Prophylaxis of Experimentally Induced Calcium Oxalate Nephrolithiasis in Rats by Zhulingtang, a Traditional Chinese Herbal Formula

Background: Zhulingtang (ZLT), a traditional Chinese medicine formula, was used to evaluate the antilithic effects of experimentally induced calcium oxalate (CaOx) nephrolithiasis in ethylene glycol (EG)-fed rats. Materials and Methods: A total of 35 male Sprague-Dawley rats were randomly divided into 4 groups. Rats in group 1 (n = 8) served as the normal control. Rats in group 2 (n = 11) were treated with gastric gavages of starch as placebo and 0.75% EG as a stone inducer. Rats in group 3 (n = 8) were given 0.75% EG and a low dose (305 mg/kg) of ZLT. Rats in group 4 (n = 8) were treated with EG and a high dose (915 mg/kg) of ZLT. Twenty-four-hour urine and blood samples were collected at the beginning and at the end of the experiment for biochemical analysis. The histological appearances of the kidneys were observed under a polarized light microscope, and the crystal deposits were evaluated by a semiquantitative scoring method, computer assisted with ImageScoring software. Results: Our results revealed that rats fed with 0.75% EG for 4 weeks successfully produced renal deposition of CaOx. The severities of crystal deposition were significantly reduced in the 2 ZLT-fed groups compared with the placebo group (p = 0.025 and 0.047, respectively). Rats in the low-dose ZLT and placebo groups exhibited significantly lower serum phosphorus in comparison with the control rats (p = 0.005 and 0.03, respectively). Rats of the placebo group (EG + starch) encountered growth retardation, with their body weights slowly increasing, expressed as 160.63 ± 23.06 g, compared with 179.63 ± 13.41 g in normal rats (p < 0.001). Conclusion: ZLT reduced the severity of CaOx crystallization and slowed down the body weight loss effects. Therefore, the traditional Chinese medicine herbal formula ZLT may be an effective reagent for renal stone prophylaxis. Although the mechanism of ZLT in crystal inhibition remains unclear, macromolecules may be involved.

[1]  V. Scheid,et al.  Chinese Herbal Medicine. Formulas & Strategies , 2009 .

[2]  V. Scheid,et al.  Comprar Chinese Herbal Medicine: Formulas & Strategies | V Scheid | 9780939616671 | Eastland , 2009 .

[3]  Fuu-Jen Tsai,et al.  A traditional Chinese herbal antilithic formula, Wulingsan, effectively prevents the renal deposition of calcium oxalate crystal in ethylene glycol-fed rats , 2008, Urological Research.

[4]  Wen-Chi Chen,et al.  Wu-Ling-San formula inhibits the crystallization of calcium oxalate in vitro. , 2006, The American journal of Chinese medicine.

[5]  Saeed R. Khan,et al.  Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxy-L-proline. , 2006, Kidney international.

[6]  Marguerite Hatch,et al.  Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats. , 2005, American journal of physiology. Renal physiology.

[7]  S. A. Ansari,et al.  In vitro inhibition and dissolution of calcium oxalate by edible plant Trianthema monogyna and pulse Macrotyloma uniflorum extracts , 2005 .

[8]  Wu Ji-zhou.  Analysis of Active Ingredients in Alisma orientalis (Sam.)Juze Extract for Inhibiting Formation of Urinary Oxalate Calcium Calculi by 2D NMR , 2005 .

[9]  A. Evan,et al.  Nephrolithiasis and nephrocalcinosis in rats with small bowel resection , 2005, Urological Research.

[10]  刘继红,et al.  Effect of alisma orientalis extract on renal stone formation and the expression of inter-alpha-trypsin inhibitor in rat urolithiasis model , 2004 .

[11]  M. Resnick,et al.  Minipump induced hyperoxaluria and crystal deposition in rats: a model for calcium oxalate urolithiasis. , 2004, The Journal of urology.

[12]  Zhou Si-wei.  Effect of alisma orientalis extract on renal stone formation and the expression of inter-alpha-trypsin inhibitor in rat urolithiasis model , 2004 .

[13]  R. Tawashi,et al.  Calcium oxalate crystal formation in the kidneys of rats injected with 4-hydroxy-L-proline , 2004, Urological Research.

[14]  Wang Shaya.  Influence of Rhizoma Alismatis on Inhibition of Renal Stone Formation , 2003 .

[15]  N. Schor,et al.  The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation , 2002, BJU international.

[16]  N. Yamanaka,et al.  Effectiveness of a traditional Chinese medicine, Wulingsan, in suppressing the development of nephrocalcinosis induced by a high phosphorus diet in young rats , 2001, Medical Electron Microscopy.

[17]  Jong‐Khing Huang,et al.  Combined Use of 30% Lactose Rich Diet and 1% Ethylene Glycol: A New Animal Model for Study of Urolithiasis , 2000 .

[18]  F. Atmani,et al.  Effects of an extract from Herniaria hirsuta on calcium oxalate crystallization in vitro , 2000, BJU international.

[19]  S. Nomura,et al.  The effect of takusha, a kampo medicine, on renal stone formation and osteopontin expression in a rat urolithiasis model , 1999, Urological Research.

[20]  Koji Suzuki,et al.  FORMATION AND GROWTH INHIBITION OF CALCIUM OXALATE CRYSTALS BY TAKUSHA (ALISMATIS RHIZOMA) , 1999 .

[21]  O. Miyake,et al.  [Effect of chorei-to and gorei-san on calcium oxalate crystallization in human urine]. , 1998, Hinyokika kiyo. Acta urologica Japonica.

[22]  M. Daudon,et al.  A stable animal model of diet-induced calcium oxalate crystalluria , 1998, Urological Research.

[23]  S. Yamaguchi,et al.  THE INHIBITORY EFFECT OF KAMPOU EXTRACTS ON IN VITRO CALCIUM OXALATE CRYSTALLIZATION AND IN VIVO STONE FORMATION IN AN ANIMAL MODEL , 1995, International journal of urology : official journal of the Japanese Urological Association.

[24]  W. Huang,et al.  Determinant role of testosterone in the pathogenesis of urolithiasis in rats. , 1992, The Journal of urology.

[25]  Jong‐Khing Huang,et al.  Characterization of Ethylene Glycol-Induced Urolithiasis Model in Rats , 1991 .

[26]  W. Kriz,et al.  Nephrocalcinosis in the Kidney of the Rat on Atherogenic Diet and the Effect of Calcium Antagonists (Nifedipine) , 1988 .

[27]  B. Finlayson,et al.  Experimental calcium oxalate nephrolithiasis in the rat. Role of the renal papilla. , 1982, The American journal of pathology.