, Volume 42, Issue 2, pp 97–103 | Cite as

Antioxidants inhibition of high plasma androgenic markers in the pathogenesis of ethylene glycol (EG)-induced nephrolithiasis in Wistar rats

  • Mohammad Reza Naghii
  • Mahmood Mofid
  • Mehdi Hedayati
  • Kazem Khalagi
Original Paper


The association between serum gonadal steroids and urolithiasis in males received only limited attention. Calcium oxalate urolithiasis is induced by administration of ethylene glycol in drinking water. It appears that the administration of natural antioxidants has been used to protect against nephrolithiasis in human and experimental animals. The purpose is to study the potential role of antioxidants as inhibitors of high plasma androgenic markers or hyperandrogenicity in the pathogenesis of ethylene glycol-induced nephrolithiasis in Wistar rats. Male Wistar rats were studied in 4-week period. Group 1 (control) was fed a standard commercial diet. Group 2 received the same diet with 0.5 % of ethylene glycol. Group 3 received EG plus the diet and water added with antioxidant nutrients and lime juice as the dietary source of citrate. Group 4 and Group 5 were treated similar to Group 2 and Group 3 with 0.75 % of ethylene glycol. For antioxidant supplementation, the standard diet enriched with 4,000.0 μg vitamin E and 1,500.0 IU vitamin A for each rat per day added to the diet once a week, and provided daily with 5.0 mg vitamin C, 400.0 μg vitamin B6, 20.0 μg selenium, 12.0 mg zinc, and 2.0 mg boron for each rat per day in their drinking water. After treatment period, collection of blood was performed and kidneys were removed and used for histopathological examination. The results based on various assays, measuring size of crystal deposition, and histological examinations showed that high concentration of androgens acts as promoter for the formation of renal calculi due to ethylene glycol consumption and the inhibitory role of antioxidant complex in the formation of renal calculi disease. Data revealed that the size and the mean number of crystal deposits determined in EG 0.75 % treated groups (G4) were significantly higher than the EG-treated groups, added with antioxidant nutrients and lime juice (G5). The mean concentration of androgens in Group 4 increased after EG 0.75 % administration, and decreased after antioxidants supplementation in Group 5. Elevated concentration of androgens (as promoters of the formation of renal calculi) as a result of EG consumption and their decreasing following antioxidant supplementations along with the slight decrease in malondialdehyde level provides a scientific rational for preventive and treatment roles of antioxidant nutrient complex in kidney stone disease.


Ethylene glycol Calcium oxalate urolithiasis Antioxidants Androgens Wistar rats 


Conflict of interest

There is no conflict of interest.


  1. 1.
    Curhan GC (2007) Epidemiology of stone disease. Urol Clin North Am 34:287–293PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Fan J, Glass MA, Chandhoke PS (1989) Effect of castration and finasteride on urinary oxalate excretion in male rats. Urol Res 26:71–75CrossRefGoogle Scholar
  3. 3.
    Patel P, Patel M, Saralai M, Gandhi T (2012) Antiurolithiatic effects of Solanum xanthocarpum fruit extract on ethylene-glycol-induced nephrolithiasis in rats. J Young Pharm 4:164–170PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Lee YH, Huang WC, Huang JK, Chang LS (1996) Testosterone enhances whereas estrogen inhibits calcium oxalate stone formation in ethylene glycol treated rats. J Urol 156:502–505PubMedCrossRefGoogle Scholar
  5. 5.
    Yoshioka I, Tsujihata M, Momohara C, Akanae W, Nonomura N, Okuyama A (2010) Effect of sex hormones on crystal formation in a stone-forming rat model. Urology 75:907–913PubMedCrossRefGoogle Scholar
  6. 6.
    Yagisawa T, Ito F, Osaka Y, Amano H, Kobayashi C, Toma H (2001) The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis. J Urol 166:1078–1082PubMedCrossRefGoogle Scholar
  7. 7.
    Ozbek E (2012) Induction of oxidative stress in kidney. Int J Nephrol. doi: 10.1155/2012/465897 PubMedCentralPubMedGoogle Scholar
  8. 8.
    Naziroglu M, Karaoğlu A, Aksoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230PubMedCrossRefGoogle Scholar
  9. 9.
    Huang HS, Ma MC, Chen J (2009) Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney. Am J Physiol Renal Physiol 296:F34–F45PubMedCrossRefGoogle Scholar
  10. 10.
    Santhosh Kumar M, Selvam R (2003) Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats. J Nutr Biochem 14:306–313PubMedCrossRefGoogle Scholar
  11. 11.
    Bardaoui M, Sakly R, Neffat F, Najjar MF, El Hani A (2010) Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in rats. Exp Toxicol Pathol 62:573–576PubMedCrossRefGoogle Scholar
  12. 12.
    Selvam R (2002) Calcium oxalate stone disease: role of lipid peroxidation and antioxidants. Urol Res 30:35–47PubMedCrossRefGoogle Scholar
  13. 13.
    Ortiz-Alvarado O, Miyaoka R, Kriedberg C, Moeding A, Stessman M, Monga M (2011) Pyridoxine and dietary counseling for the management of idiopathic hyperoxaluria in stone-forming patients. Urology 77:1054–1058PubMedCrossRefGoogle Scholar
  14. 14.
    Atakan IH, Kaplan M, Seren G, Aktoz T, Gül H, Inci O (2007) Serum, urinary and stone zinc, iron, magnesium and copper levels in idiopathic calcium oxalate stone patients. Int Urol Nephrol 39:351–356PubMedCrossRefGoogle Scholar
  15. 15.
    Naghii MR, Einollahi B, Rostami Z (2012) Preliminary evidence hints at a protective role for boron in urolithiasis. J Altern Complement Med 18:207–209PubMedCrossRefGoogle Scholar
  16. 16.
    Touhami M, Laroubi A, Elhabazi K, Loubna F, Zrara I, Eljahiri Y et al (2007) Lemon juice has protective activity in a rat urolithiasis model. BMC Urol 7:18PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Travison TG, Araujo AB, Hall SA, McKinlay JB (2009) Temporal trends in testosterone levels and treatment in older men. Curr Opin Endocrinol Diabetes Obes 16:211–217PubMedCrossRefGoogle Scholar
  18. 18.
    Li JY, Zhou T, Gao X, Xu C, Sun Y, Peng Y et al (2010) Testosterone and androgen receptor in human nephrolithiasis. J Urol 184:2360–2363PubMedCrossRefGoogle Scholar
  19. 19.
    Finlayson B (1974) Symposium on renal lithiasis. Renal lithiasis in review. Urol Clin North Am 1:181–212PubMedGoogle Scholar
  20. 20.
    Curhan GC (1999) Epidemiologic evidence for the role of oxalate in idiopathic nephrolithiasis. J Endourol 13:629–631PubMedCrossRefGoogle Scholar
  21. 21.
    Fan J, Chandhoke PS, Grampsas SA (1999) Role of sex hormones in experimental calcium oxalate nephrolithiasis. J Am Soc Nephrol suppl 14:S376–S380Google Scholar
  22. 22.
    Naghii MR, Hedayati M (2010) Determinant role of gonadal sex hormones in the pathogenesis of urolithiasis in a male subject—a document for male predominancy (case study). Endocr Regul 44:143–146PubMedCrossRefGoogle Scholar
  23. 23.
    Watson JM, Shrewsberry AB, Taghechian S, Goodman M, Pattaras JG, Ritenour CW et al (2010) Serum testosterone may be associated with calcium oxalate urolithogenesis. J Endourol 24:1183–1187PubMedCrossRefGoogle Scholar
  24. 24.
    Shakhssalim N, Gilani KR, Parvin M, Torbati PM, Kashi AH, Azadvari M et al (2010) An assessment of parathyroid hormone, calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors. Urol Res 39:1–7PubMedCrossRefGoogle Scholar
  25. 25.
    Tothova L, Celec P, Ostatnikov D, Okuliarova M, Zeman M, Hodosy J (2012) Effect of exogenous testosterone on oxidative status of the testes in adult male rats. Andrologia. doi:  10.1111/and.12032

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mohammad Reza Naghii
    • 1
  • Mahmood Mofid
    • 2
  • Mehdi Hedayati
    • 3
  • Kazem Khalagi
    • 4
  1. 1.Department of Nutrition, Health School and Sport Physiology Research CenterBaqiyatallah (a.s.) University of Medical SciencesTehranIslamic Republic of Iran
  2. 2.Department of Anatomy, Faculty of MedicineBaqiyatallah (a.s.) University of Medical SciencesTehranIslamic Republic of Iran
  3. 3.Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIslamic Republic of Iran
  4. 4.Department of Epidemiology and Statistics, Health SchoolBaqiyatallah (a.s.) University of Medical SciencesTehranIslamic Republic of Iran

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