Razi Journal of Medical Sciences

fa بررسی سمیت انتخابی نانوذرات کورکومین لود شده درآهن بر روی سلول‌های فیبروبلاست ایزوله شده از پوست مدل حیوانی زخم پای دیابتی Investigating the Selective Toxicity of Iron-Loaded Curcumin Nanoparticles on Fibroblast Cells Isolated from the Skin of an Animal Model of Diabetic Foot Ulcer بیولوژی (زیست شناسی) Biology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: زخم پای دیابتی بیماری رایجی در میان بیماران مبتلا به دیابت نوع ۱ و ۲ می‌باشد که معمولا با وارد شدن یک آسیب هرچند جزئی به پاها ایجاد می‌شود. درمان این زخم‌ها در افرادی که مبتلا به دیابت نیستند معمولا خود به خودی انجام می شود اما در مورد بیماران دیابتی رسیدگی سریع و توجه به این زخم امری ضروری می‌باشد. کورکومین ماده فعال زردچوبه که  دارای ویژگی‌های ضد التهابی، آنتی اکسیدانی، ضد دیابـتی و ضـد سـرطانی می‌باشد به علت حلالیت کم در آب، استفاده از خواص دارویی و بیولوژیکی آن محدود شده است، اما امروزه برای بهبود عملکرد کورکومین محققین توانسته‌اند که ساختارهای نانوذرات این ترکیب را بسازند و یا در نانوذرات پرکاربرد لود بکنند. میزان کاربرد نانوذرات پس از سنتز اغلب توسط مطالعات سلولی در مکانیسم استرس اکسیداتیو نشان داده می‌شود. روش کار: ما نانوذرات اکسید آهن سوپرپارامغناطیس بارگذاری شده با کورکومین (Fe3O4 magnetic- CurNPs)  را برای دستیابی به یک اثر کمک درمانی طراحی کردیم. خواص فیزیکوشیمیایی نانوذرات مغناطیسی Fe3O4 با استفاده از پراش پرتو ایکس (XRD) و پراکندگی نور لیزر (DLS) پویا و پتانسیل زتا مشخص شد. علاوه بر این، برای اثبات میزان سمیت سلولی  فاکتورهای سلولی مانند زنده مانی سلولی، تولید گونه‌های فعال اکسیژن (ROS)، تغییرات پراکسیداسیون لیپیدی و آزادسازی سیتوکروم c همچنین تغییرات هیستوپاتولوژی در بافت پوست را مشخص نمودیم. یافته‌ها: پژوهش پیش رو نشان دادیم که درمان موثر با نانوذرات باعث کاهش یا جلوگیری از استرس اکسیداتیو و اختلال عملکرد میتوکندری در پوست حیوانات تحت مطالعه می‌شود، همچنین میزان زنده مانی سلولی به طور قابل‌توجهی در سلول‌های گروه تحت مواجه نسبت به کنترل افزایش یافت (05/0P<) . در نتیجه، تولید رادیکال‌های آزاد اکسیژن و لیپید پراکسیداسیون و خروج سیتوکروم c از میتوکندری به فراکسیون سیتوزولی درگروه تحت مواجه در مقایسه با گروه کنترل به طور قابل ‌توجهی (05/0p <) کاهش یافت. در مجموع، Fe3O4-CurNPs فعالیت آنتی اکسیدان قوی در سلول‌های فیبروبلاست ایزوله شده از زخم پای دیابتی نشان داد. نتیجه‌گیری: این رویکرد را می‌توان در مطالعات پیش بالینی مورد استفاده قرار داد و ممکن است در آینده در کاهش اثرات زخم‌های دیابتی  اهمیت داشته باشند.  </div> <div style="text-align: justify;">Background & Aims: In the world, every 20 seconds, a patient loses his leg due to diabetes. it is also known that diabetic foot ulcers develop in the feet of about 300,000 patients every year, and it is known that 20,000-30,000 of these patients lose their legs. The increasing prevalence of diabetes worldwide has caused countless personal and social problems. So that today this disease has become an epidemic. Diabetic foot ulcer is a common disease among patients with type 1 and 2 diabetes, which is usually caused by an injury, even if minor, to the feet. The treatment of these wounds in people who do not have diabetes is usually done spontaneously, but in the case of diabetic patients, it is necessary to take care of this wound quickly and pay attention to it to avoid possible risks and problems. Peripheral neuropathy and lower limb ischemia caused by peripheral artery disease are considered to be the main causes of diabetic foot ulcer. Diabetic peripheral neuropathy is one of the accelerating factors in almost 90% of diabetic foot ulcers. This wound is usually formed under the ankle as a result of a break in the skin structure and gradually involves the lower layers of the skin. It is one of the health and economic-social problems. This complication is the main cause of disability and incurs high costs for diabetic patients. Also, infections at the time of diabetic foot ulcer is another problem of sufferers, that's why researchers are trying to use different scientific fields for the best result in improving the damage caused by diabetic foot ulcer. Curcumin, the biologically active substance of turmeric, has wide biological properties, such as anti-inflammatory, antioxidant, anti-diabetic and anti-cancer. Although due to the low solubility of this substance in water, the use of its medicinal and biological properties is limited, but despite its limited availability in the level of biological activity, curcumin has shown positive and noticeable effects in the human digestive system and the body's defense systems. It inhibits various types of diseases. The effective ability of inhibiting the stringing of various proteins in the condition of fibrillation and also inhibiting the production of reactive oxygen species by this molecule have been studied. Curcumin regulates their function by reacting directly or indirectly with more than 30 proteins. The low dissolution of curcumin in water causes its use to be limited. For this reason, many studies have been done to increase its dissolution. Curcumin encapsulation using some carrier molecules, such as bovine serum albumin, increases the effectiveness of curcumin. Betacasein is among the proteins that can create nanostructured micelles that act as a carrier for hydrophobic molecules. In a study, our research group used beta-caseins from camel milk to encapsulate curcumin, the results of which show an increase in the solubility of curcumin up to 2400 times, and to improve the performance of curcumin, today researchers have been able to create nanoparticle structures of this composition. In recent years, studies in the field of nanoparticles are being carried out at a high speed. The scope of nanomedicine includes pharmaceutical applications and nanoelectronic and nanomolecular biosensors. Nanomedicine can have a significant impact on life-threatening diseases. The diseases that can be affected by nanotechnology in the next few years include cancer, diseases of the cardiovascular system, lungs, blood, brain and nerves, diabetes, inflammatory/infectious diseases, and Parkinson's disease or Alzheimer's and orthopedic problems. In recent years, researchers have investigated and scientifically studied various factors such as particle size, nanoparticle morphology, material type selection, and nanomaterial synthesis and optimization techniques to provide an ideal nanosystem for targeted and more effective drug delivery. The diverse properties of nanoparticles have made it possible to provide understandable and reassuring solutions for therapeutic, diagnostic, preventive and biological challenges in the field of nanomedicine research. However, the challenges of the physiological system are very complex and the cells show various responses at the nanoscale level, so understanding the interaction of nanomaterials and biological compounds and nanobiotechnological studies are very necessary and important. Macromolecular synthesis and polymer diversity have found wide applications in therapeutic applications. Nanocomposites and nanoparticles are used in the fields of inducing the growth of cells and also in the delivery of drugs to the target tissue. It has also been shown in cell studies that damage to the cell activates a huge amount of oxidative stress, which has irreparable effects on the systems and organs of living organisms. Methods: We designed superparamagnetic iron oxide nanoparticles loaded with curcumin (Fe3O4 magnetic- CurNPs) to achieve an enhanced co-therapeutic effect. The physicochemical properties of Fe3O4 magnetic- CurNPs were characterized using X-ray diffraction (XRD), and dynamic laser light scattering (DLS) and <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/zeta-potential" title="Learn more about zeta potential from ScienceDirect's AI-generated Topic Pages">zeta potential</a>. Further, to prove Fe3O4 magnetic-CurNPs results in superior therapeutic effects, and also, the cell viability, reactive oxygen species production (ROS), lipid peroxidation level, cytochrome c release, as well as histopathological changes in skin tissue. Results: We showed that effective co-<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/therapeutic-procedure" title="Learn more about treatment from ScienceDirect's AI-generated Topic Pages">treatment</a> with nanoparticle induced <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/oxidative-stress" title="Learn more about oxidative stress from ScienceDirect's AI-generated Topic Pages">oxidative stress</a> and mitochondrial dysfunction in the diabetic foot ulcer. Nanoparticle, as well as cell viability low level reduced in the cells of treated group compared with control (p < 0.05). ROS generation, lipid peroxidation and cytochrome c release were (p < 0.05) increased in the cells of treated group compared with control group. Conclusion: Taken together, Fe3O4 magnetic-CurNPs exhibits potent antioxidant activity in fibroblast isolated from skin diabetic foot ulcer. This approach can be extended to preclinical use in skin foot ulcer treatment in the future.  </div> سلول فیبروبلاست, استرس اکسیداتیو, سمیت سلولی, رادیکال آزاد اکسیژن Fibroblast cell, Stress Oxidative, Cellular toxicity, Reactive Radical Species 1 15 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7634-2&slc_lang=fa&sid=1 Behnaz Ashtari بهناز اشتری 3900319475328460078415 3900319475328460078415 No Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran گروه نانوفناوری پزشکی، دانشکده فناوریهای نوین پزشکی، دانشگاه خدمات درمانی و علوم پزشکی ایران، تهران، ایران Fatemeh ghanbary فاطمه قنبری ghanbary83@yahoo.com 3900319475328460078416 3900319475328460078416 No Department of Chemistry, Mahabad Branch, Mahabad, Iran گروه شیمی، واحد مهاباد، دانشگاه آزاد اسلامی، مهاباد، ایران Parvaneh Naserzadeh پروانه ناصرزاده pnnew2011@yahoo.com 3900319475328460078417 3900319475328460078417 Yes Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran مرکز تحقیقات غدد، انستیتو غدد درون ریز و متابولیسم، دانشگاه علوم پزشکی ایران، تهران، ایران Arash Javad moosavi آرش جواد موسوی 3900319475328460078418 3900319475328460078418 No Shahid Beheshti University of Medical Sciences. Tehran, Iran دانشکده پزشکی دانشگاه علوم پزشکی شهید بهشتی