The Effect of Curcumin on Functional and Structural Alterations of the Liver in Rats after MDMA Consumption

Document Type: Original Article

Authors

1 Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

3 Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Background: Nowadays, one of the problems of human beings is drug addiction, which causes individual, economic and social damages. One of the most commonly used substances in parties is ecstasy pills or 3, 4-methylenedioxymethamphetamine (MDMA). This study seeks to assess the effect of curcumin in complications of ecstasy on liver tissue in rats.
Methods:48 male Wistar rats in six groups were treated with curcumin (20 µ mol/kg) and MDMA (20 mg/kg) simultaneously and non-simultaneously. At the end of the experiment, blood samples were collected, lipid profile, liver enzymes were measured and morphology of liver was done.
Results: MDMA consumption had adverse effect on lipid profile in comparison to the control group. Treatment of curcumin with MDMA consumption improved this effect of MDMA on lipid profile. Moreover, curcumin treatment concurrent with MDMA consumption increased liver enzymes, whereas consumption of MDMA for 15 days and curcumin treatment in the next 15 days decreased liver enzymes.
Conclusion: Our findings suggest that simultaneous consumption of MDMA and curcumin have a synergistic adverse effect on liver enzymes and liver tissue. It is assumed that MDMA intestinal absorption increased by curcumin. While non-simultaneous treatment of curcumin and MDMA improved undesirable effects of MDMA on liver that is assumed by antioxidant capabilities of curcumin.

Keywords


  1. Bernschneider-Reif S, Öxler F, Freudenmann R. The origin of MDMA (‘ecstasy’)–separating the facts from the myth. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2006;61(11):966-72.
  2. Ghodse AH, Kreek M-J. A rave at Ecstasy. Current Opinion in Psychiatry. 1997;10(3):191-3.
  3. Guneysel O, Onur OE, Akoglu H, Denizbasi A. Ecstasy-induced recurrent toxic hepatitis in a young adult. Current Therapeutic Research. 2008;69(3):260-5.
  4. Barrett SP, Darredeau C, Pihl RO. Patterns of simultaneous polysubstance use in drug using university students. Human Psychopharmacology: Clinical and Experimental. 2006;21(4):255-63.
  5. TUFAN ZK, Bulut C, Kinikli S, Irmak H, YILMAZ GR, Demİröz AP. A Case Report of Ecstasy-induced Acute Hepatic Failure. Turkish Journal of Medical Sciences. 2006;36(5):319-21.
  6. Mas M, Farré M, de la Torre R, Roset PN, Ortuño J, Segura J, et al. Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics. 1999;290(1):136-45.
  7. Wu D, Otton SV, Inaba T, Kalow W, Sellers EM. Interactions of amphetamine analogs with human liver CYP2D6. Biochemical pharmacology. 1997;53(11):1605-12.
  8. Carvalho M, Carvalho F, Remião F, de Lourdes Pereira M, Pires-das-Neves R, de Lourdes Bastos M. Effect of 3, 4-methylenedioxymethamphetamine (" ecstasy") on body temperature and liver antioxidant status in mice: influence of ambient temperature. Archives of toxicology. 2002;76(3):166-72.
  9. Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3, 4-methylenedioxymethamphetamine (MDMA,“ecstasy”). Pharmacological reviews. 2003;55(3):463-508.
  10. Maurer HH, Kraemer T, Springer D, Staack RF. Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis. Therapeutic drug monitoring. 2004;26(2):127-31.
  11. Pourahmad J, Eskandari MR, Nosrati M, Kobarfard F, Khajeamiri AR. Involvement of mitochondrial/lysosomal toxic cross-talk in ecstasy induced liver toxicity under hyperthermic condition. European journal of pharmacology. 2010;643(2):162-9.
  12. Andreu V, Mas A, Bruguera M, Salmerón JM, Moreno V, Nogué S, et al. Ecstasy: a common cause of severe acute hepatotoxicity. Journal of hepatology. 1998;29(3):394-7.
  13. Zhou H, S Beevers C, Huang S. The targets of curcumin. Current drug targets. 2011;12(3):332-47.
  14. Connor TJ, McNamara MG, Finn D, Currid A, O'Malley M, Redmond AM, et al. Acute 3, 4-methylenedioxymethamphetamine (MDMA) administration produces a rapid and sustained suppression of immune function in the rat. Immunopharmacology. 1998;38(3):253-60.
  15. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry. 1968;25:192-205.
  16. Khalaji N, Namyari M, Rasmi Y, Pourjabali M, Chodari L. Protective effect of curcumin on fertility of rats after exposure to compact fluorescent lamps: An experimental study. International Journal of Reproductive Biomedicine. 2018;16(7):447.
  17. Zaki NG, Abdel Kawy L. Chronic exposure to MDMA (ecstasy) induces DNA damage, impairs functional antioxidant cellular defenses, enhances the lipid peroxidation process and alters testes histopathology in male rat. The Egyptian Journal of Hospital Medicine. 2013;31(762):1-12.
  18. Zhou S-F, Liu J-P, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug metabolism reviews. 2009;41(2):89-295.
  19. Song B-J, Moon K-H, V Upreti V, D Eddington N, J Lee I. Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Current pharmaceutical biotechnology. 2010;11(5):434-43.
  20. Valente M, Araújo A, Silva R, Bastos M, Carvalho F, de Pinho PG, et al. Hepatic oxidative stress induced by methylone and MDPV: A comparison to MDMA. Toxicology Letters. 2015;2(238):S265.
  21. Halliwell B, Gutteridge JM. Free radicals in biology and medicine: Oxford University Press, USA; 2015.
  22. Neuman MG. First international symposium on the molecular pathology and clinical aspects of the inflamed liver: alcohol and cytokines. Clinical and Investigative Medicine. 1998;21(6):283.
  23. Surh YJ. Xenohormesis mechanisms underlying chemopreventive effects of some dietary phytochemicals. Annals of the New York Academy of Sciences. 2011;1229(1):1-6.
  24. Tesoriere L, Allegra M, Butera D, Gentile C, Livrea M. Cytoprotective effects of the antioxidant phytochemical indicaxanthin in β-thalassemia red blood cells. Free radical research. 2006;40(7):753-61.
  25. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alternative medicine review. 2009;14(2).
  26. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life sciences. 2006;78(18):2081-7.
  27. Xie Z, Wu B, Shen G, Li X, Wu Q. Curcumin alleviates liver oxidative stress in type 1 diabetic rats. Molecular medicine reports. 2018;17(1):103-8.
  28. Bao W, Li K, Rong S, Yao P, Hao L, Ying C, et al. Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction. Journal of ethnopharmacology. 2010;128(2):549-53.
  29. Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E. Ecstasy‐induced toxicity in rat liver. Liver International. 2000;20(1):8-15.
  30. Shahraki MR, Irani M. The effects of ecstasy on liver function tests, blood glucose, and lipids profile of male rats. International journal of high risk behaviors & addiction. 2014;3(4).
  31. Swerdlow NR, Koob GF, Cador M, Lorang M, Hauger R. Pituitary-adrenal axis responses to acute amphetamine in the rat. Pharmacology Biochemistry and Behavior. 1993;45(3):629-37.
  32. Sharma R, Gescher A, Steward W. Curcumin: the story so far. European journal of cancer. 2005;41(13):1955-68.