.1016/S0140-6736(06)68071-9

    Article  PubMed  CAS  Google Scholar 

  9. Yamaguchi S, Wiessner JH, Hasegawa AT, Hung LY, Mandel GS, Mandel NS (2005) Study of a rat model for calcium oxalate crystal formation without severe damage in selected conditions. Int J Urol 12:290–298

    Article  PubMed  CAS  Google Scholar 

  10. Knight TF, Sansom SC, Senekjian HO, Weinman EJ (1981) Oxalate secretion in the rat proximal tubule. Am J Physiol 240(4):295–298

    Google Scholar 

  11. Wang T, Thurgood LA, Grover PK, Ryall RL (2010) A comparison of the binding of urinary calcium oxalate monohydrate and dihydrate crystals to human kidney cells in urine. BJU Int 106(11):1768–1774

    Article  PubMed  CAS  Google Scholar 

  12. Farooq SM, Asokan D, Sakthivel R, Kalaiselvi P, Varalakshmi P (2004) Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury. Clin Chim Acta 348(1–2):199–205. doi:10.1016/j.cccn.2004.05.016

    Article  PubMed  CAS  Google Scholar 

  13. Guo C, McMartin KE (2005) The cytotoxicity of oxalate, metabolite of ethylene glycol, is due to calcium oxalate monohydrate formation. Toxicology 208(3):347–355. doi:10.1016/j.tox.2004.11.029

    Article  PubMed  CAS  Google Scholar 

  14. Jeong BC, Kwak C, Cho KS, Kim BS, Hong SK, Kim JI, Lee C, Kim HH (2005) Apoptosis induced by oxalate in human renal tubular epithelial HK-2 cells. Urol Res 33(2):87–92. doi:10.1007/s00240-004-0451-5

    Article  PubMed  CAS  Google Scholar 

  15. Khan SR (1995) Calcium oxalate crystal interaction with renal tubular epitelium, mechanism of crystal adhesion and its impact on stone development. Urol Res 23:71–79

    Article  PubMed  CAS  Google Scholar 

  16. Vaidyanathan S, Johnson H, Singh G, Hughes P, Soni BM, Parsons KF, Sett P (2002) Atrophy of kidney following extracorporeal shock wave lithotripsy of renal calculus in a paraplegic patient with marked spinal curvature. Spinal Cord 40(11):609–614. doi:10.1038/sj.sc.3101350

    Article  PubMed  CAS  Google Scholar 

  17. Kim TB, Park HK, Lee KY, Kim KH, Jung H, Yoon SJ (2010) Life-threatening complication after extracorporeal shock wave lithotripsy for a renal stone: a hepatic subcapsular hematoma. Korean J Urol 51(3):212–215. doi:10.4111/kju.2010.51.3.212

    Article  PubMed  CAS  Google Scholar 

  18. Smith CL, Guay DRP (1992) Nephrolithiasis. In: Di Piro JT, Talbert RL, Hyes PE, Yee GC, Matzke GR, Posey LM (eds) Pharmacotherapy and pathophysiologic approach. Elsevier, New York, pp 720–736

    Google Scholar 

  19. Grases F, Melero G, Costa-Bauza A, Prieto R, March JG (1994) Urolithiasis and phytotherapy. Int Urol Nephrol 26(5):507–551

    Article  PubMed  CAS  Google Scholar 

  20. Grases F, Costa-Bauza A (2000) Phytotherapy of renal lithiasis: myth and reality. Med Clin 115(20):779–782

    Article  CAS  Google Scholar 

  21. Hadjzadeh MA, Khoei A, Hadjzadeh Z, Parizady M (2007) Ethanolic extract of Nigella sativa L seeds on ethylene glycol-induced kidney calculi in rats. Urol J 4(2):86–90

    PubMed  Google Scholar 

  22. Campos AH, Schor N (1999) Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis. Nephron 81:393–397

    Article  PubMed  CAS  Google Scholar 

  23. Nizami AN, Rahman MA, Ahmed NU, Islam MS (2012) Whole Leea macrophylla ethanolic extract normalizes kidney deposits and recovers renal impairments in a ethylene glycol-induced urolithiasis model of rats. Asian Pac J Trop Med 5(7):533–538

    Article  PubMed  Google Scholar 

  24. Khan A, Khan SR, Gilani AH (2012) Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica. Urol Res 40:671–681

    Article  PubMed  CAS  Google Scholar 

  25. Karadi RV, Gadge NB, Alagawadi KR, Savadi RV (2006) Effect of Moringa oleifera Lam. root-wood on ethylene glycol induced urolithiasis in rats. J Ethnopharmacol 105:306–311

    Article  PubMed  Google Scholar 

  26. Martínez M (1989) Las plantas medicinales de México. Ediciones Botas, Mexico, pp 124–125

    Google Scholar 

  27. Estevez-Carmona MM (2009) Evaluación terapéutica de los extractos de Selaginella lepidophylla (Hook. et Grev.) Spring en la urolitiasis en rata. Dissertation, Instituto Politécnico Nacional

  28. Cheng P, Ma YB, Yao SY, Zhang Q, Wang EJ, Yan MH, Zhang XM, Zhang FX, Chen JJ (2007) Two new alkaloids and active anti-hepatitis B virus constituents from Hypserpa nitida. Bioorg Med Chem Lett 17(19):5316–5320. doi:10.1016/j.bmcl.2007.08.027

    Article  PubMed  CAS  Google Scholar 

  29. Aiyelaagbe OO, Osamudiamen PM (2009) Phytochemical screening for active compounds in Magnifera indica leaves from Ibadan, Oyo State. Plant Sci Res 2(1):11–13

    Google Scholar 

  30. McMartin KE, Wallace KB (2005) Calcium oxalate monohydrate, a metabolite of ethylene glycol, is toxic for rat renal mitochondrial function. Toxicol Sci 84:195–200

    Article  PubMed  CAS  Google Scholar 

  31. Estevez-Carmona MM, Meléndez-Camargo E, Ortiz-Butron R, Pineda-Reynoso M, Franco-Colin M, Cano-Europa E (2012) Hypothyroidism maintained reactive oxygen species–steady state in the kidney of rats intoxicated with ethylene glycol: effect related to an increase in the glutathione redox environment. Toxicol Ind Health. doi:10.1177/07482:1-12

    PubMed  Google Scholar 

  32. Meléndez E, Berdeja B, Miranda G (2004) Diuretic effect of the aqueous extract of Bidens odorata in the rat. J Ethnopharmacol 95:363–366

    Article  Google Scholar 

  33. Reyes JL, Melendez E, Alegría A, Jaramillo-Juárez F (1998) Influence of sex differences on the renal secretion of organic anions. Endocrinology 139(4):1581–1587

    Article  PubMed  CAS  Google Scholar 

  34. Hodgkinson A (1970) Determination of oxalic acid in biological material. Clin Chem 16(7):547–557

    CAS  Google Scholar 

  35. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  36. Melendez ME, Lozano M (1998) Renal and hepatic interactions of acetaminophen and amikacin in the infant rat. Proc West Pharmacol Soc 41:61–63

    Google Scholar 

  37. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CCG, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95:15735–15740

    Article  PubMed  CAS  Google Scholar 

  38. Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27(5–6):612–616

    Article  PubMed  CAS  Google Scholar 

  39. Di Giusto G, Anzai N, Ruiz ML, Endou H, Torres AM (2009) Expression and function of OAT1 and OAT3 in rat kidney exposed to mercuric chloride. Arch Toxicol 83(10):887–897. doi:10.1007/s00204-009-0445-8

    Article  PubMed  Google Scholar 

  40. Atmani F (2003) Medical management of urolithiasis, what opportunity for phytotherapy? Front Biosci 8:507–514

    Article  Google Scholar 

  41. Vázquez MA, Meléndez ME, Arreguín L (2005) Estudio etnobotánico de Selaginella lepidophylla (Hook. et Grev.) Spring (Selanellaceae-pteridophyta) en San José Xicohténcatl municipio de Huamantla, Tlaxcala, México. Polibotánica 19:105–115

    Google Scholar 

  42. Escobar PF, Howard JL, Kelly J, Roland PY, Grendys EC, Dosoretz DE, Orr JW Jr (2008) Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities. Int J Gynecol Cancer 18(4):862–867. doi:10.1111/j.1525-1438.2007.01079.x

    Article  PubMed  CAS  Google Scholar 

  43. Mardani P, Moshtaghian J, Mahzooni P, Moradi M (2011) The effects of ethylene glycol on factors influencing urolithiasis in rat. Int J Nat Eng Sci 5(2):01–06

    CAS  Google Scholar 

  44. Fan J, Glass MA, Chandhoke PS (1999) Impact of ammonium chloride administration on a rat ethylene glycol urolithiasis model. Scanning Microsc 13(2–3):299–306

    Google Scholar 

  45. Knoll T, Steidler A, Trojan L, Sagi S, Schaaf A, Yard B, Michel MS, Alken P (2004) The influence of oxalate on renal epithelial and interstitial cells. Urol Res 32(4):304–309. doi:10.1007/s00240-004-0429-3

    Article  PubMed  CAS  Google Scholar 

  46. Gonzalez-Buitrago JM, Ferreira L, Lorenzo I (2007) Urinary proteomics. Clin Chim Acta 375(1–2):49–56. doi:10.1016/j.cca.2006.07.027

    Article  PubMed  CAS  Google Scholar 

  47. Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, Tan DX, Reiter RJ (2008) Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Digest Dis Sci 53(10):2592–2603. doi:10.1007/s10620-007-0195-5

    Article  PubMed  CAS  Google Scholar 

  48. Khan A, Bashir S, Khan SR, Gilani A (2011) Antiurolithic activity of Origanum vulgare is mediated through multiple pathways. BMC Complement Altern Med 11:96. doi:10.1186/1472-6882-11-96

    Article  PubMed  Google Scholar 

  49. Lee HJ, Jeong SJ, Park MN, Linnes M, Han HJ, Kim JH, Lieske JC, Kim S (2012) Gallotannin suppresses calcium oxalate crystal binding and oxalate-induced oxidative stress in renal epithelial cells. Biol Pharm Bull 35(4):539–544

    Article  PubMed  CAS  Google Scholar 

  50. Joshi S, Saylor BT, Wang W, Peck AB, Khan SR (2012) Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. PLoS ONE 7(10):e47738. doi:10.1371/journal.pone.0047738

    Article  PubMed  CAS  Google Scholar 

  51. Miyazawa K, Aso H, Kanaya T, Kido T, Minashima T, Watanabe K, Ohwada S, Kitazawa H, Rose MT, Tahara K, Yamasaki T, Yamaguchi T (2006) Apoptotic process of porcine intestinal M cells. Cell Tissue Res 323(3):425–432. doi:10.1007/s00441-005-0086-z

    Article  PubMed  Google Scholar 

  52. Itoh Y, Yasui T, Okada A, Tozawa K, Hayashi Y, Kohri K (2005) Examination of the anti-oxidative effect in renal tubular cells and apoptosis by oxidative stress. Urol Res 33:261–266

    Article  PubMed  Google Scholar 

  53. Vanachayangkul P, Byer K, Khan S, Butterweck V (2010) An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. Phytomedicine 17:653–658

    Article  PubMed  CAS  Google Scholar 

  54. Preitner F, Bonny O, Laverriere A, Rotman S, Firsov D, Da Costa A, Metref S, Thorens B (2009) Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proc Natl Acad Sci USA 106(36):15501–15506. doi:10.1073/pnas.0904411106

    Article  PubMed  CAS  Google Scholar 

  55. Verkoelen CF, Romijn JC (1996) Oxalate transport and calcium oxalate renal stone disease. Urol Res 24:183–191

    Article  PubMed  CAS  Google Scholar 

  56. Habu Y, Yano I, Okuda M, Fukatsu A, Inui K (2005) Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after hyperuricemia in the rat kidney. Biochem Pharm 69(6):993–999. doi:10.1016/j.bcp.2004.12.004

    Article  PubMed  CAS  Google Scholar 

  57. Smeets B, Te Loeke NA, Dijkman HB, Steenbergen ML, Lensen JF, Begieneman MP, Van Kuppevelt TH, Wetzels JF, Steenbergen EJ (2004) The parietal epithelial cell: a key player in the pathogenesis of focal segmental glomerulosclerosis in Thy-1.1 transgenic mice. J Am Soc Nephrol 15(4):928–939

    Article  PubMed  Google Scholar 

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Acknowledgments

This research was partially supported by the Secretaría de Investigación y Posgrado (IPN) and the Consejo Nacional de Ciencia y Tecnología (Conacyt) under grant number 152416. M.M.E.C is a PhD fellow from Conacyt (Grant number 211857).

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  1. Laboratorio de Farmacología y Toxicología Renal y Hepática, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu, Esq. Manuel Luis Stampa S/N, U.P. Adolfo López Mateos, 07738, México, D.F., México

    Estévez-Carmona María Mirian & Meléndez-Camargo María Estela

  2. Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508 Col. San Pedro Zacatenco, 07360, México, D.F., México

    Narvaéz-Morales Juanita & Barbier Olivier Christophe

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  1. Estévez-Carmona María Mirian
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  3. Barbier Olivier Christophe
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Correspondence to Meléndez-Camargo María Estela.

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Mirian, EC.M., Juanita, NM., Christophe, B.O. et al. Molecular mechanisms involved in the protective effect of the chloroform extract of Selaginella lepidophylla (Hook. et Grev.) Spring in a lithiasic rat model. Urolithiasis 41, 205–215 (2013). https://doi.org/10.1007/s00240-013-0556-9

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