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Use of Antioxidants to Prevent Cyclosporine A Toxicity

  • Lee, Jin-Hwa (Dept. of Clinical Lab Science, Dongseo University)
  • Received : 2010.07.02
  • Accepted : 2010.08.11
  • Published : 2010.09.01

Abstract

Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS). In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA's adverse effects and therefore might help develop more effective CsA treatment regimens.

Keywords

References

  1. Al-Malki, A.L. and Moselhy, S.S. (2010). The protective effect of epicatchin against oxidative stress and nephrotoxicity in rats induced by cyclosporine. Hum. Exp. Toxicol., [Epub ahead of print].
  2. Amudha, G., Josephine, A., Sudhahar, V. and Varalakshmi, P.(2007). Protective effect of lipoic acid on oxidative and peroxidative damage in cyclosporine A-induced renal toxicity. Int.Immunopharmacol., 7, 1442-1449. https://doi.org/10.1016/j.intimp.2007.06.010
  3. Arnadottir, M., Hultberg, B., Vladov, V., Nilsson-Ehle, P. and Thysell, H. (1996). Hyperhomocysteinemia in cyclosporine-treatedrenal transplant recipients, Transplantation, 61, 509-512. https://doi.org/10.1097/00007890-199602150-00034
  4. Baid, S., Cosimi, A.B., Farrell, M.L., Schoenfeld, D.A., Feng, S.,Chung, R.T., Tolkoff-Rubin, N. and Pascual, M. (2001). Posttransplant diabetes mellitus in liver transplant recipients: risk factors, temporal relationship with hepatitis C virus allografthepatitis, and impact on mortality. Transplantation, 72, 1066-1072. https://doi.org/10.1097/00007890-200109270-00015
  5. Beckman, J.A., Creager, M.A. and Libby, P. (2002). Diabetes andatherosclerosis: epidemiology, pathophysiology, and management.JAMA, 287, 2570-2581. https://doi.org/10.1001/jama.287.19.2570
  6. Behforouz, N.C. and Wenger, C.D. (1988). Immunomodulation of murine leishmaniasis with cyclosporin A. Adv. Exp. Med. Biol., 239, 379-384. https://doi.org/10.1007/978-1-4757-5421-6_36
  7. Bilchick, K.C., Henrikson, C.A., Skojec, D., Kasper, E.K. andBlumenthal, R.S. (2004). Treatment of hyperlipidemia in cardiactransplant recipients. Am. Heart J., 148, 200-210. https://doi.org/10.1016/j.ahj.2004.03.050
  8. Boots, J.M., Christiaans, M.H. and van Hooff, J.P. (2004). Effect of immunosuppressive agents onlong-term survival of renal transplant recipients: focusonthe cardiovascular risk. Drugs., 64, 2047-2073. https://doi.org/10.2165/00003495-200464180-00004
  9. Calne, R.Y., White, D.J., Thiru, S., Evans, D.B., McMaster, P.,Dunn, D.C., Craddock, G.N., Pentlow, B.D. Rolles, K. (1978).Cyclosporin A in patients receiving renal allografts fromcadaver donors. Lancet, 2, 1323-1327.
  10. Capasso, G., Di Gennaro, C.I., Della Ragione, F., Manna, C., Ciarcia, R., Florio, S., Perna, A., Pollastro, R.M., Damiano, S., Mazzoni, O., Galletti, P. and Zappia, V. (2008). In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine nephrotoxicity in rats. Nephrol Dial Transplant., 23, 1186-1195.
  11. Chen, C., Jeon, H., Johnston, T.D., Gedaly, R., McHugh, P.P. andRanjan, D. (2008). Cyclosporin A-induced lipid and proteinoxidation in human B-cells and in Epstein-Barr virus-infectedB-cells is prevented by antioxidants. J. Invest. Surg., 21, 201-208. https://doi.org/10.1080/08941930802262223
  12. de Arriba, G., de Hornedo, J.P., Rubio, S.R., Fernandez, M.C.,Martínez, S.B., Camarero, M.M. and Cid, T.P. (2009). Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells. Toxicol. Appl. Pharmacol.,239, 241-250. https://doi.org/10.1016/j.taap.2009.05.028
  13. Deby, C. and Goutier, R. (1990). New perspectives on the biochemistry of superoxide anion and the efficiency of superoxide dismutases. Biochem.Pharmacol., 39, 399-405. https://doi.org/10.1016/0006-2952(90)90043-K
  14. de Mattos, A.M., Olyaei, A.J. and Bennett, W.M. (2000). Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am. J. Kidney Dis., 35, 333-346 https://doi.org/10.1016/S0272-6386(00)70348-9
  15. Diao, T.J., Yuan, T.Y. and Li, Y.L. (2002). Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation. World J. Gastroenterol., 8, 746-751. https://doi.org/10.3748/wjg.v8.i4.746
  16. Doyle, V., Virji, S. and Crompton, M. (1999). Evidence that cyclophilin-A protects cells against oxidative stress. Biochem. J. 341,127-132. https://doi.org/10.1042/0264-6021:3410127
  17. Hong, F., Lee, J., Song, J.W., Lee, S.J., Ahn, H., Cho, J.J., Ha, J.and Kim, S.S. (2002). Cyclosporin A blocks muscle differentiation by inducing oxidative stress and inhibiting the peptidylprolyl-cis–trans isomerase activity of cyclophilin A: cyclophilin A protects myoblasts from cyclosporin A-induced cytotoxicity.FASEB J., 16, 1633-1635. https://doi.org/10.1096/fj.02-0060fje
  18. Durak, I., Karabacak, H.I., Buyukkocak, S., Cimen, M.Y., Kacmaz,M., Omeroglu, E. and Ozturk, H.S. (1998). Impaired antioxidant defense system in the kidney tissues from rabbits treated with cyclosporine. Protective effects of vitamins E and C. Nephron, 78, 207-211.
  19. Ebru, U., Burak, U., Yusuf, S., Reyhan, B., Arif, K., Faruk, T.H.,Emin, M., Aydin, K., Atilla, I.I., Semsettin, S.nand Kemal, E.(2008). Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats. Basic Clin Pharmacol. Toxicol., 103, 574-580. https://doi.org/10.1111/j.1742-7843.2008.00313.x
  20. Erlanger, B.F. (1992). Do we know the site of action of cyclosporin? Immunol. Today, 13, 487-490. https://doi.org/10.1016/0167-5699(92)90023-Z
  21. Fraser, A., Veale, D.J. and Emery, P. (2003). Cyclosporin treatment in psoriatic arthritis: a cause of severe leg pain. Ann. Rheum. Dis., 62, 489. https://doi.org/10.1136/ard.62.5.489
  22. Fridovich, I. (1978). The biology of oxygen radicals. Science, 201,875-880. https://doi.org/10.1126/science.210504
  23. Gokce, A., Oktar, S., Yonden, Z., Aydin, M., Ilhan, S., Ozkan, O.V., Davarci, M. and Yalcinkaya, F.R. (2009). Protective effect of caffeic acid phenethyl ester on cyclosporine A-induced nephrotoxicity in rats. Ren Fail., 31, 843-847. https://doi.org/10.3109/08860220903137517
  24. Halliwell, B. and Gutteridge, J.M.C. (1999). Free Radicals in Biology and Medicine, Oxford University Press.
  25. Hancock, J.T., Desikan, R. and Neill, S.J. (2001). Role of reactive oxygen species in cell signalling pathways. Biochemical Society Transactions, pp. 345-350.
  26. Herrero, J.I., Quiroga, J., Sangro, B., Beloqui, O., Pardo, F., Cienfuegos, J.A. and Prieto, J. (2000). Hyperhomocysteinemia inliver transplant recipients: prevalence and multivariate analysis of predisposing factors. Liver Transplant., 6, 614-618. https://doi.org/10.1053/jlts.2000.7571
  27. Heydendael, V.M., Spuls, P.I., Opmeer, B.C., de Borgie, C.A., Reitsma, J.B., Goldschmidt, W.F., Bossuyt, P.M., Bos, J.D. and de Rie, M.A. (2003). Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl. J. Med., 349,658-665. https://doi.org/10.1056/NEJMoa021359
  28. Hjelmesaeth, J., Asberg, A., Muller, F., Hartmann, A. and Jenssen,T. (2005). New-onset posttransplantation diabetes mellitus:insulin resistance or insulinopenia? Impact of immunosuppressive drugs, cytomegalovirus and hepatitis C virus infection. Curr. Diabetes Rev., 1, 1-10. https://doi.org/10.2174/1573399052952604
  29. Ho, S., Clipstone, N., Timmermann, L., Northrop, J., Graef, I., Fiorentino, D., Nourse, J. and Crabtree, G.R. (1996). The mechanism of action of cyclosporin A and FK506. Clin. Immunol.Immunopathol., 80, S40-S45. https://doi.org/10.1006/clin.1996.0140
  30. Inselmann, G., Barth, A., Engemann, R. and Heidemann, H.T.(1991). Cyclosporin-A induced lipid peroxidation in humanliver microsomes and its influence on cytochrome P-450. Eur.J. Clin. Invest., 21, 461-465. https://doi.org/10.1111/j.1365-2362.1991.tb01395.x
  31. Inselmann, G., Lawerenz, H.U., Nellessen, U. and Heidemann,H.T. (1994). Enhancement of cyclosporin A induced hepatoand nephrotoxicity by glutathione depletion. Eur. J. Clin. Invest., 24, 355-359. https://doi.org/10.1111/j.1365-2362.1994.tb01097.x
  32. Ischiropoulos, H., Gow, A., Thom, S.R., Kooy, N.W., Royall, J.A.and Crow, J.P. (1999). Detection of reactive nitrogen speciesusing 2,7-dichlorodihydrofluorescein and dihydrorhodamine123. In Methods in Enzymology: Oxygen Radicals in BiologicalSystem (Packer, L., ed.) Academic Press, (Part D) (Vol. 301)pp. 367-373.
  33. Jones, O.T.G. and Hancock, J.T. (2000). Free Radicals in Inflammation (P.G. Winyard, D.R. Blake, C.H. Evans, Eds.), Birkha, Switzerland, pp. 21-46.
  34. Josephine, A., Amudha, G., Veena, C.K., Preetha, S.P. and Varalakshmi, P. (2007). Oxidative and nitrosative stress mediated renal cellular damage induced by cyclosporine A: role of sulphated polysaccharides. Biol. Pharm. Bull., 30, 1254-1259. https://doi.org/10.1248/bpb.30.1254
  35. Josephine, A., Nithya, K., Amudha, G., Veena, C.K., Preetha, S.P.and Varalakshmi, P. (2008). Role of sulphated polysaccharides from sargassum wightii in cyclosporine A-induced oxidative liver injury in rats. BMC Pharmacol., 8, 4.
  36. Josephine, A., Veena, C.K., Amudha, G., Preetha, S.P. and Varalakshmi, P. (2006). Evaluating the effect of sulphated polysaccharides on cyclosporine a induced oxidative renal injury. Mol. Cell. Biochem., 287, 101-108. https://doi.org/10.1007/s11010-005-9081-7
  37. Jung, J.Y., Kang, G.C., Jeong, Y.J., Kim, S.H., Kwak, Y.G. andKim, W.J. (2009). Proteomic analysis in cyclosporin A-inducedovergrowth of human gingival fibroblasts. Biol. Pharm. Bull.,32, 1480-1485. https://doi.org/10.1248/bpb.32.1480
  38. Kobashigawa, J.A. and Kasiske, B.L. (1997). Hyperlipidemia insolid organ transplantation. Transplantation, 63, 331-338. https://doi.org/10.1097/00007890-199702150-00001
  39. Krauskopf, A., Buetler, T.M., Nguyen, N.S., ,Macé, K. and Ruegg, U.T. (2002). Cyclosporin A-induced free radical generation is not mediated by cytochrome P-450. Br. J. Pharmacol., 135, 977-986. https://doi.org/10.1038/sj.bjp.0704544
  40. Kumar, M.S., Xiao, S.G., Fyfe, B., Sierka, D., Heifets, M., Moritz,M.J., Saeed, M.I. and Kumar, A. (2005). Steroid avoidance in renal transplantation using basiliximab induction,cyclosporinebased immunosuppression and protocol biopsies. Clin Transplant., 19, 61-69. https://doi.org/10.1111/j.1399-0012.2004.00298.x
  41. Langford, C.A., Klippel, J.H., Balow, J.E., James, S.P. and Sneller,M.C. (1998a). Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 1: rheumatologic and renal diseases. Ann. Intern. Med., 128, 1021-1028. https://doi.org/10.7326/0003-4819-128-12_Part_1-199806150-00012
  42. Langford, C.A., Klippel, J.H., Balow, J.E., James, S.P. and Sneller,M.C. (1998b). Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2: inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity. Ann.Intern. Med., 129, 49-58. https://doi.org/10.7326/0003-4819-129-1-199807010-00012
  43. L’Azou, B., Medina, J., Frieauff, W., Cordier, A., Cambar, J. and Wolf, A. (1999). In vitro models to study mechanisms involved in cyclosporine A-mediated glomerular contraction. Arch. Toxicol.,73, 337-345. https://doi.org/10.1007/s002040050627
  44. Leong, A.C., Yong, J. and Salama, N. (2010). Lymphoproliferativedisorder of nasopharynx after long-standing cyclosporin therapy for psoriatic arthritis. J. Laryngol. Otol., 7, 1-3.
  45. Lichtiger, S., Present, D.H., Kornbluth, A., Gelernt, I., Bauer, J.,Galler, G., Michelassi, F. and Hanauer, S. (1994). Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl.J. Med., 330, 1841-1845. https://doi.org/10.1056/NEJM199406303302601
  46. Louie, B., Rajamahanty, S., Pyo, P., Choudhury, M. and Konno, S.(2010). Mode of cytotoxic action of nephrotoxic agents:oxidativestress and glutathione-dependent enzyme. BJU Int., 105,264-268. https://doi.org/10.1111/j.1464-410X.2009.08657.x
  47. Malyszko, J., Malyszko, J.S., Pawlak, K. and Mysliwiec, M.(1996). The coagulo-lytic system and endothelial function in cyclosporine-treated kidney allograft recipients. Transplantation,62, 828-830. https://doi.org/10.1097/00007890-199609270-00021
  48. Marchetti, P. (2004). New-onset diabetes after transplantation. J.Heart Lung Transplant., 23, S194-S201. https://doi.org/10.1016/j.healun.2004.03.007
  49. Mason, J. (1990). The pathophysiology of Sandimmune (cyclosporine) in man and animals. Pediatr. Nephrol., 4, 686-704. https://doi.org/10.1007/BF00858649
  50. McGrath, L.T., Treacy, R., McClean, E. and Brown, J.H. (1997).Oxidative stress in cyclosporin and azathioprine treated renaltransplant patients. Clin. Chim. Acta, 264, 1-12. https://doi.org/10.1016/S0009-8981(97)00088-0
  51. Moien-Afshari, F., McManus, B.M. and Laher, I. (2003). Immunosuppression and transplant vascular disease: benefits andadverse effects. Pharmacol. Ther., 100, 141-156. https://doi.org/10.1016/j.pharmthera.2003.08.002
  52. Mostafavi-Pour, Z., Zal, F., Monabati, A. and Vessal, M. (2008).Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats. Hepatol. Res., 38, 385-392. https://doi.org/10.1111/j.1872-034X.2007.00273.x
  53. Mourad, G., Vela, C., Ribstein, J. and Mimran, A. (1998). Longterm improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy. Transplantation, 65, 661-667. https://doi.org/10.1097/00007890-199803150-00010
  54. Myers, B.D., Sibley, R., Newton, L., Tomlanovich, S.J., Boshkos,C., Stinson, E., Luetscher, J.A., Whitney, D.J., Krasny, D. andCoplon, N.S. (1988). The long-term course of cyclosporineassociated chronic nephropathy. Kidney Int., 33, 590-600. https://doi.org/10.1038/ki.1988.38
  55. Nankivell, B.J., Borrows, R.J., Fung, C.L., O’Connell, P.J., Allen,R.D. and Chapman, J.R. (2003). The natural history of chronic allograft nephropathy. N Engl. J. Med., 349, 2326-2333. https://doi.org/10.1056/NEJMoa020009
  56. Olyaei, A.J., de Mattos, A.M. and Bennett, W.M. (2001). Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr. Opin. Crit. Care., 7, 384-389. https://doi.org/10.1097/00075198-200112000-00003
  57. Pari, L. and Sivasankari, R. (2008). Effect of ellagic acid oncyclosporine A-induced oxidative damage in the liver of rats.Fundam Clin Pharmacol., 22, 395-401. https://doi.org/10.1111/j.1472-8206.2008.00609.x
  58. Parra Cid, T., Conejo Garcia, J.R., Carballo Alvarez, F. and deArriba, G. (2003). Antioxidant nutrients protect against cyclosporine A nephrotoxicity. Toxicology, 189, 99-111. https://doi.org/10.1016/S0300-483X(03)00156-2
  59. Parra, T., de Arriba, G., Arribas, I., Perez de Lema, G., Rodriguez-Puyol, D. and Rodriguez-Puyol, M. (1998a). Cyclosporine A nephrotoxicity: role of thromboxane and reactive oxygen species. J. Lab. Clin. Med., 131, 63-70. https://doi.org/10.1016/S0022-2143(98)90078-6
  60. Parra, T., de Arriba, G., Conejo, J.R., Cantero, M., Arribas, I.,Rodriguez-Puyol, D., Rodriguez-Puyol, M. and Carballo, F.,(1998b). Cyclosporine increases local glomerular synthesis ofreactive oxygen species in rats: effect of vitamin E on cyclosporine nephrotoxicity. Transplantation, 66, 1325-1329. https://doi.org/10.1097/00007890-199811270-00011
  61. Pascual, M., Theruvath, T., Kawai, T., Tolkoff-Rubin, N. andCosimi, A.B. (2002). Strategies to improve long-term outcomesafter renal transplantation. N Engl. J. Med., 346, 580-590. https://doi.org/10.1056/NEJMra011295
  62. Perez de Lema, G., Arribas-Gomez, I., Ruiz-Gines, J.A., de Arriba,G., Prieto, A., Rodriguez-Puyol, D. and Rodriguez-Puyol, M.,(1997). Reactive oxygen species mediate the effects ofcyclosporine A on human cultured mesangial cells. Transplant.Proc., 29, 1241-1243. https://doi.org/10.1016/S0041-1345(96)00482-4
  63. Perez de Lema, G., Arribas, I., Prieto, A., Parra, T., de Arriba,G., Rodríguez-Puyol, D. and Rodríguez-Puyol, M. (1998).Cyclosporin A-induced hydrogen peroxide synthesis by culturedhuman mesangial cells is blocked by exogenous antioxidants.Life Sci., 62, 1745-1753. https://doi.org/10.1016/S0024-3205(98)00136-2
  64. Pickrell, M.D., Sawers, R. and Michael, J. (1988). Pregnancy after renal transplantation: severe intrauterine growth retardation during treatment with cyclosporin A. Br. Med. J., 19, 825.
  65. Racusen, L.C., Kone, B.C. and Solez, K. (1987). Early renal pathophysiology in an acute model of cyclosporine nephrotoxicityin rats. Ren Fail., 10, 29-37. https://doi.org/10.3109/08860228709047642
  66. Reis, F., Rocha-Pereira, P., Teixeira de Lemos, E., Parada, B., Baptista,S., Figueiredo, A., Santos-Silva, A., Costa-Almeida, C.,Mota, A. and Teixeira, F. (2007). Oxidative stress in cyclosporine-induced hypertension: evidence of beneficial effects or tolerance development with nitrate therapy. Transplant Proc., 39,2494-500. https://doi.org/10.1016/j.transproceed.2007.07.030
  67. Rezzani, R. (2004). Cyclosporine A and adverse effects on organs:histochemical studies. Prog. Histochem. Cytochem., 39, 85-128. https://doi.org/10.1016/j.proghi.2004.04.001
  68. Rezzani, R. (2006). Exploring cyclosporine A-side effects and the protective role-played by antioxidants: the morphological and immunohistochemical studies. Histol Histopathol., 21, 301-16.
  69. Rezzani, R., Rodella, L.F., Fraschini, F., Gasco, M.R., Demartini,G., Musicanti, C. and Reiter, R.J. (2009). Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage. J. Pineal. Res., 46, 255-261. https://doi.org/10.1111/j.1600-079X.2008.00651.x
  70. Romero, M., Garcia-Monzon, C., Clemente, G., Salcedo, M.,Alvarez, E., Majano, P.L. and Moreno-Otero, R. (2001). Intrahepatic expression of inducible nitric oxide synthase in acute liver allograft rejection: evidence of modulation by corticosteroids. Liver-Transplantation., 7, 16-21. https://doi.org/10.1053/jlts.2001.20779
  71. Shaw, K.T., Ho, A.M., Raghavan, A., Kim, J., Jain, J., Park, J.,Sharma, S., Rao, A. and Hogan, P.G. (1995). Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proc. Natl. Acad.Sci. USA, 92, 11205-11209. https://doi.org/10.1073/pnas.92.24.11205
  72. Shen, S.Y., Weir, M.R., Revie, D.R., Dagher, F.J., Bentley, F.R.and Chretien, P.B. (1987). Differentiation of acute rejection from acute cyclosporine nephrotoxicity in renal transplants peripheral T cell subset counts. Transplant Proc., 19, 1776-1779.
  73. Markell, M., Armenti, V., Danovitch, G. and Sumrani, N. (1994).Hyperlipidemia and glucose intolerance in the post-renal transplant patient. J. Am. Soc. Nephrol., 4, S37-S47.
  74. Stallone, G., Infante, B., Schena, A., Di Paolo, S., Grandaliano, G.,Gesualdo, L. and Schena, F.P. (2004). Cardiovascular risk and renal transplantation. G. Ital.Nefrol., 21, 144-155.
  75. Suthanthiran, M., Morris, R.E. and Strom, T.B. (1996). Immunosuppressants:cellular and molecular mechanisms of action. Am.J. Kidney Dis., 28, 159-172. https://doi.org/10.1016/S0272-6386(96)90297-8
  76. Taylor, A.L., Watson, C.J. and Bradley, J.A. (2005). Immunosuppressive agents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit. Rev. Oncol. Hematol., 56,23-46. https://doi.org/10.1016/j.critrevonc.2005.03.012
  77. ten Brinke, A., Zwinderman, A.H., Sterk, P.J., Rabe, K.F. and Bel, E.H. (2004). "Refractory" eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am. J. Respir. Crit. Care Med., 170, 601-605. https://doi.org/10.1164/rccm.200404-440OC
  78. Tugwell, P., Pincus, T., Yocum, D., Stein, M., Gluck, O., Kraag,G., McKendry, R., Tesser, J., Baker, P. and Wells, G. (1995).Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The methotrexate-cyclosporine combination study group. N Engl J Med., 333, 137-141. https://doi.org/10.1056/NEJM199507203330301
  79. Watkins, P.B. (1990). The role of cytochromes P-450 in cyclosporine metabolism. J. Am. Acad. Dermatol., 23, 1301-1309. https://doi.org/10.1016/0190-9622(90)70358-O
  80. Weber, A.J., Soong, G., Bryan, R., Saba, S. and Prince, A. (2001).Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function. Am. J.Physiol. Lung Cell. Mol. Physiol., 281, L71-L78. https://doi.org/10.1152/ajplung.2001.281.1.L71
  81. Yuce, A., Atessahin, A. and Ceribasi, A.O. (2008). Amelioration of cyclosporine A-induced renal, hepatic and cardiac damages by ellagic acid in rats. Basic Clin. Pharmacol. Toxicol., 103, 186-191. https://doi.org/10.1111/j.1742-7843.2008.00284.x
  82. Young, B.A., Burdmann, E.A., Johnson, R.J., Alpers, C.E., Giachelli,. C. M., Eng, E., Andoh, T., Bennett, W.M. and Couser, W.G.(1995a). Cellular proliferation and macrophage influx precede interstitial fibrosis in cyclosporine nephrotoxicity. Kidney Int.,48, 439-448. https://doi.org/10.1038/ki.1995.312
  83. Young, B.A., Burdmann, E.A., Johnson, R.J., Andoh, T., Bennett,W.M., Couser, W.G. and Alpers, C.E. (1995b). Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporinenephropathy. Kidney Int., 48, 431-438. https://doi.org/10.1038/ki.1995.311
  84. Zhong, Z., Arteel, G.E., Connor, H.D., Yin, M., Frankenberg, M.V., Stachlewitz, R.F., Raleigh, J.A., Mason, R.P. and Thurman, R.G. (1998). Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine. Am. J. Physiol., 275, F595-F604.

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  4. Preclinical evaluation of nephroprotective potential of a probiotic formulation LOBUN on Cyclosporine-A induced renal dysfunction in Wistar rats vol.53, pp.2, 2017, https://doi.org/10.1590/s2175-97902017000216041
  5. Bilateral ciliary body oedema under treatment with ciclosporine pp.1433-0423, 2017, https://doi.org/10.1007/s00347-017-0475-1
  6. Modulatory Role of Selenium and Vitamin E, Natural Antioxidants, against Bisphenol A-Induced Oxidative Stress in Wistar Albinos Rats vol.34, pp.3, 2018, https://doi.org/10.5487/TR.2018.34.3.231
  7. Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis vol.62, pp.3, 2018, https://doi.org/10.1007/s10384-018-0587-4