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Early abstinence of crack-cocaine is effective to attenuate oxidative stress and to improve antioxidant defences

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Abstract

Rationale

Preclinical studies have shown that cocaine exposure and withdrawal are associated with cellular oxidative stress damage. However, the impact of crack-cocaine dependence on oxidative stress biomarkers remains unclear. Here, we assessed peripheral oxidative stress and antioxidant defences during two periods of crack-cocaine detoxification treatment and associated these changes with psychological morbidity.

Methods

Thirty female inpatients were recruited, and plasma samples were collected at the 4th and 18th days of abstinence; 30 healthy controls were also recruited. Plasma levels of protein carbonyl, protein thiol content, superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced reduced (GSH) and total reactive antioxidant potential (TRAP) were measured by standard methods; the questionnaires Cocaine Selective Severity Assessment, Beck Depressive Inventory and the Addiction Severity Index were applied.

Results

We report higher oxidative stress damage after 4 days of detoxification, as shown by increased total thiol content and protein carbonylation when compared with control group and after 18 days of detoxification. After 18 days of treatment, we observed a recovery of the oxidative stress damage and increase of the antioxidant defences, as shown by higher levels of SOD, GPx, GSH and TRAP. There was a positive correlation between protein carbonylation and psychological variables; in contrast, there was a negative correlation between TRAP levels and clinical assessments.

Conclusions

Taken together, these results suggest that drug rehabilitation treatment was effective in decreasing oxidative damage represented by the reduction in biological markers, which are closely related to the severity of withdrawal symptoms.

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References

  • Abdalla RR, Madruga CS, Ribeiro M, Pinsky I, Caetano R, Laranjeira R (2014) Prevalence of cocaine use in Brazil: data from the II Brazilian National Alcohol and Drugs Survey (BNADS). Addict Behav 39:297–301

    Article  PubMed  Google Scholar 

  • Becker JB, Hu M (2008) Sex differences in drug abuse. Front Neuroendocrinol 29:36–47

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Becker JB, Perry AN, Westenbroek C (2012) Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis. Biol Sex Differ 3:14

    Article  PubMed Central  PubMed  Google Scholar 

  • Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272:20313–20316

    Article  CAS  PubMed  Google Scholar 

  • Biswas S, Chida AS, Rahman I (2006) Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol 71:551–564

    Article  CAS  PubMed  Google Scholar 

  • Bough KJ, Amur S, Lao G, Hemby SE, Tannu NS, Kampman KM, Schmitz JM, Martinez D, Merchant KM, Green C, Sharma J, Dougherty AH, Moeller FG (2014) Biomarkers for the development of new medications for cocaine dependence. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol 39:202–219

    Article  CAS  Google Scholar 

  • Dietrich JB, Mangeol A, Revel MO, Burgun C, Aunis D, Zwiller J (2005) Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures. Neuropharmacol 48:965–974

    Article  CAS  Google Scholar 

  • Dresch MT, Rossato SB, Kappel VD, Biegelmeyer R, Hoff ML, Mayorga P, Zuanazzi JA, Henriques AT, Moreira JC (2009) Optimization and validation of an alternative method to evaluate total reactive antioxidant potential. Anal Biochem 385:107–114

    Article  CAS  PubMed  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • Gutteridge JM, Halliwell B (2000) Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci 899:136–147

    Article  CAS  PubMed  Google Scholar 

  • Gutteridge JM, Halliwell B (2010) Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun 393:561–564

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B (1996) Antioxidants in human health and disease. Annu Rev Nutr 16:33–50

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658

    Article  CAS  PubMed  Google Scholar 

  • Hastings TG (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64:919–924

    Article  CAS  PubMed  Google Scholar 

  • Hermida-Ameijeiras A, Mendez-Alvarez E, Sanchez-Iglesias S, Sanmartin-Suarez C, Soto-Otero R (2004) Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions. Neurochem Int 45:103–116

    Article  CAS  PubMed  Google Scholar 

  • Hser YI, Hoffman V, Grella CE, Anglin MD (2001) A 33-year follow-up of narcotics addicts. Arch Gen Psychiatr 58:503–508

    Article  CAS  PubMed  Google Scholar 

  • Huang MC, Chen CH, Peng FC, Tang SH, Chen CC (2009) Alterations in oxidative stress status during early alcohol withdrawal in alcoholic patients. J Formos Med Assoc =Taiwan yi zhi 108:560–569

    Article  Google Scholar 

  • Kampman KM, Pettinati HM, Volpicelli JR, Oslin DM, Lipkin C, Sparkman T, O’Brien CP (2004) Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol. Am J Addict / Am Acad Psychiatrists Alcohol Addict 13:74–82

    Google Scholar 

  • Klatt P, Lamas S (2000) Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem / FEBS 267:4928–4944

    Article  CAS  Google Scholar 

  • Kovacic P (2005) Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer. Med Hypotheses 64:350–356

    Article  CAS  PubMed  Google Scholar 

  • Kovacic P, Cooksy A (2005) Iminium metabolite mechanism for nicotine toxicity and addiction: oxidative stress and electron transfer. Med Hypotheses 64:104–111

    Article  CAS  PubMed  Google Scholar 

  • Leichert LI, Jakob U (2004) Protein thiol modifications visualized in vivo. PLoS Biol 2:e333

    Article  PubMed Central  PubMed  Google Scholar 

  • Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    Article  CAS  PubMed  Google Scholar 

  • Lipton JW, Gyawali S, Borys ED, Koprich JB, Ptaszny M, McGuire SO (2003) Prenatal cocaine administration increases glutathione and alpha-tocopherol oxidation in fetal rat brain. Brain Res Dev Brain Res 147:77–84

    Article  CAS  PubMed  Google Scholar 

  • Lissi E, Salim-Hanna M, Pascual C, del Castillo MD (1995) Evaluation of total antioxidant potential (TRAP) and total antioxidant reactivity from luminol-enhanced chemiluminescence measurements. Free Radic Biol Med 18:153–158

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • McLellan AT, Luborsky L, Woody GE, O’Brien CP (1980) An improved diagnostic evaluation instrument for substance abuse patients. The addiction severity index. J Nerv Ment Dis 168:26–33

    Article  CAS  PubMed  Google Scholar 

  • Meleca RJ, Burgio DL, Carr RM, Lolachi CM (1997) Mucosal injuries of the upper aerodigestive tract after smoking crack or freebase cocaine. Laryngoscope 107:620–625

    Article  CAS  PubMed  Google Scholar 

  • Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248

    Article  CAS  PubMed  Google Scholar 

  • Moselhy HF, Reid RG, Yousef S, Boyle SP (2013) A specific, accurate, and sensitive measure of total plasma malondialdehyde by HPLC. J Lipid Res 54:852–858

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Muriach M, Lopez-Pedrajas R, Barcia JM, Sanchez-Villarejo MV, Almansa I, Romero FJ (2010) Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate. J Neurochem 114:675–684

    Article  CAS  PubMed  Google Scholar 

  • Nadeem A, Siddiqui N, Alharbi NO, Alharbi MM, Imam F, Sayed-Ahmed MM (2014) Glutathione modulation during sensitization as well as challenge phase regulates airway reactivity and inflammation in mouse model of allergic asthma. Biochimie

  • Narvaez JC, Magalhaes PV, Fries GR, Colpo GD, Czepielewski LS, Vianna P, Chies JA, Rosa AR, Von Diemen L, Vieta E, Pechansky F, Kapczinski F (2013) Peripheral toxicity in crack cocaine use disorders. Neurosci Lett 544:80–84

    Article  CAS  PubMed  Google Scholar 

  • Ndikum-Moffor FM, Schoeb TR, Roberts SM (1998) Liver toxicity from norcocaine nitroxide, an N-oxidative metabolite of cocaine. J Pharmacol Exp Ther 284:413–419

    CAS  PubMed  Google Scholar 

  • Numa R, Kohen R, Poltyrev T, Yaka R (2008) Tempol diminishes cocaine-induced oxidative damage and attenuates the development and expression of behavioral sensitization. Neurosci 155:649–658

    Article  CAS  Google Scholar 

  • Pacifici R, Fiaschi AI, Micheli L, Centini F, Giorgi G, Zuccaro P, Pichini S, Di Carlo S, Bacosi A, Cerretani D (2003) Immunosuppression and oxidative stress induced by acute and chronic exposure to cocaine in rat. Int Immunopharmacol 3:581–592

    Article  CAS  PubMed  Google Scholar 

  • Pomierny-Chamiolo L, Moniczewski A, Wydra K, Suder A, Filip M (2013) Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine. Neurotox Res 23:92–102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rahman I, Biswas SK, Jimenez LA, Torres M, Forman HJ (2005) Glutathione, stress responses, and redox signaling in lung inflammation. Antioxid Redox Signal 7:42–59

    Article  CAS  PubMed  Google Scholar 

  • Sandro G, Arijit N, David V (2004) The social epidemiology of substance use. Epidemiol Rev 26:36–52

    Article  Google Scholar 

  • Sordi AO, Pechansky F, Kessler FH, Kapczinski F, Pfaffenseller B, Gubert C, de Aguiar BW, de Magalhaes Narvaez JC, Ornell F, von Diemen L (2014) Oxidative stress and BDNF as possible markers for the severity of crack cocaine use in early withdrawal. Psychopharmacol. doi:10.1007/s00213-014-3542-1

    Google Scholar 

  • Usdan SL, Schumacher JE, Milby JB, Wallace D, McNamara C, Michael M (2001) Crack cocaine, alcohol, and other drug use patterns among homeless persons with other mental disorders. Am J Drug Alcohol Abuse 27:107–120

    Article  CAS  PubMed  Google Scholar 

  • Vargas HO, Nunes SO, de Castro MR, Vargas MM, Barbosa DS, Bortolasci CC, Venugopal K, Dodd S, Berk M (2013) Oxidative stress and inflammatory markers are associated with depression and nicotine dependence. Neurosci Lett 544:136–140

    Article  CAS  PubMed  Google Scholar 

  • Viola TW, Tractenberg SG, Levandowski ML, Pezzi JC, Bauer ME, Teixeira AL, Grassi-Oliveira R (2014) Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress. J Psychiatr Neurosci: JPN 39:206–214

    Article  Google Scholar 

  • Wang L, Muxin G, Nishida H, Shirakawa C, Sato S, Konishi T (2007) Psychological stress-induced oxidative stress as a model of sub-healthy condition and the effect of TCM. Evidence-based complementary and alternative medicine. eCAM 4:195–202

    PubMed Central  PubMed  Google Scholar 

  • Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333

    Article  CAS  PubMed  Google Scholar 

  • Wheatley RA (2010) Some recent trends in the analytical chemistry of lipid peroxidation. TrAC Trends Anal Chem 19:617–628

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from CNPq and FAPERGS (MEB and RG-O) and CAPES. The funding institutions had no further roles in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflicts of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

    Aline Zaparte, Rodrigo Grassi-Oliveira & Moisés E. Bauer

  2. Postgraduate Program in Pediatrics and Children’s Health, PUCRS, Porto Alegre, RS, Brazil

    Thiago W. Viola

  3. Cognitive Neuroscience Research Group (GNCD), Centre of Studies and Research in Traumatic Stress (NEPTE), Postgraduate Program in Psychology, PUCRS, Porto Alegre, RS, Brazil

    Rodrigo Grassi-Oliveira

  4. Centro de Estudos em Estresse Oxidativo, Programa de Pós Graduação em Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Maurilio da Silva Morrone & José C. Moreira

  5. Institute of Biomedical Research and Faculty of Biosciences, Hospital São Lucas–PUCRS, Av. Ipiranga 6690, 2 andar, PO Box 1429, Porto Alegre, RS, 90610-000, Brazil

    Moisés E. Bauer

Authors
  1. Aline Zaparte
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  2. Thiago W. Viola
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  4. Maurilio da Silva Morrone
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  5. José C. Moreira
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  6. Moisés E. Bauer
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Corresponding author

Correspondence to Moisés E. Bauer.

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Zaparte, A., Viola, T.W., Grassi-Oliveira, R. et al. Early abstinence of crack-cocaine is effective to attenuate oxidative stress and to improve antioxidant defences. Psychopharmacology 232, 1405–1413 (2015). https://doi.org/10.1007/s00213-014-3779-8

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  • DOI: https://doi.org/10.1007/s00213-014-3779-8

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