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2000
Volume 22, Issue 2
  • ISSN: 1871-5257
  • E-ISSN: 1875-6182

Abstract

Aims

This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients.

Objectives

This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation.

Methods

BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation.

Results

The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP.

Conclusion

In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

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References

  1. MégarbaneB. HreicheR. PirnayS. MarieN. BaudF.J. Does high-dose buprenorphine cause respiratory depression?: Possible mechanisms and therapeutic consequences.Toxicol. Rev.2006252798510.2165/00139709‑200625020‑0000216958555
    [Google Scholar]
  2. JanssonL.M. SpencerN. McConnellK. VelezM. TutenM. HarrowC.A. JonesH.E. SwortwoodM.J. BarnesA.J. ScheidweilerK.B. HuestisM.A. Maternal buprenorphine maintenance and lactation.J. Hum. Lact.201632467568110.1177/089033441666319827563013
    [Google Scholar]
  3. KongstorpM. BogenI.L. StirisT. AndersenJ.M. High accumulation of methadone compared with buprenorphine in fetal rat brain after maternal exposure.J. Pharmacol. Exp. Ther.2019371113013710.1124/jpet.119.25953131358559
    [Google Scholar]
  4. ChayP.C.W. DuffyB.J. WalkerJ.S. Pharmacokinetic-pharmacodynamic relationships of morphine in neonates.Clin. Pharmacol. Ther.199251333434210.1038/clpt.1992.301544290
    [Google Scholar]
  5. FeilbergV.L. RosenborgD. ChristensenC.B. MogensenJ.V. Excretion of morphine in human breast milk.Acta Anaesthesiol. Scand.198933542642810.1111/j.1399‑6576.1989.tb02938.x2800981
    [Google Scholar]
  6. IlettK.F. HackettL.P. GowerS. DohertyD.A. HamiltonD. BartuA.E. Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment.Breastfeed. Med.20127426927410.1089/bfm.2011.009622011128
    [Google Scholar]
  7. LindemalmS. NydertP. SvenssonJ.O. StahleL. SarmanI. Transfer of buprenorphine into breast milk and calculation of infant drug dose.J. Hum. Lact.200925219920510.1177/089033440832829519136395
    [Google Scholar]
  8. MittalL. Buprenorphine for the treatment of opioid dependence in pregnancy.J. Perinat. Neonatal Nurs.201428317818410.1097/JPN.000000000000004425062519
    [Google Scholar]
  9. BrownS.M. HoltzmanM. KimT. KharaschE.D. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active.Anesthesiology201111561251126010.1097/ALN.0b013e318238fea022037640
    [Google Scholar]
  10. WilesJ.R. IsemannB. WardL.P. VinksA.A. AkinbiH. Current management of neonatal abstinence syndrome secondary to intrauterine opioid exposure.J. Pediatr.2014165344044610.1016/j.jpeds.2014.05.01024948346
    [Google Scholar]
  11. BruceR.D. AlticeF.L. MoodyD.E. MorseG.D. AndrewsL. LinS-N. , S-N Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir.J. Acquir. Immune Defic. Syndr.2010545511514
    [Google Scholar]
  12. EtaeeF. AsadbegiM. TaslimiZ. ShahidiS. SarihiA. Soleimani AslS. KomakiA. The effects of methamphetamine and buprenorphine, and their interaction on anxiety-like behavior and locomotion in male rats.Neurosci. Lett.201765517217810.1016/j.neulet.2017.04.04328698151
    [Google Scholar]
  13. UchiyamaM. MiharaM. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test.Anal. Biochem.197886127127810.1016/0003‑2697(78)90342‑1655387
    [Google Scholar]
  14. SunJ. ZhangX. BroderickM. FeinH. Measurement of nitric oxide production in biological systems by using Griess reaction assay.Sensors20033827628410.3390/s30800276
    [Google Scholar]
  15. RothE.F.Jr GilbertH.S. The pyrogallol assay for superoxide dismutase: Absence of a glutathione artifact.Anal. Biochem.19841371505310.1016/0003‑2697(84)90344‑06731808
    [Google Scholar]
  16. FischerG. JohnsonR.E. EderH. JagschR. PeternellA. WeningerM. LangerM. AschauerH.N. Treatment of opioid-dependent pregnant women with buprenorphine.Addiction200095223924410.1046/j.1360‑0443.2000.95223910.x10723852
    [Google Scholar]
  17. KahilaH. SaistoT. Kivitie-KallioS. HaukkamaaM. HalmesmäkiE. A prospective study on buprenorphine use during pregnancy: Effects on maternal and neonatal outcome.Acta Obstet. Gynecol. Scand.200786218519010.1080/0001634060111077017364281
    [Google Scholar]
  18. PrithamU.A. TroeseM. StetsonA. Methadone and buprenorphine treatment during pregnancy: What are the effects on infants?Nurs. Womens. Health200711655856710.1111/j.1751‑486X.2007.00243.x18088293
    [Google Scholar]
  19. MarquetP. ChevrelJ. LavignasseP. MerleL. LachâtreG. Buprenorphine withdrawal syndrome in a newborn.Clin. Pharmacol. Ther.199762556957110.1016/S0009‑9236(97)90053‑99390114
    [Google Scholar]
  20. JohnsonR.E. JonesH.E. JasinskiD.R. SvikisD.S. HaugN.A. JanssonL.M. KissinW.B. AlpanG. LantzM.E. ConeE.J. WilkinsD.G. GoldenA.S. HugginsG.R. LesterB.M. Buprenorphine treatment of pregnant opioid-dependent women: Maternal and neonatal outcomes.Drug Alcohol Depend.20016319710310.1016/S0376‑8716(00)00194‑011297835
    [Google Scholar]
  21. SchindlerS.D. EderH. OrtnerR. RohrmeisterK. LangerM. FischerG. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy.Wiley Online Library200310.1046/j.1360‑0443.2003.00245.x
    [Google Scholar]
  22. JohnsonR. JonesH.E. FischerG. Use of buprenorphine in pregnancy: Patient management and effects on the neonate.Drug Alcohol Depend.200370Suppl. 2S87S10110.1016/S0376‑8716(03)00062‑012738353
    [Google Scholar]
  23. GianniniE.G. TestaR. SavarinoV. Liver enzyme alteration: A guide for clinicians.CMAJ2005172336737910.1503/cmaj.104075215684121
    [Google Scholar]
  24. Di PettaG. LeonardiC.J.H.A. ProblemsR.C. Buprenorphine high-dose, broad spectrum, long-term treatment: A new clinical approach to opiate alkaloid dependency.Heroin Addict. Relat. Clin. Probl.2005732125
    [Google Scholar]
  25. GerraG. FantomaA. ZaimovicA. Naltrexone and buprenorphine combination in the treatment of opioid dependence.J. Psychopharmacol.200620680681410.1177/026988110606083516401652
    [Google Scholar]
  26. FiellinD.A. MooreB.A. SullivanL.E. BeckerW.C. PantalonM.V. ChawarskiM.C. BarryD.T. O’ConnorP.G. SchottenfeldR.S. Long-term treatment with buprenorphine/naloxone in primary care: Results at 2-5 years.Am. J. Addict.200817211612010.1080/1055049070186097118393054
    [Google Scholar]
  27. SinghR.A. MattooS.K. MalhotraA. VarmaV.K. Cases of buprenorphine abuse in India.Acta Psychiatr. Scand.1992861464810.1111/j.1600‑0447.1992.tb03224.x1414399
    [Google Scholar]
  28. LofwallM.R. StitzerM.L. BigelowG.E. StrainE.C. TreatmentT. Comparative safety and side effect profiles of buprenorphine and methadone in the outpatient treatment of opioid dependence.Addict. Disord. Their Treat.200542496410.1097/01.adt.0000145126.17405.6a
    [Google Scholar]
  29. BogenschutzM.P. AbbottP.J. KushnerR. ToniganJ.S. WoodyG.E. Effects of buprenorphine and hepatitis C on liver enzymes in adolescents and young adults.J. Addict. Med.20104421121610.1097/ADM.0b013e3181c4e27e21170166
    [Google Scholar]
  30. Al-TawilN. Odar-CederlöfI. BerggrenA.C. JohnsonH.E. PerssonJ. Pharmacokinetics of transdermal buprenorphine patch in the elderly.Eur. J. Clin. Pharmacol.201369214314910.1007/s00228‑012‑1320‑822706617
    [Google Scholar]
  31. FareedA. ScheinbergK. GaleR.B. StoutS. VayalapalliS. DrexlerK. Effect of buprenorphine on liver function tests for patients undergoing long-term maintenance treatment.Addict. Disord. Their Treat.201413313313710.1097/ADT.0b013e3182877277
    [Google Scholar]
  32. LangeW.R. FudalaP.J. DaxE.M. JohnsonR.E. Safety and side-effects of buprenorphine in the clinical management of heroin addiction.Drug Alcohol Depend.1990261192810.1016/0376‑8716(90)90078‑S2209411
    [Google Scholar]
  33. SaxonA.J. LingW. HillhouseM. ThomasC. HassonA. AngA. DoraimaniG. TasissaG. LokhnyginaY. LeimbergerJ. BruceR.D. McCarthyJ. WiestK. McLaughlinP. BilangiR. CohenA. WoodyG. JacobsP. Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: A randomized trial.Drug Alcohol Depend.20131281-2717610.1016/j.drugalcdep.2012.08.00222921476
    [Google Scholar]
  34. Ciftci DemirciA. GunesH. AdaletliH. BulanikE. ErdoganA. Liver enzyme levels in adolescent patients treated with buprenorphine and additional psychotropic agents.Am. J. Drug Alcohol Abuse201541110711310.3109/00952990.2014.98327225490611
    [Google Scholar]
  35. BersonA. FauD. FornacciariR. Degove-GoddardP. SuttonA. DescatoireV. HaouziD. LettéronP. MoreauA. FeldmannG. PessayreD. Mechanisms for experimental buprenorphine hepatotoxicity: Major role of mitochondrial dysfunction versus metabolic activation.J. Hepatol.200134226126910.1016/S0168‑8278(00)00050‑711281555
    [Google Scholar]
  36. HervéS. RiachiG. NobletC. GuillementN. TanasescuS. GoriaO. ThuillezC. TranvouezJ.L. DucrotteP. LereboursE. Acute hepatitis due to buprenorphine administration.Eur. J. Gastroenterol. Hepatol.200416101033103710.1097/00042737‑200410000‑0001315371928
    [Google Scholar]
  37. ZuinM. GiorginiA. SelmiC. BattezzatiP.M. CocchiC.A. CrosignaniA. BenettiA. InvernizziP. PoddaM. Acute liver and renal failure during treatment with buprenorphine at therapeutic dose.Dig. Liver Dis.2009417e8e1010.1016/j.dld.2007.12.01418294936
    [Google Scholar]
  38. PetryN.M. BickelW.K. PiaseckiD. MarschL.A. BadgerG.J. Elevated liver enzyme levels in opioid-dependent patients with hepatitis treated with buprenorphine.Am. J. Addict.20009326526910.1080/1055049005014809911000922
    [Google Scholar]
  39. EidenC. RipaultM.P. LarreyD. FaillieJ.L. PinzaniV. PageauxG.P. PeyrièreH. Acute hepatitis and renal failure related to intranasal buprenorphine misuse: Case report and analysis of cases reported to the French network for drug monitoring.Ann. Pharmacother.201347121721172610.1177/106002801350742924259614
    [Google Scholar]
  40. OllerD.A. ThorntonC. NuzzoP.A. FanucchiL.C. Buprenorphine induction in persons with opioid use disorder hospitalized with acute hepatitis A.J. Addict. Med.202115318719010.1097/ADM.000000000000073032909986
    [Google Scholar]
  41. McDowellML TonismaeTR SlavenJE AbernathyMP ShanksAL BenjaminTD QuinneySK The impact of hepatitis C virus infection on buprenorphine dose in pregnancy.American J. Perinatol.20203701073078
    [Google Scholar]
  42. SamarghandianS. Azimi-NezhadM. AfshariR. FarkhondehT. KarimnezhadF. Effects of buprenorphine on balance of oxidant/antioxidant system in the different ages of male rat liver.J. Biochem. Mol. Toxicol.201529624925310.1002/jbt.2169125683329
    [Google Scholar]
  43. BersonA. GervaisA. CazalsD. BoyerN. DurandF. BernuauJ. MarcellinP. DegottC. VallaD. PessayreD. Hepatitis after intravenous buprenorphine misuse in heroin addicts.J. Hepatol.200134234635010.1016/S0168‑8278(00)00049‑011281569
    [Google Scholar]
  44. KugawaF. UenoA. AokiM. Apoptosis of NG108-15 cells induced by buprenorphine hydrochloride occurs via the caspase-3 pathway.Biol. Pharm. Bull.200023893093510.1248/bpb.23.93010963298
    [Google Scholar]
  45. YazdyMM DesaiRJ BroglySB Prescription opioids in pregnancy and birth outcomes: A review of the literature.J. Pediatric Genetics.201542056070
    [Google Scholar]
  46. KuaV.M. KeanN.W. SreenivasanS. LaiN.S. Opioids in inducing cell apoptosis: A mini review.J. Biomed. Clinic. Sci.2017215361
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): Buprenorphine; lactation; liver; oxidative stress parameters; pup; rat
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