International Journal of Reproductive BioMedicine
International Journal of Reproductive BioMedicine
IJRM
Medical Sciences
http://ijrm.ir
1
admin
2476-4108
2476-3772
10.29252/ijrm
en
jalali
1403
5
1
gregorian
2024
8
1
22
8
online
1
fulltext
en
تأثیر ال-کارنیتین در کاهش گونههای اکسیژن فعال و بیان ژن آپوپتوز در موش پس از سیکلوفسفامید: یک مطالعه تجربی
The effect of L-carnitine in reactive oxygen species reduction and apoptotic gene expression in mice after cyclophosphamide: An experimental study
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:">سیکلوفسفامید (</span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، یک داروی ضد سرطان مورد استفاده، به عنوان عامل ناباروری در زنان شناخته شده است. با این وجود، ال-کارنیتین (</span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، بعنوان یک آنتی­اکسیدان، نشان داده شده است که مزایای محافظتی در برابر ناباروری دارد.</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 سطوح گونههای اکسیژن فعال (</span></span><span dir="LTR" style="font-size:10.0pt">ROS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) و بیان ژن آپوپتوز در موشهای تحت درمان با </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 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 ­ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">24 موش ماده نژاد</span></span><span dir="LTR" style="font-size:10.0pt">NMRI</span> <span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> (6 تا 8 هفته، 5</span></span> <span lang="FA" style="font-size:10.0pt">± </span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">30 گرم) به 4 گروه تقسیم شدند. گروه کنترل: نرمال سالین بصورت درون صفاقی (</span></span><span dir="LTR" style="font-size:10.0pt">IP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) به مدت 10 روز دریافت کردند. گروه </span></span><span dir="LTR" style="font-size:10.0pt">:CP</span> <span dir="LTR" style="font-size:10.0pt">mg/kg</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 75 </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را به عنوان یک تزریق </span></span><span dir="LTR" style="font-size:10.0pt">IP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در روز دهم آزمایش دریافت کردند. گروه </span></span><span dir="LTR" style="font-size:10.0pt">:LC</span> <span dir="LTR" style="font-size:10.0pt">mg/kg</span><span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> 200 </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را بصورت </span></span><span dir="LTR" style="font-size:10.0pt">IP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> به مدت 10 روز دریافت </span></span><span lang="FA" style="font-size:11.0pt"><span b="" nazanin="" style="font-family:">کردند.</span></span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:"> گروه </span></span><span dir="LTR" style="font-size:10.0pt">LC+CP</span><span lang="FA" style="font-size:10.0pt"><span b="" nazanin="" style="font-family:">: </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را به مدت 10 روز و </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بصورت تک تزریق </span></span><span dir="LTR" style="font-size:10.0pt">IP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در روز دهم آزمایش دریافت کردند. پس از 10 روز، موش­ها تحریک تخمک­گذاری شدند. سپس، لولههای رحمی موشها برداشته شد و تخمکهای هر گروه به منظور ارزیابی بیان ژن آپوپتیک </span></span><i><span dir="LTR" style="font-size:10.0pt">Bcl2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><i><span dir="LTR" style="font-size:10.0pt">Caspase3</span></i><span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">Bax</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با روش </span></span><span dir="LTR" style="font-size:10.0pt">Real-time PCR</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و سطح </span></span><span dir="LTR" style="font-size:10.0pt">ROS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> داخل سلولی با رنگ­آمیزی فلورسانس </span></span><span dir="LTR" style="font-size:10.0pt">DCFH-DA</span><span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> جمع­آوری و بررسی شد.</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:">دادهها نشان داد که </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در گروه </span></span><span dir="LTR" style="font-size:10.0pt">LC+CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بیان ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">Bcl2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را بهطور معنیداری افزایش داد (01/0 </span></span><span lang="FA" 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 بیان ژنهای </span></span><i><span dir="LTR" style="font-size:10.0pt">Bax</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">Caspase3</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را نسبت به گروه </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> کاهش داد (03/0 </span></span><span lang="FA" 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 04/0 </span></span><span lang="FA" 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 </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> سطح </span></span><span dir="LTR" style="font-size:10.0pt">ROS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را در گروه </span></span><span dir="LTR" style="font-size:10.0pt">LC+CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> نسبت به گروه </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> کاهش داد (001/0 </span></span><span lang="FA" 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 گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">یافتهها نشان میدهد که </span></span><span dir="LTR" style="font-size:10.0pt">LC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> میتواند </span></span><span dir="LTR" style="font-size:10.0pt">ROS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ناشی از </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را از بین ببرد و مسیر آپوپتوز را از طریق کاهش بیان ژنهای </span></span><i><span dir="LTR" style="font-size:10.0pt">Bax</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">Caspase3</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و افزایش بیان ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">Bcl2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در تخمک موشهای در معرض </span></span><span dir="LTR" style="font-size:10.0pt">CP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تعدیل کند.</span></span></span></span></span></span></span></div>
<div style="text-align: justify;"><span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="background:white">Background:</span></b> Cyclophosphamide (CP), a utilized anticancer drug, is known to cause infertility in women. However, L-carnitine (LC), an antioxidant, has been shown to offer protective benefits against infertility.</span></span><br>
<span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b>Objective:</b> This study aimed to evaluate the levels of reactive oxygen species (ROS) and apoptotic gene expression in mice treated with CP and LC.</span></span><br>
<span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b>Materials and Methods: </b>24 NMRI female mice (6-8 wk, 30 ± 5 gr) were divided into 4 groups: control group: received normal saline intraperitoneal (IP) injection for 10 days; CP group: received 75 mg/kg of CP as a single IP on the 10<sup>th</sup> day of the experiment; LC group: received 200 mg/kg of LC IP for 10 days; LC+CP group: received LC for 10 days and CP single IP injection on the 10<sup>th</sup> day of the experiment. After 10 days, mice were superovulated. The oviducts were then removed, and the oocytes of each group were collected for evaluating apoptotic gene expression B-cell lymphoma 2<i> </i>(<i>Bcl2</i>), <i>Bcl2</i>-associated X<i> </i>(<i>Bax</i>), and <i>Caspase3</i> via real-time polymerase chain reaction and intracellular ROS levels by dichloro-dihydro-fluorescein diacetate fluorescence staining.</span></span><br>
<span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b>Results:</b><b> </b>Data revealed that LC in the LC+CP group significantly increased <i>Bcl2</i> gene expression (p = 0.01), and decreased <i>Bax</i> and <i>Caspase3</i> gene expression compared to the CP group (p = 0.03, p = 0.04). LC decreased the ROS level in the LC+CP group compared to the CP group (p < 0.001).</span></span><br>
<span style="font-size:12pt"><span new="" roman="" style="font-family:" times=""><b>Conclusion: </b>Findings suggest that LC can scavenge the ROS caused by CP and modulate the apoptotic pathway via downregulating the <i>Bax</i> and <i>Caspase3</i> genes and upregulating the <i>Bcl2</i> gene in oocytes of mice exposed to CP.</span></span></div>
کارنیتین, سیکلوفسفامید, آپوپتوز, ژنها, گونههای فعال اکسیژن.
Carnitine, Cyclophosphamide, Apoptosis, Genes, Reactive oxygen species.
661
672
http://ijrm.ir/browse.php?a_code=A-10-2739-1&slc_lang=en&sid=1
Majid
Almasi
majid.almasi72@gmail.com