Volume 22, Issue 7 (July 2024)                   IJRM 2024, 22(7): 515-526 | Back to browse issues page

Ethics code: IR.MAZUMS..REC.1398.5488


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Akbarzadeh M, Ataee R, Nemati F, Depouri A A, Shaki F. Melatonin's protective effect against placental transfer of Methadone in mice: An experimental study. IJRM 2024; 22 (7) :515-526
URL: http://ijrm.ir/article-1-3257-en.html
1- Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Qaemshahr Branch, Qaemsharh, Iran.
2- Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
3- Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Qaemshahr Branch, Qaemsharh, Iran. , farkhondehnemati@gmail.com
4- Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract:   (415 Views)
Background: Methadone is a substance widely used in the substitution treatment of opiate addiction in pregnancy. The placental transfer of methadone influences oxidative stress processes. Melatonin is a hormone with antioxidant activity.
Objective: This study aimed to evaluate the protective effects of melatonin on oxidative stress induced by the transfer of transplacental methadone in mice.
Materials and Methods: In this experimental study, 36 female mice (2 months old, 20 ± 2 gr) were divided into 6 groups (n = 6/each) of control, methadone (0.3 mg/kg intraperitoneal, single dose) and melatonin (2, 4, and 6 mg/kg/day gavage) were administered 30 min before methadone, and one group received melatonin alone (0.6 mg/kg with single injection). Administration for 10 consecutive days of the pregnancy period was done. After baby mice were born, all neonatal mice were killed by beheading or sacrificing after anesthesia. The liver tissues were extracted. The samples were then sent for studying oxidative stress markers such as lipid peroxidation, glutathione, and protein carbonyl contents. Also, we have used the immunohistochemistry method for apoptotic markers such as: BAX, Bcl2, and Caspase3 for assaying apoptosis.
Results: This study has shown that methadone caused a significant decrease in glutathione concentration (p = 0.035). Also, we observed a significant increase in lipid peroxidation and protein carbonyl contents (p = 0.015, 0.025 respectively). However, melatonin treatment significantly inhibited oxidative stress markers (p = 0.025). Also, apoptosis assay has shown that melatonin could decrease BAX and Caspase 9 as apoptotic and increase Bcl2 as an antiapoptotic proteins (p = 0.015).
Conclusion: Our findings have shown that melatonin has a protective effect against oxidative stress and apoptosis induced by the placental transfer of methadone via its antioxidant effects.
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Type of Study: Original Article | Subject: Reproductive Biology

References
1. Volpe DA, Xu Y, Sahajwalla ChG, Younis IR, Patel V. Methadone metabolism and drug-drug interactions: In vitro and in vivo literature review. J Pharm Sci 2018; 107: 2983-2991. [DOI:10.1016/j.xphs.2018.08.025] [PMID]
2. Sharpe C, Kuschel C. Outcomes of infants born to mothers receiving methadone for pain management in pregnancy. Arch Dis Child Fetal Neonatal Ed 2004; 89: 33-36. [DOI:10.1136/fn.89.1.F33] [PMID] [PMCID]
3. Farid WO, Dunlop SA, Tait RJ, Hulse GK. The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: Review of human and animal data. Curr Neuropharmacol 2008; 6: 125-150. [DOI:10.2174/157015908784533842] [PMID] [PMCID]
4. Shahraz S, Ghaziany T. [Iran farma, comprehensive drug official]. 4th Ed. Tehran: Tymurzadeh Pub; 2007. (in Persian)
5. Diane S, Aschenbrenner MS, Aprn BC. Drug therapy in nursing. 3rd Ed. Philadelphia: Lippincott Williams & Wilkins; 2004.
6. Khalilieh S, Yee KL, Sanchez RI, Vaynshteyn K, Fan L, Searle S, et al. Evaluation of the pharmacokinetic interaction between doravirine and methadone. Clin Pharmacol Drug Dev 2020; 9: 151-161. [DOI:10.1002/cpdd.699] [PMID]
7. Corkery JM, Schifano F, Ghodse AH, Oyefeso A. The effects of methadone and its role in fatalities. Hum Psychopharmacol 2004; 19: 565-576. [DOI:10.1002/hup.630] [PMID]
8. Methadone Official FDA information. Side effects and uses. Available at: http://www.drugs.com/pro/methadone.html.
9. Katzung BG. Basic and clinical pharmacology. 9th Ed. New York: McGraw Hill; 2004.
10. Ito S. Opioids in breast milk: Pharmacokinetic principles and clinical implications. J Clin Pharmacol 2018; 58 (Suppl.): S151-S163. [DOI:10.1002/jcph.1113] [PMID]
11. Lopes C, Luna SP, Rosa AC, Quarterone C, Crosignani N, Taylor PM, et al. Antinociceptive effects of methadone combined with detomidine or acepromazine in horses. Equine Vet J 2016; 48: 613-618. [DOI:10.1111/evj.12483] [PMID]
12. Van den Anker J. Is it time to replace morphine with methadone for the treatment of pain in the neonatal intensive care unit? Pediatr Res 2021; 89: 1608-1609. [DOI:10.1038/s41390-021-01472-z] [PMID] [PMCID]
13. Harrison TK, Kornfeld H, Aggarwal AK, Lembke A. Perioperative considerations for the patient with opioid use disorder on buprenorphine, methadone, or naltrexone maintenance therapy. Anesthesiol Clin 2018; 36: 345-359. [DOI:10.1016/j.anclin.2018.04.002] [PMID]
14. Nanovskaya TN, Nekhayeva IA, Hankins GD, Ahmed MS. Transfer of methadone across the dually perfused preterm human placental lobule. Am J Obstet Gynecol 2008; 198: 126. [DOI:10.1016/j.ajog.2007.06.073] [PMID]
15. Salarian A, Kadkhodaee M, Zahmatkesh M, Seifi B, Bakhshi E, Akhondzadeh S, et al. Opioid use disorder induces oxidative stress and inflammation: The attenuating effect of methadone maintenance treatment. Iran J Psychiatry 2018; 13: 46-54.
16. Mohamed ShS, El-Desouky TA, Mohamed ShR, Naguib KhM, Helmy MH. Antioxidant compounds from rice straw extract and their effect on diazinon insecticide hazard. Middle East J Appl Sci 2015; 5: 687-694.
17. Di Meo S, Venditti P. Evolution of the knowledge of free radicals and other oxidants. Oxid Med Cell Longev 2020; 23: 9829176. [DOI:10.1155/2020/9829176] [PMID] [PMCID]
18. Parisotto EB, Vidal V, García-Cerro S, Lantigua S, Wilhelm Filho D, Sanchez-Barceló EJ, et al. Chronic melatonin administration reduced oxidative damage and cellular senescence in the hippocampus of a mouse model of Down syndrome. Neurochem Res 2016; 41: 2904-2913. [DOI:10.1007/s11064-016-2008-8] [PMID]
19. Crupi R, Palma E, Siracusa R, Fusco R, Gugliandolo E, Cordaro M, et al. Protective effect of hydroxytyrosol against oxidative stress induced by the ochratoxin in kidney cells: In vitro and in vivo study. Front Vet Sci 2020; 7: 136. [DOI:10.3389/fvets.2020.00136] [PMID] [PMCID]
20. Mayo JC, Sainz RM. Melatonin from an antioxidant to a classic hormone or a tissue factor: Experimental and clinical aspects 2019. Int J Mol Sci 2020; 21: 3645-3648. [DOI:10.3390/ijms21103645] [PMID] [PMCID]
21. Morvaridzadeh M, Sadeghi E, Agah Sh, Nachvak SM, Fazelian S, Moradi F, et al. Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis. Pharmacol Res 2020; 161: 105210-105215. [DOI:10.1016/j.phrs.2020.105210] [PMID]
22. Zhang F, Xu Zh, Gao J, Xu B, Deng Y. In vitro effect of manganese chloride exposure on energy metabolism and oxidative damage of mitochondria isolated from rat brain. Environ Toxicol Pharmacol 2008; 26: 232-236. [DOI:10.1016/j.etap.2008.04.003] [PMID]
23. Sadegh C, Schreck RP. The spectroscopic determination of aqueous sulfite using Ellman's reagent. MURJ 2003; 8: 39-43.
24. Barreiro E. Role of protein carbonylation in skeletal muscle mass loss associated with chronic conditions. Proteomes 2016; 4: 18-20. [DOI:10.3390/proteomes4020018] [PMID] [PMCID]
25. Zinellu E, Zinellu A, Fois AG, Carru C, Pirina P. Circulating biomarkers of oxidative stress in chronic obstructive pulmonary disease: A systematic review. Respir Res 2016; 17: 150-155. [DOI:10.1186/s12931-016-0471-z] [PMID] [PMCID]
26. Ataee R, Ajdary S, Rezayat M, Shokrgozar MA, Shahriari S, Zarrindast MR. Study of 5HT3 and HT4 receptor expression in HT29 cell line and human colon adenocarcinoma tissues. Arch Iran Med 2010; 13: 120-125.
27. Sciuto AM. Antioxidant properties of glutathione and its role in tissue protection. In: Baskin SI, Salem H. Oxidants, antioxidants, and free radicals. USA: CRC Press; 2017: 171-191. [DOI:10.1201/9780203744673-9]
28. Leventelis C, Goutzourelas N, Kortsinidou A, Spanidis Y, Toulia G, Kampitsi A, et al. Buprenorphine and methadone as opioid maintenance treatments for heroin-addicted patients induce oxidative stress in blood. Oxid Med Cell Longev 2019; 2019: 9417048. [DOI:10.1155/2019/9417048] [PMID] [PMCID]
29. Root-Bernstein R, Churchill B, Turke M. Glutathione and glutathione-like sequences of opioid and aminergic receptors bind ascorbic acid, adrenergic and opioid drugs mediating antioxidant function: Relevance for anesthesia and abuse. Int J Mol Sci 2020; 21: 6230-6235. [DOI:10.3390/ijms21176230] [PMID] [PMCID]
30. Xu Ch, Chen X, Reece EA, Lu W, Yang P. The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy. Am J Obstet Gynecol 2019; 220: 108-110. [DOI:10.1016/j.ajog.2018.10.001] [PMID] [PMCID]
31. Ali SS, Ahsan H, Zia MK, Siddiqui T, Khan FH. Understanding oxidants and antioxidants: Classical team with new players. J Food Biochem 2020; 44: e13145. [DOI:10.1111/jfbc.13145]
32. Shivananjappa MM. Abrogation of maternal and fetal oxidative stress in the streptozotocin-induced diabetic rat by dietary supplements of Tinospora cordifolia. Nutrition 2012; 28: 581-587. [DOI:10.1016/j.nut.2011.09.015] [PMID]
33. Goh S-Y, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93: 1143-1152. [DOI:10.1210/jc.2007-1817] [PMID]
34. Da Pozzo E, De Leo M, Faraone I, Milella L, Cavallini C, Piragine E, et al. Antioxidant and antisenescence effects of bergamot juice. Oxid Med Cell Longev 2018; 2018: 9395804. [DOI:10.1155/2018/9395804] [PMID] [PMCID]
35. Alkadi H. A review on free radicals and antioxidants. Infect Disord Drug Targets 2020; 20: 16-26. https://doi.org/10.2174/22123989OTEznMzIwTcVY [DOI:10.2174/1871526518666180628124323] [PMID]
36. Gibson JM, Chu T, Zeng W, Wethall AC, Kong M, Mellen N, et al. Perinatal methadone exposure attenuates myelination and induces oligodendrocyte apoptosis in neonatal rat brain. Exp Biol Med 2022; 247: 1067-1079. [DOI:10.1177/15353702221090457] [PMID] [PMCID]
37. Van Cutsem E, TAX 325 study group. Docetaxel in gastric cancer. EJC Supplements 2004; 2: 52-58. [DOI:10.1016/j.ejcsup.2004.04.016]
38. Mannino G, Pernici C, Serio G, Gentile C, Bertea CM. Melatonin and phytomelatonin: Chemistry, biosynthesis, metabolism, distribution and bioactivity in plants and animals-an overview. Int J Mol Sci 2021; 22: 9996. [DOI:10.3390/ijms22189996] [PMID] [PMCID]
39. Pakravan H, Ahmadian M, Fani A, Aghaee D, Brumanad S, Pakzad B. The effects of melatonin in patients with nonalcoholic fatty liver disease: A randomized controlled trial. Adv Biomed Res 2017; 6: 40. [DOI:10.4103/2277-9175.204593] [PMID] [PMCID]
40. Najafi M, Cheki M, Hassanzadeh G, Amini P, Shabeeb D, Musa AE. Protection from radiation-induced damage in rat's ileum and colon by combined regimens of melatonin and metformin: A histopathological study. Antiinflamm Antiallergy Agents Med Chem 2020; 19: 180-189. [DOI:10.2174/1871523018666190718161928] [PMID] [PMCID]
41. Santiago J, Silva JV, Santos MAS, Fardilha M. Fighting bisphenol A-induced male infertility: The power of antioxidants. Antioxidants 2021; 10: 289-291. [DOI:10.3390/antiox10020289] [PMID] [PMCID]

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