, Volume 19, Issue 3, pp 119–125 | Cite as

Investigating the Protective Effects of Astragalus Membranaceus on Nephrotoxicity in Cyclosporine A-treated Rats



The immunosuppressive drug, cyclosporine A (CsA), has been used in patients who were treated for immune diseases and in transplant patients. However, nephrotoxicity due to CsA, remains an important clinical challenge. Although the mechanisms of nephrotoxicity are far from clear, notwithstanding there is evidence that suggests the role of oxidative stress in its pathogenesis. This study was conducted to investigate the protective effect of the Chinese herbal medicine, astragalus membranaceus (AM), in CsA-induced nephrotoxicity in a rat model. Adult Sprague–Dawley rats were treated with olive oil, CsA (25 mg/kg/bw), AM (5 mg/kg/bw), CsA plus AM for 30 days. Renal function, Malondialdehyde (MDA) levels were measured and histopathology, and Immunohistochemical staining for Endothelin was performed. In this study, CsA caused a significant deterioration in renal function, morphology, and also induced oxidative stress, as indicated by increased renal MDA. Administration of AM along with CsA improved the functional and histological parameters of the kidneys, and counteracted the oxidative stress induced by CsA. These results suggested that AM has a protective potential in experimental CsA nephrotoxicity.


Astragalus membranaceus cyclosporine A nephrotoxicity endothelin rat 


  1. 1.
    Mason J. The pathophysiology of sandimmun (cyclosporine) in man and animals. Pediatr Nephrol. 1990;4:554–74.CrossRefPubMedGoogle Scholar
  2. 2.
    Khan M, Shobha JC, Mohan IK, Rao Naidu MU, Prayag A, Kutala VK. Spirulina attenuates cyclosporine-induced nephrotoxicity in rats. J Appl Toxicol. 2006;26(5):444–51.CrossRefPubMedGoogle Scholar
  3. 3.
    Rezzani R, Rodella L, Bianchi R. Induction of endothelin in rat kidney after cyclosporine A treatment. Acta Histochem. 2001;103:423–31.CrossRefPubMedGoogle Scholar
  4. 4.
    Lanese DM, Conger JD. Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles. J Clin Invest. 1993;91:2144–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Serino F, Grevel J, Napoli KL, Kahan BD, Strobel HW. Oxygen radical formation by the cytochrome P450 system as a cellular mechanism for cyclosporine toxicity. Transplant Proc. 1994;26:2916–7.PubMedGoogle Scholar
  6. 6.
    Amore A, Gianoglio B, Ghigo D, Peruzzi L, Porcellini MG, Bussolino F, et al. A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine. Kidney Int. 1995;47:1507–14.CrossRefPubMedGoogle Scholar
  7. 7.
    Dusting GJ, Akita K, Hickey H, Smith M, Gurevich V. Cyclosporine A and tacrolimus (FK506) suppress expression of inducible nitric oxide synthase in vitro by different mechanisms. Br J Pharmacol. 1999;128:337–44.CrossRefPubMedGoogle Scholar
  8. 8.
    Buetler TM, Cottet-Maire F, Krauskopf A, Ruegg UT. Does cyclosporine A generate free radicals? Trends Pharmacol Sci. 2000;21:288.CrossRefPubMedGoogle Scholar
  9. 9.
    Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. Semin Nephrol. 2003;23(5):365–76.CrossRefGoogle Scholar
  10. 10.
    Cho WC, Leung KN. In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. J Ethnopharmacol. 2007;113:132–41.CrossRefPubMedGoogle Scholar
  11. 11.
    Su L, Chen YC, Hu JD, et al. Comparisons between different doses of Astragalus membranaceus and Salvia miltiorrhiza in rats proteinuria. Chinese Journal of New Drugs and Clinical Remedies. 2000;19:205–8.Google Scholar
  12. 12.
    Shi JF, Zhu HW, Zhang C, et al. Therapeutic effect of astragalus on patients with chronic glomerulonephritis. Acta Medicinalis Secondae Shanghai. 2002;22:245–8.Google Scholar
  13. 13.
    Block KI, Mead MN. Immune system effects of echinacea, ginseng, and astragalus: a review. Integr Cancer Ther. 2003;2(3):247–67.CrossRefPubMedGoogle Scholar
  14. 14.
    Taixiang W, Munro AJ, Guanjian L. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005;25(1):CD004540.Google Scholar
  15. 15.
    Farthing MJ, Clark ML. Nature of the toxicity of cyclosporine A in the rat. Biochem Pharmacol. 1981;30(24):3311–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A. N-acetylcysteine attenuate cyclosporine-induced nephrotoxicity in rats. Nephrol Dial Transplant. 1999;14(4):923–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Amudha G, Josephine A, Varalakshmi P. Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A. Clin Chim Acta. 2006;372(1–2):134–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Hagar HH, El Etter E, Arafa M. Taurine attenuates hypertension and renal dysfunction induced by cyclosporine A in rats. Clin Exp Pharmacol Physiol. 2006;33(3):189–96.CrossRefPubMedGoogle Scholar
  19. 19.
    Caline RY, White DJG, Thiru S, Evans DB, MCMaster P, Dunn DC, et al. Cyclosporine A in patients reciving renal allografts from cadaver donors. Lancet. 1978;II:1323–7.CrossRefGoogle Scholar
  20. 20.
    Wongmekiat O, Leelarugrayub N, Thamprasert K. Beneficial effect of shallot (Allium ascalonicum L.) extract on cyclosporine nephrotoxicity in rats. Food Chem Toxicol. 2008;46:1844–50.CrossRefPubMedGoogle Scholar
  21. 21.
    Parra CT, Conejo Garcia JR, Carballo AF, de Arriba G. Antioxidant nutrients protect against cyclosporine A nephrotoxicity. Toxicology. 2003;189:99–111.CrossRefGoogle Scholar
  22. 22.
    Zhong Z, Connor HD, Yin M, Moss N, Mason RP, Bunzendahl H, et al. Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney. Mol Pharmacol. 1999;56(3):455–63.PubMedGoogle Scholar
  23. 23.
    Yoshimura R, Yoshimura N, Nakatani T, Kusunose E, Yamaguchi T, Oka T, et al. The effect of cyclosporine on renal microsomal cytochrome P-450 system. Clin Nephrol. 1993;40:339–45.PubMedGoogle Scholar
  24. 24.
    Freeman BA, Crapho JD. Biology of disease: free radical and tissue injury. Lab Invest. 1982;47:412–26.PubMedGoogle Scholar
  25. 25.
    Anjaneyulu M, Tirkey N, Chopra K. Attenuation of cyclosporine-induced renal dysfunction by catechin: possible antioxidant mechanism. Ren Fail. 2003;25:691–707.CrossRefPubMedGoogle Scholar
  26. 26.
    Padi SS, Chopra K. Salvage of cyclosporine A-induced oxidative stress and renal dysfunction by carvedilol. Nephron. 2002;92(3):685–92.CrossRefPubMedGoogle Scholar
  27. 27.
    Nakahama H. Stimulatory effect of cyclosporine A on endothelin secretion by a cultured renal epithelial cell line, LLC-PK cells. Eur J Pharmacol. 1990;180:191–2.CrossRefPubMedGoogle Scholar
  28. 28.
    Textor SC, Burnett Jr JC, Romero JC, et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation. Kidney Int. 1995;47:1426–33.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Molecular Biology Department, Genetic Engineering and Biotechnology Research InstituteMinufiya UniversitySadat CityEgypt

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