26Feb 2018

THE EFFECT OF TAURINE ON METHOTREXATE INDUCED HEPATORENAL TOXICITY IN RATS.

  • Physiology Department, Faculty of Medicine, Tanta University, Egypt.
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The aim of the work: Hepatorenal toxicity is a major side effect for methotrexate. Taurine is a natural compound with multiple pharmacological activities such as antioxidant, antiapoptotic and anti-inflammatory effects. This study investigated the effect of taurine on methotrexate-induced toxic effects in male albino rats. Methods: 40 male albino rats were divided into 4 groups (10 rats each): (control group): Rats injected with1ml saline intraperitoneally (i.p) for 6 days, (methotrexate treated group): Rats injected daily with 1ml saline i.p for 5 days, at the 6th day they were injected i.p with a single dose of methotrexate (20 mg/kg), (taurine treated group): Rats injected with taurine 100 mg/kg daily i.p for 6 days, (taurine+methotrexate treated group): Rats injected i.p with taurine 100 mg/kg daily for 5 days at the 6th day after the last dose of taurine, rats were injected i.p with a single dose of methotrexate (20 mg/kg). Results: Methotrexate administration resulted in hepatorenal toxicity, oxidative stress, lipid peroxidation and apoptosis. These results were confirmed by histopathology and by detection of DNA fragmentation by gel electrophoresis. Taurine administration before methotrexate improved hepatorenal functions caused a reduc?tion in oxidative stress, lipid peroxidation, and elevation in the activity of antioxidant enzymes. This was confirmed by the histopathological findings of hepatic and renal tissue and by the reduction in DNA fragmentation. Conclusion: Taurine supplemen?tation had beneficial effects on liver and kidney functions, with marked reductions in oxidative stress and apoptosis induced by methotrexate.


1. Abo-Haded, H.M., Elkablawy, M.A., Al-Johani, Z., Al-ahmadi, O. & El-Agamy, D.S. (2017). Hepatoprotective effect of sitagliptin against methotrexate-induced liver toxicity. PloS one, 12(3), e0174295. 2. Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121-126. 3. Ahmad, M.K., Khan, A.A., Ali, S.N. & Mahmood, R. (2015). Chemoprotective effect of taurine on potassium bromate-induced DNA damage, DNA-protein cross-linking and oxidative stress in rat intestine. PloS one, 10(3), e0119137. 4. Ahmed, W., Zaki, A. & Nabil, T. (2015). Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic aqueous extract in rat. Turkish journal of medical sciences, 45(3), 507-516. 5. Aithal, G.P. (2011). Hepatotoxicity related to antirheumatic drugs. Nature Reviews Rheumatology, 7(3), 139-150. 6. Al-Asmari, A.K., Al-Zahrani, A.M., Khan, A.Q., Al-Shahrani, H.M. & Ali Al Amri, M. (2016). Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study. Human & experimental toxicology, 35(1), 10-20. 7. Bartels, H., B?hmer, M.& Heierli, C. (1972). Serum creatinine determination without protein precipitation. Clinicachimicaacta; international journal of clinical chemistry, 37, 193-197. 8. Bath, R.K., Brar, N.K., Forouhar, F.A. & Wu, G.Y. (2014). A review of methotrexate‐associated hepatotoxicity. Journal of digestive diseases, 15(10), 517-524. 9. Beutler, E. (1963). Improved method for determination of blood glutathione. J Lab Clin Med, 61(5), 882-888. 10. Braun J & Rau R. An update on methotrexate. CurrOpinRheumatol 2009; 21: 216?22 11. ?akır, T., ?zkan, E., Dulundu, E., Topaloğlu, ?., Şehirli, A. ?., Ercan, F., Şener E.& Şener, G. (2011). Caffeic acid phenethyl ester (CAPE) prevents methotrexate‐induced hepatorenal oxidative injury in rats. Journal of Pharmacy and Pharmacology, 63(12), 1566-1571. 12. Czarnecka-Operacz, M., & Sadowska-Przytocka, A. (2014). The possibilities and principles of methotrexate treatment of psoriasis?the updated knowledge. Advances in Dermatology and Allergology/PostȩpyDermatologii Alergologii, 31(6), 392. 13. David, A.V.A., Satyanarayana, N., Parasuraman, S., Bharathi, S. & Arulmoli, R. (2016). Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study. Indian Journal of Pharmaceutical Education and Research, 50(3), S200-S208. 14. Deacon, A. (2009). Calculations in laboratory science. ACB Venture Publications. 15. Demircioğlu, R.İ., Usta, B., Sert, H., Muslu, B., & G?zdemir, M. (2011). Taurine is protective against oxidative stress during cold ischemia in the rat kidney. Turkish Journal of Medical Sciences, 41(5), 843-849. 16. Depboylu, B., Doğru‐Abbasoğlu, S., Erbil, Y., Olga?, V., Alış, H., Ayka?‐Toker, G., & Uysal, M. (2008). Effect of taurine on oxidative stress and apoptosis‐related protein expression in trinitrobenzenesulphonic acid‐induced colitis. Clinical & Experimental Immunology, 152(1), 102-110. 17. Devi LE., Laishram V., Meetei UD., & Jamoh A. (2016). Effect of taurine on renal pathophysiology in experimental animals. Int J Pharm Bio Sci, 7(4), 179 ? 183. 18. Devi, S.L. & Anuradha, C.V. (2010). Mitochondrial damage, cytotoxicity and apoptosis in iron-potentiated alcoholic liver fibrosis: amelioration by taurine. Amino Acids, 38(3), 869-879. 19. El Kader, M.A.A., El Kafrawy, M.H., Tolba, A.M., Ali, M.M., & Mohamed, A.S. (2015). Evaluation of taurine role on some biochemical and histological alterations in γ-irradiated rats. International Journal of Pharmaceutical Sciences Review and Research, 30(1), 263-271. 20. El-Sayed, W. M., Al-Kahtani, M. A., & Abdel-Moneim, A. M. (2011). Prophylactic and therapeutic effects of taurine against aluminum-induced acute hepatotoxicity in mice. Journal of hazardous materials, 192(2), 880-886. 21. El-Sheikh AA., Morsy MA., Abdalla AM., Hamouda AH. & Alhaider IA. (2015). Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators of inflammation, 2015 (859383), 1-12. 22. Hemeida, A.R & Omar, M.M. (2008). Curcumin Attenuates Methotrexate-Induced Hepatic Oxidative Damage in Rats. Journal of the Egyptian Nat Cancer Inst, 20(2), 141-148. 23. Huxtable, R. J. (1992). Physiological actions of taurine. Physiological reviews, 72(1), 101-163. 24. Issabeagloo E., Taghizadiyeh M. & Kermanizadeh P. (2011). Hepatoprotective effect of taurine against oxidative stress due to methotrexate in rat. American Journal of Animal and Veterinary Sciences, 6(4), 187-192. 25. Jahovic, N., ?evik, H., Şehirli, A.?., Yeğen, B.?. & Şener, G. (2003). Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats. Journal of Pineal Research, 34(4), 282-287. 26. Jong, C. J., Azuma, J., & Schaffer, S. (2012). Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino acids, 42(6), 2223-2232. 27. Kasibhatla, S., Amarante-Mendes, G.P., Finucane, D., Brunner, T., Bossy-Wetzel, E. & Green, D.R. (2006). Analysis of DNA fragmentation using agarose gel electrophoresis. Cold Spring Harbor Protocols, 2006(1), pdb-prot4429. 28. Kim, C. & Cha, Y.N. (2014). Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects. Amino Acids, 46(1), 89-100. 29. Kim, W., Kim, H.U., Lee, H.N., Kim, S.H., Kim, C., Cha, Y.N., Joe Y., Chung HT., Jang J., Kim K. & Suh Y.G.(2015). Taurine chloramine stimulates efferocytosis through upregulation of Nrf2-mediated heme oxygenase-1 expression in murine macrophages: possible involvement of carbon monoxide. Antioxidants &Redox Signaling, 23(2), 163-177. 30. Leit?o, Renata FC, Gerly AC Brito, Reinaldo B. Ori?, Manuel B. Braga-Neto, Emmanuelle AL Bellaguarda, Johann V. Silva, Antoniella S. Gomes AS., Lima-J?nior RC., Siqueira FJ., Freire RS., Vale ML. & Ribeiro RA. "Role of inducible nitric oxide synthase pathway on methotrexate-induced intestinal mucositis in rodents." BMC Gastroenterology 11, no. 1 (2011): 90. 31. Marcinkiewicz, J.& Kontny, E. (2014). Taurine and inflammatory diseases. Amino Acids, 46(1), 7-20. 32. Maskos, K., Fernandez-Catalan, C., Huber, R., Bourenkov, G.P., Bartunik, H., Ellestad, G.A. & Davis, R. (1998). Crystal structure of the catalytic domain of human tumor necrosis factor-α-converting enzyme. Proceedings of the National Academy of Sciences, 95(7), 3408-3412. 33. McLeay, Y., Stannard, S., Houltham, S. & Starck, C. (2017). Dietary thiols in exercise: oxidative stress defense, exercise performance, and adaptation. Journal of the International Society of Sports Nutrition, 14(1), 12. 34. Mehrzadi, Saeed, ImanFatemi, Mahdi Esmaeilizadeh, HabibGhaznavi, HadiKalantar, & Mehdi Goudarzi. "Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats." Biomedicine & Pharmacotherapy, 97(2018), 233-239. 35. Montgomery, H.A. & Dymock, J.F. (1961). Nitrite assay in tissue fluids. Analyst, 86, 414. 36. Nagai, K., Fukuno, S., Oda, A. & Konishi, H. (2016). Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses. Anti-cancer drugs, 27(1), 17-23. 37. Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry, 95(2), 351-358 38. Pandit, A., Sachdeva, T., & Bafna, P. (2012). Drug-induced hepatotoxicity: A review. Journal of Applied Pharmaceutical Science, 02 (05),233-243. 39. Porter, A. G.& J?nicke, R. U. (1999). Emerging roles of caspase-3 in apoptosis. Cell Death &Differentiation, 6(2). 40. Reitman, S., & Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28(1), 56-63. 41. Sakeran, M. I., Zidan, N., Rehman, H., Aziz, A. T., & Saggu, S. (2014). Abrogation by Trifoliumalexandrinum root extract on hepatotoxicity induced by acetaminophen in rats. Redox Report, 19(1), 26-33. 42. Samson F., Colip F. & Patterson J. (1957). Procedure for the Use of Sodium Pentobarbital (Nembutal?) Anesthesia in Classroom Experiments with Rats. Transactions of the Kansas Academy of Science, (1903), 425-428. 43. Tiffany, T.O., Jansen, J.M., Burtis, C.A., Overton, J.B., & Scott, C.D. (1972). Enzymatic kinetic rate and end-point analyses of substrate, by use of a GeMSAEC fast analyzer. Clinical Chemistry, 18(8), 829-840. 44. Ulusoy, H.B., ?zt?rk, İ. & S?nmez, M.F. (2016). Protective effect of propolis on methotrexate-induced kidney injury in the rat. Renal Failure, 38(5), 744-750. 45. Zhang, Z., Liu, D., Yi, B., Liao, Z., Tang, L., Yin, D., & He, M. (2014). Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model. Molecular Medicine Reports, 10(5), 2255-2262.

[Marwa Mahmoud Awad, Sahar Ahmed Elsawy, Ahmed ALsayed Abdalfattah and Salma Elwy Nassar. (2018); THE EFFECT OF TAURINE ON METHOTREXATE INDUCED HEPATORENAL TOXICITY IN RATS. Int. J. of Adv. Res. 6 (Feb). 1778-1791] (ISSN 2320-5407). www.journalijar.com


marwa mahmoud awad saleh
physiology

DOI:


Article DOI: 10.21474/IJAR01/6618      
DOI URL: https://dx.doi.org/10.21474/IJAR01/6618