en اثر محافظتی ملاتونین در برابر انتقال جفت متادون در موش: یک مطالعه تجربی Reproductive Biology Original Article Original Article <div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">متادون بعنوان درمان جایگزینی اعتیاد به مواد افیونی به طور گسترده در بارداری استفاده می&shy;شود. انتقال جفتی متادون بر فرآیندهای استرس اکسیداتیو تأثیر می&shy;گذارد. ملاتونین هورمونی با فعالیت آنتی&shy;اکسیدانی می&shy;باشد.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">این مطالعه با هدف بررسی اثرات محافظتی ملاتونین بر استرس اکسیداتیو ناشی از انتقال متادون از طریق جفت در موش سوری انجام شد.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مواد و روش &shy;ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در این مطالعه تجربی، 36 موش ماده (2 ماهه، 2 </span></span><span lang="FA" style="font-size:10.0pt">&plusmn;</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 20 گرم) به 6 گروه تقسیم شدند (هر گروه 6 موش): کنترل، متادون (3/0 میلی‌گرم بر کیلوگرم داخل صفاقی) و ملاتونین (2، 4 ،6) میلی‌گرم بر کیلوگرم در روز گاواژ) 30 دقیقه قبل و یک گروه هم ملاتونین (یک تک دوز 6/0 میلی‌گرم بر کیلوگرم) دریافت کردند. تجویز برای ده روز متوالی از دوره بارداری انجام شد. پس از تولد نوزاد موش، تمام موش&shy;های نوزاد با سر بریدن کشته شدند. سپس، بافت‌های کبد، مغز و کلیه جدا شدند و برای ارزیابی نشانگرهای استرس اکسیداتیو، از جمله پراکسیداسیون لیپیدی، گلوتاتیون و محتوای کربونیل پروتئین مورد استفاده قرار گرفتند.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">این مطالعه نشان داد که متادون باعث کاهش معنی‌دار غلظت گلوتاتیون شد (035/0 </span></span><span dir="LTR" style="font-size:10.0pt">=</span> <span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">). همچنین افزایش معنی&shy;داری در میزان پراکسیداسیون لیپیدی و محتوای پروتئین کربونیل (به ترتیب 015/0 </span></span><span dir="LTR" style="font-size:10.0pt">=</span> <span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و 025/0 </span></span><span dir="LTR" style="font-size:10.0pt">=</span> <span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) مشاهده شد. با این حال، درمان ملاتونین به طور قابل توجهی نشانگرهای استرس اکسیداتیو را مهار کرد (025/0 </span></span><span dir="LTR" style="font-size:10.0pt">=</span> <span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) همچنین نتایج بررسی آپوپتوز نشان داد که ملاتونین باعث کاهش</span></span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">بیان</span></span><span dir="LTR" style="font-size:10.0pt">BAX</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">&nbsp;و</span></span><span dir="LTR" style="font-size:10.0pt">Caspase 9 </span>&nbsp;<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و افزایش</span></span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">بیان</span></span><span dir="LTR" style="font-size:10.0pt">Bcl2</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">&nbsp;به عنوان یک فاکتور آنتی</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">آپوپتیک گردید (015/0 </span></span><span dir="LTR" style="font-size:10.0pt">=</span> <span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">).</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتیجه &shy;گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">یافته‌های ما نشان داد که ملاتونین دارای اثر محافظتی در برابر استرس اکسیداتیو و آپوپتوز ناشی از انتقال جفتی متادون می&shy;باشد.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> &nbsp;</div> <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Background:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> 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.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Objective:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> This study aimed to evaluate the protective effects of melatonin on oxidative stress induced by the transfer of transplacental methadone in mice.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> In this experimental study, 36 female mice (2 months old, 20 &plusmn; 2 gr) were divided into 6 groups (n = 6/each) of control, methadone (0.3 mg/kg intraperitoneal, single dose) and melatonin <a name="_Hlk152053681">(2, 4, and 6 mg/kg/day gavage)</a> 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 </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">sacrificing after anesthesia</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">. 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.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Results:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> 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 </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">= 0.025)</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">. 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).</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> 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.</span></span></span></span></span></span></span></div> استرس اکسیداتیو, متادون, ملاتونین, بارداری. Oxidative stress, Methadone, Melatonin, Pregnancy. 515 526 http://ijrm.ir/browse.php?a_code=A-10-2175-1&slc_lang=en&sid=1 Maryam Akbarzadeh MaryamAkbarzadeh@gmail.com 0000-0002-9496-9706 No Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Qaemshahr Branch, Qaemsharh, Iran. Ramin Ataee raminataee1349@gmail.com 0000-0002-6342-0382 No Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Farkhondeh Nemati farkhondehnemati@gmail.com 0000-0002-3674-2087 Yes Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Qaemshahr Branch, Qaemsharh, Iran. Abbas Ali Depouri dehpour@gmail.com 0000-0002-7515-7569 No Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Qaemshahr Branch, Qaemsharh, Iran. Fatemeh Shaki FatemehShaki@gmail.com : 0000-0001-5861-656X No Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.