تغییرات بیان ژن KRAS مرتبط با نانوذرات نقره (AgNPs)

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه داروشناسی، دانشکده پزشکی، دانشگاه علوم پزشکی و داروسازی ابن‌سینا، بغداد، عراق

2 دانشکده علوم مهندسی کشاورزی، دانشگاه بغداد، عراق

3 گروه بیوتکنولوژی، دانشکده علوم، دانشگاه الانبار، عراق

10.22103/jab.2025.24920.1672

چکیده

هدف: فناوری نانو انقلابی در حوزه‌های مختلف از جمله پزشکی، لوازم آرایشی و بسته‌بندی مواد غذایی ایجاد کرده است، به‌ویژه از طریق استفاده از نانومواد مهندسی‌شده مانند نانوذرات نقره (AgNPs). نانوذرات نقره به دلیل خواص ضد میکروبی قوی، از پرکاربردترین نانوذرات در محصولات مصرفی و زیست‌پزشکی محسوب می‌شوند. این مطالعه با هدف بررسی اثرات نانوذرات نقره بر سطح بیان ژن سرطان‌زای ویروسی Kirsten rat sarcoma (KRAS) در بافت‌های کبد و طحال موش‌ها انجام شد تا ایمنی مولکولی تماس با AgNPs ارزیابی شود.
مواد و روش‌ها: در مجموع ۵۶ موش به‌صورت تصادفی به هفت گروه (n=8 در هر گروه) تقسیم شدند. سه گروه به‌مدت ۷ روز مقادیر 25/0، 5/0 و 1 میلی‌گرم بر کیلوگرم وزن بدن AgNP دریافت کردند. سه گروه دیگر همان دوزها را به‌مدت ۱۴ روز دریافت کردند. یک گروه نیز به عنوان کنترل بدون درمان باقی ماند. پس از پایان دوره درمان، بافت‌های کبد و طحال جمع‌آوری شد. RNA کل با استفاده از روش جونکویرا و کارنیرو استخراج و سنتز cDNA با استفاده از کیت Applied Biosystem به شماره 4387406 برای آنالیز بیان ژن انجام شد.
نتایج: سطح بیان ژن KRAS بسته به دوز و مدت‌زمان تماس با AgNPها متفاوت بود. در بافت کبد، بیان ژن KRAS در همه گروه‌های دریافت‌کننده AgNP نسبت به گروه کنترل کاهش یافت. در مقابل، در بافت طحال، بیان ژن KRAS در تمام گروه‌های دریافت‌کننده به‌طور قابل‌توجهی افزایش داشت. این تغییرات در دوزهای بالاتر و مدت تماس طولانی‌تر شدیدتر بودند.
نتیجه‌گیری: یافته‌ها نشان می‌دهند که تماس با AgNPها باعث تنظیم مجدد بیان ژن KRAS به‌صورت مختص-بافتی می‌شود؛ به‌طوری‌که کاهش بیان در بافت کبد و افزایش بیان در بافت طحال مشاهده شد. این الگوهای متفاوت بیان بیانگر آن هستند که نانوذرات نقره ممکن است مسیرهای پیام‌رسانی سلولی را به شیوه‌ای تحت تأثیر عملکرد اندام‌ها و ریزمحیط‌ها تغییر دهند. به‌ویژه، افزایش مداوم بیان KRAS در طحال پس از مصرف AgNPها، به‌ویژه در دوزهای بالا و تماس طولانی‌مدت نگرانی‌هایی جدی درباره اختلالات ایمنی یا آغاز فرآیندهای سرطان‌زایی در بافت‌های مرتبط با سیستم ایمنی ایجاد می‌کند. این نتایج لزوم ارزیابی دقیق‌تر استفاده از AgNPها را به‌ویژه در محصولاتی که برای کاربرد طولانی‌مدت یا سیستمیک طراحی شده‌اند، نشان می‌دهد. مطالعات بیشتری برای روشن‌سازی مکانیسم‌های زیربنایی تنظیم KRAS توسط AgNPها، ارزیابی پیامدهای آسیب‌شناسی احتمالی بلندمدت، و تعیین آستانه‌های ایمن تماس ضروری است. تهیه یک پروفایل جامع ایمنی مولکولی برای تضمین توسعه و استفاده مسئولانه از فناوری‌های مبتنی بر نانوذرات نقره در حوزه‌های پزشکی و تجاری حیاتی است.

کلیدواژه‌ها

عنوان مقاله [English]

β-ACTIN, gene expression, liver, silver nanoparticles, spleen

نویسندگان [English]

  • Mohammed Ayyed Najm 1
  • Gulboy Abdolmajeed Nasir 2
  • Huda Musleh Mahmood 3
1 Department of Pharmacology, College of Medicine, Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq
2 College of Agricultural Engineering Sciences, University of Baghdad, Iraq.
3 Department of Biotechnology, College of Sciences, University of Anbar, Iraq
چکیده [English]

Objective
Nanotechnology has revolutionized various fields, including medicine, cosmetics, and food packaging, through the incorporation of engineered nanomaterials such as silver nanoparticles (AgNPs). Due to their potent antimicrobial properties, AgNPs are among the most widely utilized nanoparticles in consumer and biomedical products. This study aimed to investigate the effects of AgNPs on the expression levels of the Kirsten rat sarcoma viral oncogene (KRAS) in hepatic and splenic tissues of mice, in order to assess the molecular safety of AgNP exposure.

Materials and Methods
A total of 56 mice were randomly divided into seven groups (n=8 per group). Three groups received AgNPs at doses of 0.25, 0.5, and 1 mg/kg body weight daily for 7 days. Another three groups were administered the same respective doses for 14 days. One group served as an untreated control. Following treatment, liver and spleen tissues were harvested. Then total RNA was extracted using Junqueira and Carneiro's method and cDNA was synthesized using the Applied Biosystem, Part No. 4387406 kit for quantitative gene expression analysis.

Results
KRAS gene expression levels were found to vary depending on both the dosage and duration of AgNP exposure. In liver tissues, KRAS expression was reduced across all AgNP-treated groups compared to the control. Conversely, splenic KRAS expression was consistently elevated in treated groups relative to the control. These changes were more pronounced with higher doses and longer exposure durations.

Conclusions
The results suggest that AgNP exposure modulates KRAS gene expression in a tissue-specific manner, with downregulation observed in hepatic tissue and upregulation in splenic tissue. These differential expression patterns indicate that AgNPs may influence cellular signaling pathways in a manner dependent on organ function and microenvironment. Notably, the consistent upregulation of KRAS in the spleen following AgNP administration—especially at higher doses and prolonged exposure—raises important concerns regarding potential immunological disturbances or the initiation of oncogenic processes in immune-related tissues. These findings underscore the need for cautious evaluation of AgNP use, particularly in products designed for long-term or systemic application. Further studies are warranted to elucidate the underlying mechanisms of KRAS modulation by AgNPs, assess potential long-term pathological consequences, and determine safe exposure thresholds. Comprehensive molecular safety profiling is essential to ensure the responsible development and use of silver nanoparticle-based technologies in both medical and commercial contexts.

کلیدواژه‌ها [English]

  • β-ACTIN
  • gene expression
  • liver
  • silver nanoparticles
  • spleen

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مجله بیوتکنولوژی کشاورزی
دوره 17، شماره 2
اردیبهشت 1404
صفحه 217-236

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