Oxidative stress in rat kidneys due to 3,4-methylenedioxymetamphetamine (ecstasy) toxicity
Corresponding Author
MILICA NINKOVIĆ
Institute of Medical Research, Military Medical Academy,
Dr Milica Ninković, Institute of Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Republic of Serbia. Email: [email protected]Search for more papers by this authorVESNA SELAKOVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorMIRJANA ÐUKIĆ
Department of Toxicology, Faculty of Pharmacy, Belgrade, Republic of Serbia
Search for more papers by this authorPETAR MILOSAVLJEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorIVANA VASILJEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorMARINA JOVANOVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorŽIVORAD MALIČEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorCorresponding Author
MILICA NINKOVIĆ
Institute of Medical Research, Military Medical Academy,
Dr Milica Ninković, Institute of Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Republic of Serbia. Email: [email protected]Search for more papers by this authorVESNA SELAKOVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorMIRJANA ÐUKIĆ
Department of Toxicology, Faculty of Pharmacy, Belgrade, Republic of Serbia
Search for more papers by this authorPETAR MILOSAVLJEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorIVANA VASILJEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorMARINA JOVANOVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorŽIVORAD MALIČEVIĆ
Institute of Medical Research, Military Medical Academy,
Search for more papers by this authorSUMMARY:
Aim: The mechanism of MDMA (3,4-methylenedioxymethamphetamine)-induced toxicity is believed to be, in part, due to enhanced oxidative stress. As MDMA is eliminated via the kidney, the aim of this study was to investigate whether MDMA created conditions of oxidative stress within rat kidney.
Methods: Adult male Wistar rats were divided into three groups, control treatment (water), acute MDMA administration (single oral dose: 5, 10, 20 or 40 mg/kg body weight) and subacute MDMA administration (5, 10, or 20 mg/kg body weight per day during 14 days). Animals were sacrificed 8 h after the single oral MDMA administration in the acute MDMA administration group and after the last MDMA administration in the subacute MDMA administration group. Rectal temperature measurements, oxidative stress status parameters and histological examinations were performed.
Results: In all MDMA-administered rats, rectal temperature markedly increased peaking approximately 1 h after MDMA ingestion. Superoxide dismutase activity and thiobarbituric acid reactive substances increased after MDMA administration. Histological examinations of the kidney revealed dose-dependent disruption of tissue structure in subacute MDMA-administered rats. The latter was not observed in acute MDMA-administered rats.
REFERENCES
- 1 Kalant H. The pharmacology and toxicology of ‘extasy’ (MDMA) and related drugs. CMAJ 2001; 165: 917–28.
- 2 Malpass A, White JM, Irvine RJ, Somogyi AA, Bochner F. Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and dark Agoutin rats. Pharmacol. Toxicol. 1999; 64: 29–34.
- 3 Gowing LR, Henry-Edwards SM, Irwine RJ, Ali RL. The health effects of ecstasy: a literature review. Drug Alcohol Rev. 2002; 21: 53–63.
- 4 Gurtman CG, Morley KC, Li KM, Hunt GE, McGregor IS. Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion. Eur. J. Pharmacol. 2002; 446: 89–96.
- 5 Slikker W, Holson RR, Ali SF et al. Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate. Neurotoxicology 1989; 10: 529–42.
- 6 Irvine RJ, Toop NP, Phillis BD, Lewanowitsch T. The acute cardiovascular effects of 3,4 methlenedioxymetamphetamine (MDMA) and p-metoxyamphetamine (PMA). Addict. Biol. 2001; 6: 45–54.
- 7 De la Torre R, Farre M, Ortuno J et al. Non-linear pharmacokinetics of MDMA (ecstasy) in humans. Br. J. Clin. Pharmacol. 2000; 49: 104–9.
- 8 Lyles J, Cadet JL. Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain. Res. Rev. 2003; 42: 155–68.
- 9 Fleckenstein A, Wilkins DG, Gibb JW, Hanson GR. Interaction between hyperthermia and oxigen radical formation in the 5-hydroxytryptaminergic response to a single methamphetamine administration. J. Pharmacol. Exp. Ther. 1997; 283: 281–5.
- 10 Carvalho M, Carvalho F, Remiao F et al. Effect of 3,4-methylenedioxymethamphetamine ecstasy on body temperature and liver antioxidant status in mice: influence of ambient temperature. Arch. Toxicol. 2002; 76: 166–72.
- 11 Fahal IB, Sallomi DF, Yaqoob M, Bell GM. Acute renal failure after extasy. BMJ 1992; 305: 29.
- 12 Kunsdorf-Wnuk A, Musiol E, Karpel E, Arct-Danielak D. Rhabdomyolysis, disseminated intravascular coagulation and acute renal failure after severe narcotics intoxication (MDMA, THC, amphetamine). Pol. Merkur. Lekarski 2005; 18: 436–9.
- 13 Ninković M, Maličević Ž, Selaković V, Simić I, Vasiljević I. N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: oxidative stress after acute and chronic administration. Vojnosanit. Pregl. 2004; 61: 125–31.
- 14 Uputstvo za dobru laboratorijsku praksu. Sluzbeni List SRJ 2001; 40: 1–15.
- 15 McFadden K, Gillespie J, Carney B, O'driscoll D. Development and application of a high-perfomance liquid chromatography method using monolithic. Brain. Res. Rev. 2003; 42: 155–68.
- 16 Lyles J, Cadet JL. Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain Res. Rew. 2003; 42: 155–68.
- 17 Gurd JW, Jones LR, Mahler HR, Moore WJ. Isolation, and partial characterization of rat brain synaptic plasma membranes. J. Neurochem. 1974; 22: 281–90.
- 18 Lowry OH, Passonneau JV (eds). A Flexible System of Enzymatic Analysis, 2nd edn. New York: Academic Press, 1974.
- 19 Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autooxidation. Anal. Biochem. 1978; 90: 81–9.
- 20 Mizuno Y, Ohta K. Regional distributions of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of oxygen free radicals, and some of the related enzymes in adult and aged rat brains. J. Neurochem. 1986; 46: 1344–52.
- 21 Kwon C, Zaritsky A, Dharnidharka VR. Transient proximal tubular renal injury following ecstasy ingestion. Pediatr. Nephrol. 2003; 18: 820–2.
- 22 Kreth KP, Kovar KA, Schwab M, Zanger UM. Identification of the human cytochromes P450 involved in the oxidative metabolism of ‘extasy’-related designer drugs. Biochem. Pharmacol. 2000; 59: 1563–71.
- 23 Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. Role of quinones in toxicology. Chem. Res. Toxicol. 2001; 3: 135–60.
- 24 Carvalho M, Hawksworth G, Milhazes N et al. Role of metabolites in MDMA (extasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells. Arch. Toxicol. 2002; 76: 581–8.
- 25 Bredt DS, Snyder SH. Nitric oxide: a physiological messenger molecule. Annu. Rev. Biochem. 1994; 63: 175–95.
- 26 Taraska T, Finnegan KT. Nitric oxide and the neurotoxic effects of methamphetamine and 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 1997; 280: 941–7.
- 27 Aulak KS, Miyagi M, Yan L et al. Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. PNAS 2001; 98: 12056–61.
- 28 Ishigami A, Tokunada I, Gotohda T, Kubo S. Immunohistochemical study of myoglobin and oxidative injury/related markers in the kidney of methamphetamine abusers. Leg. Med. (Tokyo) 2003; 5: 42–8.
- 29 Holt SG, Moore KP. Pathogenesis and treatment of renal dysfunction in rhabdomyolisis. Intensive Care Med. 2001; 27: 803–11.
- 30 Malberg JE, Seiden LS. Small changes in ambient temperature cause large changes in 3,4-(MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J. Neurosci. 1998; 18: 5086–94.
- 31 Sprague JE, Banks ML, Cook VJ, Mills EM. Hypothalamic-pituitary-thyroid axis and sympathetic nervous system involvement in hyperthermia induced by 3,4-methylenedioxymethamphetamine (Ecstasy). J. Pharmacol. Exp. Ther. 2003; 305: 159–66.
- 32 Maldonado E, Navarro JF. MDMA (‘extasy’) exhibits an anxiogenic-like activity in social encounters between male mice. Pharm. Res. 2001; 44: 1096–186.
- 33 Cole JC, Sumnall HR. Altered states: the clinical effects of ecstasy. Pharmacol. Ther. 2003; 98: 35–58.
- 34 Shankaran M, Yamamoto BK, Gudelsky GA. Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum. J. Neurochem. 1999; 72: 2516–22.
- 35 Darvesh AS, Shankaran M, Gudelsky GA. Methylenedioxymethamphetamine produces glycogenolisis and increases the extracellular concentration of glucose in the rat brain. J. Pharmacol. Exp. Ther. 2002; 301: 138–44.
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