en تیموکینون سمیت تولید مثلی ناشی از آکریل آمید را در موش های صحرایی ماده بهبود می بخشد: 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:">آکریل آمید (</span></span><span dir="LTR" style="font-size:10.0pt">AA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) یک ترکیب سرطان</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:">زا است که باعث اختلالات شدید تولید</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:">مثل می</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:">شود و یک عامل خطر زیست محیطی بالا را نشان می</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:">دهد. تیموکینون </span></span><span dir="LTR" style="font-size:10.0pt">(TQ)</span><span style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> دارای یک فعالیت آنتی&shy;اکسیدانی منحصر به فرد بوده و به طور گسترده&shy;ای به عنوان یک عامل محافظ در برابر انواع مختلف سمیت استفاده می&shy;شود.</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:">هدف<b> </b>ارزیابی اثرات محافظتی </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در برابر سمیت تولید</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:">مثلی ناشی از </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در موش‌های ماده بود.</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:">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، 40 سر موش صحرایی ماده آلبینو (150-120 گرم، 8-10 هفته) در 4 گروه (هر کدام 10 سر) دسته‌بندی شدند. گروه کنترل (دریافت خوراکی روزانه 5/0 میلی&shy;لیتر سالین [9</span></span><span lang="FA" style="font-size:11.0pt"><span majalla="" sakkal="" style="font-family:">٪</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">])؛ گروه </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">(دریافت خوراکی روزانه </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">تازه تهیه شده، 20 میلی</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:">گرم بر کیلوگرم وزن بدن به مدت 21 روز) که کمتر از دوز کشنده </span></span><span dir="LTR" style="font-size:10.0pt">LD50 AA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در موش</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:">ها (20 میلی&shy;گرم بر کیلوگرم وزن بدن) است. گروه </span></span><span dir="LTR" style="font-size:10.0pt">AA+TQ</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> (دریافت خوراکی روزانه </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، 10 میلی گرم بر کیلوگرم وزن بدن پس از مسمومیت با </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">به مدت 21 روز)، و گروه </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">(دریافت خوراکی روزانه </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">تنها، 10 میلی</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:">گرم بر کیلوگرم وزن بدن برای 21 روز متوالی). هورمون‌های تولید&shy;مثلی، بیومارکرهای سرطان‌زا و نشانگرهای استرس اکسیداتیو اندازه‌گیری شدند. ارزیابی بافت&shy;شناسی اثر محافظتی </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در برابر آسیب تخمدان ناشی از </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">را نشان داد. تجزیه و تحلیل فارماکولوژی شبکه و رویکرد اتصال مولکولی برای تعیین میل اتصال </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">با سیکلواکسیژناز 2 انجام 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:">تجویز </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">به طور قابل توجهی ظرفیت عملکردی تخمدان را در هورمون‌ها، بیومارکرهای اکسیداتیو و نشانگرهای تومور در سطح معنی‌داری 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:"> افزایش داد. علاوه بر این، </span></span><span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">از تخمدان موش</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:">های تحت درمان با </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در برابر اثر تخریب شدید محافظت می</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:">کند.</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:">نتیجه&shy;گیری:</span></span></b> <span dir="LTR" style="font-size:10.0pt">TQ</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">اثر محافظتی امیدوارکننده‌ای در برابر سمیت تولید</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:">مثلی ناشی از </span></span><span dir="LTR" style="font-size:10.0pt">AA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در موش‌های ماده نشان داد.</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></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 calibri="" style="font-family:"><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=""> Acrylamide (AA) is a carcinogenic compound that causes severe reproductive impairments and represents a high environmental risk factor. Thymoquinone (TQ) has a unique antioxidant activity and has been widely used as a protective agent against various types of toxicity. </span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><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=""> To evaluate the protective effects of TQ against AA-induced reproductive toxicity in female rats.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><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, 40 female albino rats (120-150 gr, 8-10 wk) were sorted into 4 groups, (n = 10/each), </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">vehicle</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> group (received a daily oral administration of 0.5 ml saline [9%]); AA group (received a daily oral administration with freshly prepared AA, 20 mg/kg body weight) for 21 days which is less than the lethal dose LD₅₀ of AA in rats (20 mg /kg body weight); AA+TQ group (received a daily oral administration of TQ, 10 mg/kg body weight) after AA intoxication for 21 days, and TQ group (received a daily oral administration of TQ only, 10 mg/kg body weight) for 21 consecutive days. Reproductive hormones, carcinogenic biomarkers<span style="background:white">, and </span>oxidative stress markers were measured. The histological assessment showed the protective effect of TQ against AA-induced ovarian injury. Network pharmacology analysis and molecular docking approach were carried out to determine the binding affinity of TQ with cyclooxygenase 2. </span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><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=""> TQ administration significantly enhanced the functional capacity of the ovary at hormones, oxidative biomarkers, and tumor markers at a significant level of p < 0.001. Besides, TQ protects the ovary of AA-treated rats from the severe degeneration effect.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><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=""> <span class="fontstyle21" new="" roman="" style="font-family:" times=""><span style="color:black"><span style="font-weight:bold"><span style="font-style:normal"><span style="font-weight:normal">TQ showed a promising protective effect </span></span></span></span></span>against AA-induced reproductive toxicity in female rats.<span class="fontstyle21" new="" roman="" style="font-family:" times=""><span style="color:black"><span style="font-weight:bold"><span style="font-style:normal"><span style="font-weight:normal"></span></span></span></span></span></span></span></span></span></span></span></div> آکریل آمید, تیموکینون, موش صحرایی, استرس اکسیداتیو, سیکلواکسیژناز 2, التهاب. Acrylamide, Thymoquinone, Rats, Oxidative stress, Cyclooxygenase 2, Inflammation. 61 70 http://ijrm.ir/browse.php?a_code=A-10-1901-1&slc_lang=en&sid=1 Maryam AL-ghamdi maaalghamdi3@kau.edu.sa 0000-0003-0861-953X No Department of Biochemistry, Faculty of Science, King AbdulAziz University, Jeddah, Saudi Arabia. Experimental Biochemistry Unit, King Fahad Medical Research Centre, King AbdulAziz University, Jeddah, Saudi Arabia. Vitamin D Pharmacogenomics Research Group, King AbdulAziz University, Saudi Arabia. Etimad Huwait ehuwait@kau.edu.sa 0000-0002-4657-6668 No Department of Biochemistry, Faculty of Science, King AbdulAziz University, Jeddah, Saudi Arabia. Experimental Biochemistry Unit, King Fahad Medical Research Centre, King AbdulAziz University, Jeddah, Saudi Arabia. Nagwa Elsawi elsawinagwa@yahoo.com 0000-0002-0918-6548 No Department of Chemistry, Lab Biochemistry, Faculty of Science, Sohag University, Sohag, Egypt. Soad Shaker Ali Sabdulhadi@kau.edu.sa 0000-0003-1976-5903 No Faculty of Medicine, Merit University, Sohag, Egypt. Ahmed Sayed ahmed.sayed@aun.edu.eg 0000-0002-3349-2545 Yes Biochemistry Laboratory, Faculty of Science, Chemistry Department, Assiut University, Assiut, Egypt.