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A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats

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Abstract

We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n = 8) was the normal control; group 2 (n = 11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p = 0.059) and significantly lower serum phosphorus (p = 0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p = 0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.

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References

  1. http://210.69.214.131:/webdata/AttachFiles/Attach_8327_2_94_css.pdf

  2. http://210.69.214.131:/webdata/AttachFiles/Attach_2493_1_2-2-4.pdf

  3. Ho SZ, Kuo HC (2002) Pathogenesis and epidemiology of urolithiasis. Tzu Chin Med J 14:337–346

    Google Scholar 

  4. Menon M, Resnick MI (2002) Urinary lithiasis: etiology, diagnosis, and medical management. In: Walsh PC, Retik AB, Vaughan ED Jr., Wein AJ (eds) Campbell’s urology. 8th ed. WB Saunders, Philadelphia

    Google Scholar 

  5. Lee YH, Huang WC, Tsai JY (2002) Epidemiological studies on the prevalence of upper urinary calculi in Taiwan. Urol Int 68:172–177

    Article  PubMed  Google Scholar 

  6. Kim HH, Jo MK, Kwak C, Park SK, Yoo KY, Kang D, Lee C (2002) Prevalence and epidemiologic characteristics of urolithiasis in Seoul, Korea. Urology 59:517–521

    Article  PubMed  Google Scholar 

  7. Yoshida O, Terai A, Ohkawa T, Okada Y (1999) National trend of the incidence of urolithiasis in Japan from 1965 to 1995. Kidney Int 56:1899–1904

    Article  PubMed  CAS  Google Scholar 

  8. http://en.wikipedia.org/wiki/Taiwan#Environment_and_pollution

  9. http://en.wikipedia.org/wiki/List_of_countries_by_population_density#_note-cia

  10. Cao ZG, Liu JH, Zhou SW (2004) Effect of alisma orientalis extract on renal stone formation and the expression of inter-alpha-trypsin inhibitor in rat urolithiasis model. Chin J Exp Surg 21:295–297

    Google Scholar 

  11. Liu QL, Sato S, Kishikawa T (2001) Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats. Med Electron Microsc 34: 103–114

    Article  PubMed  CAS  Google Scholar 

  12. Hattori T, Hayashi K, Nagao T (1992) Studies on antinephritic effects of plant components(3): effect of pachyman, a main component of Poria cocos Wolf on original-type anti-GBM nephritis in rats and its mechanisms. Jpn J Pharmacol 59:89–96

    Article  PubMed  CAS  Google Scholar 

  13. Bensky D, Barolet R (eds) (1990) Chinese herbal medicine: Formulas & Strategies. Eastland, Seatle, Washington

  14. Chen YC, Ho CY, Chen LD, Hsu SF, Chen WC (2007) Wu-Ling-San formula inhibits the crystallization of calcium oxalate in vitro. Am J Chin Med 35:533–541

    Article  PubMed  CAS  Google Scholar 

  15. Nelde HJ, Bichler KH, Strohmaier WL (1988) Nephrocalcinosis in the kidney of the rat on atherogenic diet and the efffect of calcium antagonists (nifedipine). In: Bichler KN, Strohmaier WL (eds) Nephrocalcinosis calcium antagonists and kidney, Springer-Verlag, Berlin pp 113–125

    Google Scholar 

  16. Lee YH, Chang LS, Chen MT (1991) Characterization of ethylene glycol induced urolithiasis modle in rats. J Urol ROC 2:518–524

    Google Scholar 

  17. Lee YH, Huang WC, Chiang H (1992) Determinant role of testosterone in the pathogenesis of urolithiasis in rats. J Urol 147:1134–1138

    PubMed  CAS  Google Scholar 

  18. Lee YH, Tsai JY, Huang JK (2000) Combined use of 30% lactose rich diet and 1% ethylene glycol: a new animal model for study of urolithiasis. J Urol ROC 11:149–154

    Google Scholar 

  19. Leth PM, Gregersen M (2005) Ethylene glycol poisoing. Forensic Sci Int 155:179–184

    Article  PubMed  CAS  Google Scholar 

  20. Green ML, Hatch M, Freel RW (2005) Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats. Am J Physiol Renal Physiol 289:F536–F543

    Article  PubMed  CAS  Google Scholar 

  21. Selvam R, Kalaiselvi P, Govindaraj A (2001) Effect of A. Lanata leaf extract and Vediuppu chunnam on the urinary risk factors of calcium oxalate urolithiasis during experimental hyperoxaluria. Pharmacol Res 43:89–92

    Article  PubMed  CAS  Google Scholar 

  22. Das I, Gupta SK, Ansari SA (2005) In vitro inhibition and dissolution of calcium oxalate by edible plant Trianthema monogyna and pulse Macrotyloma uniflorum extracts. J Cryst Growth 273:546–554

    Article  CAS  Google Scholar 

  23. Viel TA, Domingos CD, Monteriro APS (1999) Evaluation of the antiurolithiatic activity of the extract of Costus spiralis Roscoe in rats. J Ethnopharmacol 66:193–198

    Article  Google Scholar 

  24. Gohel MDI, Wong SP (2006) Chinese herbal medicines and their efficacy in treating renal stones. Urol Res 34:365–372

    Article  PubMed  Google Scholar 

  25. Cao ZG, Liu JH, Zhou SW (2004) The effect of the active constituents of Alisma orientalis on renal stone formation and bikunin expression in rat urolithiasis model. Matl Med J China 84:1276–1279

    CAS  Google Scholar 

  26. Suzuki K, Kawamura K, Tsugawa R (1999) Formation and growth inhibition of calcium oxalate crystals by Takusha (Alismatis rhizoma). Scanning Microsc 13:183–189

    Google Scholar 

  27. Yin CP, Liu JH, Zhang YS (1997) Effects of Alisma orientalis Juzep on calcium oxalate crystallization in vitro and calcium oxalate renal stone in rats. Acta Univ Med Tongji 26:99–101

    Google Scholar 

  28. Wang SY, Deng CQ, Shi ZL (2003) Influcence of Rhizoma alismatis on inhibition of renal stone formation. J Guangzhou Univ Tradit Chin Med 20:294–296

    Google Scholar 

  29. Yasui T, Fujita K, Sato M (1999) The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model. Urol Res 27:194–199

    Article  PubMed  CAS  Google Scholar 

  30. Yashimura K, Miake O, Okuyama A (1998) Effect of chorei-to and gorei-san on calcium oxalate crystallization in human urine. Hinyokika Kiyo 44:13–16

    Google Scholar 

  31. Wesson JA, Johnson RJ, Mazzali M (2003) Osteopontin is a critical inhibitor of Calcium oxalate crystal formation and retension in renal tubules. J Am Soc Nephrol 14:139–147

    Article  PubMed  CAS  Google Scholar 

  32. Grover PK, Dogra SC, Davidson BP (2000) The prothrombin gene is expressed in the rat kidney: implications for urolithiasis research. Eur J Biochem 267:61–67

    Article  PubMed  CAS  Google Scholar 

  33. Kumar V, Lieske JC (2006) Protein regulation of intrarenal crystallization. Curr Opin Nephrol Hypertens 15:374–380

    Article  PubMed  CAS  Google Scholar 

  34. Umekawa T, Chegini N, Khan SR (2003) Increase expression of monocyte chemoattractant protein-1(MCP-1) by renal epithelial cells in culture on exposure to calcium oxalate, phosphate and uric acid crystals. Nephrol Dial Transplant 18:664–669

    Article  PubMed  CAS  Google Scholar 

  35. Umekawa T, Hatanaka Y, Kurita T (2004) Effect of angiotensinII receptor blocakge on osteoponton expression and calcium oxalate crystal deposition in rat kidneys. J Am Soc Nephrol 15:653–644

    Article  CAS  Google Scholar 

  36. Coe FC, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115:2598–2608

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the National Science Counsel of Taiwan (NSC 96-2314-B-039-005).

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Authors and Affiliations

  1. Graduate Institute of Chinese Medical Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan

    Chou-Huang Tsai, Yu-Cheng Chen, Tien-Chien Pan & Chien-Yi Ho

  2. Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

    Yu-Cheng Chen

  3. School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

    Lieh-Der Chen

  4. Department of Integrated Chinese and Western Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    Tien-Chien Pan

  5. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan

    Chien-Yi Ho

  6. Department of Pathology, College of Medicine, China Medical University, Taichung, Taiwan

    Ming-Tsung Lai

  7. College of Chinese Medicine, China Medical University, Taichung, Taiwan

    Fuu-Jen Tsai

  8. Asia University, Taichung, Taiwan

    Fuu-Jen Tsai

  9. Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

    Wen-Chi Chen

  10. Department of Urology, China Medical University Hospital, No.91 Hsueh-Shih Road, Taichung, Taiwan

    Wen-Chi Chen

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  1. Chou-Huang Tsai
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Correspondence to Wen-Chi Chen.

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Tsai, CH., Chen, YC., Chen, LD. et al. A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats. Urol Res 36, 17–24 (2008). https://doi.org/10.1007/s00240-007-0122-4

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