parisa saberi-hasanabadi
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مقدمه
دیابت شایع ترین بیماری متابولیک ناشی از کمبود نسبی ترشح یا عملکرد انسولین است. دیابت می تواند منجر به عوارض گوناگونی در بدن از جمله آسیب کبدی و کلیوی شود. هدف از این مطالعه، ارزیابی اثرات حفاظتی دی متیل فومارات بر سمیت کبدی و کلیوی موش های دیابتی ناشی از تزریق آلوکسان از مسیرهای التهاب و استرس اکسیداتیو بود.
روش هاموش های ماده از نژاد (C57BL/6) با تزریق داخل صفاقی آلوکسان مونوهیدرات محلول در سرم فیزیولوژی (به میزان 120 میلی گرم به ازای هر کیلوگرم وزن بدن) در 3 روز متوالی دیابتی شدند. موش ها به 7 گروه 5 تایی شامل گروه های دریافت کننده آلوکسان و دی متیل فومارات دسته بندی شدند. موش های دیابتی نوع اول با 3 دوز از دی متیل فومارات (به ترتیب،mg/kg 20، 40 و 80) به مدت 21 روز تحت درمان قرار گرفتند. سپس، آزمون های اختصاصی جهت ارزیابی پارامترهای بیوشیمیایی خون، نشانگرهای استرس اکسیداتیو، بیان ژن های التهابی (TNF-α، IL-6 و NF-kB) و ژن های مرتبط با پیشگیری از تشدید استرس اکسیداتیو و عوارض ناشی از دیابت (شامل بیان دو ژن Sirt-1 (سیرتوئین) و Nrf2) به کمک روش ریل تایم PCR انجام شد. در پایان، مشاهدات هیستوپاتولوژیکی در دو بافت کبد و کلیه موش ها هم ارزیابی گردید.
یافته هاتجویز دی متیل فومارات به موش های دیابتی در یک رفتار وابسته به دوز منجر به کاهش معنادار سطوح گلوکز، AST، ALT و کراتنین خون در مقایسه با گروه شاهد شد. تغییرات هیستوپاتولوژیک کمتر و کاهش بیشتری در سطح شاخص های استرس اکسیداتیو در کلیه و کبد گروه های تیمارشده با دی متیل فومارات در مقایسه با موش های دیابتی مشاهده شد (001/0<P). مواجهه با دی متیل فومارات به شکل معناداری موجب افزایش بیان ژن های Sirt-1 و Nrf2 و کاهش بیان ژن های دخیل در بروز التهاب نسبت به گروه دیابتی در هر دو بافت کبد و کلیه شد.
نتیجه گیریتجویز دی متیل فومارات موجب بهبود شاخص های بیوشیمیایی خون، استرس اکسیداتیو، هیستوپاتولوژی وتعدیل مسیر بیان دو ژن Sirt-1 و Nrf2 در دو بافت کلیه و کبد موش های دیابتی شد.
کلید واژگان: دیابت، آلوکسان، دی متیل فومارات، استرس اکسیداتیو، پاسخ های ضدالتهابی، اثرات حفاظت از بافت کبدی-کلیویBackgroundDespite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field.
MethodsIn this study, type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression, and histopathological changes in the mice kidney and liver.
ResultsThe obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (P< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (P< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group.
ConclusionIn conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways.
Keywords: Diabetes, Alloxan, Dimethyl Fumarate, Oxidative Stress, Anti-Inflammatory Responses, Hepato-Renal-Protective Effects -
سابقه و هدف
پاراکوات ازجمله علف کش های شیمیایی بوده که سمیت بالایی داشته و درصورت مصرف نادرست یا عدم آگاهی در نحوه استفاده باعث مسمومیت کشنده در افراد در معرض این سم، به ویژه فعالان در حوزه کشاورزی می شود. امروزه استفاده از ترکیباتی با منشا طبیعی به منظور بهبود و یا کاهش اثرات مخرب سموم کشاورزی ازمسائل مهمی به شمار می رود که توجه محققان را در این حوزه به خود جلب نموده است. کوئرستین به عنوان فلاونوئیدی طبیعی به مقدار زیاد در میوه ها و سبزیجات یافت می شود. این ترکیب به عنوان نوعی آنتی اکسیدان طبیعی از قدرت زیادی در حذف رادیکال های آزاد برخوردار است. مطالعه حاضر، با هدف ارزیابی اثرات محافظتی کوئرستین بر سمیت تخمدان ناشی از پاراکوآت در موشهای صحرایی، انجام پذیرفت.
مواد و روش هاجهت انجام این پژوهش تجربی، 30 موش بالغ صحرایی نژاد ویستار با میانگین سنی 6 تا 8 ماه و با محدوده وزنی 160 تا 180 گرم به طور تصادفی به 5 گروه آزمایشی شامل 6 عدد موش در هر گروه تقسیم شدند. گروه کنترل مثبت فقط سم پاراکوآت (به میزان 25/1 میلی گرم بر کیلوگرم) و گروه کنترل منفی نرمال سالین دریافت کردند. کوئرستین در دوزهای مختلف (50، 100 و 200 میلی گرم/کیلوگرم) به صورت داخل صفاقی به حیوانات دچار سمیت حاد تزریق شد. بعد از 24 ساعت، حیوانات قربانی شده و تخمدان آن ها بیرون آورده شد. پس از شستشو، مراحل تعیین شاخص های استرس اکسیداتیو در گروه ها صورت گرفت.
یافته هاموش های تحت تیمار با تمامی غلظت های کوئرستین شامل 50 (0/01<p)، 100 (0/001<p) و 200 میلی گرم بر کیلوگرم (0/0001<p) اختلاف معنی داری در مقایسه با گروه کنترل مثبت داشتند. با افزایش غلظت کوئرستین، بهبود عملکرد مهار سمیت پاراکوات در این دسته از حیوانات مشاهده گردید. نتایج نشان داد که غلظت های مختلف کوئرستین توانایی مهار واکنش پراکسیداسیون لیپیدی ناشی از سمیت پاراکوات را داشته و گروه کنترل مثبت از لحاظ آماری در مقایسه با گروه کنترل منفی دارای اختلاف معنی دار بود (0/001<P). با تجویز کوئرستین در غلظت های مختلف، کاهش تولید لیپید پراکسیداسیون مشاهده شد. از لحاظ آماری، کوئرستین در غلظت (mg/kg) 50 دارای اختلاف معنی داری با گروه کنترل مثبت بود (0/01<P) و در غلظت های (mg/kg) 100 و 200 نیز این اختلاف معنی داری مشهود بود (0/0001<P). در غلظت 200 میلی گرم برکیلوگرم از کوئرستین، بیش ترین اثرگذاری در کاهش تولید لیپید پراکسیداسیون مشاهده گردید.
استنتاجنتایج به دست آمده از پژوهش حاضر نشان داد که کوئرستین می تواند به عنوان ترکیبی موثر و آنتی اکسیدانی مفید در بهبود شاخص های استرس اکسیداتیو و بافت تخمدان موش مفید واقع شود. کوئرستین به صورت وابسته به دوز می تواند آسیب اکسیداتیو ناشی از پاراکوآت را در بافت های تخمدان موش کاهش دهد. کوئرستین به طور بالقوه می تواند جهت کنترل سمیت تخمدان، تعدیل و یا مهار عوامل اکسیداتیو، تقویت سیستم ایمنی و تقویت سیستم آنتی اکسیدانی در مدل های حیوانی استفاده شود. احتمالا می توان از آن به عنوان نوعی مکمل بی خطر در ترکیب با سایر داروهای تاثیرگذار بر سیستم ایمنی استفاده کرد. با این حال، این فرضیه همراه با اثر سایر تداخلات دارویی باید با استفاده از مطالعات in vivo مناسبی تایید شود. درک فرآیند مرگ سلولی ناشی از پاراکوآت و اثر مهارکنندگی آنتی اکسیدان های طبیعی بر آن، نقشه راه جدیدی را برای مطالعات آتی به منظور توسعه استراتژی های درمانی جدید ارائه می کند.
کلید واژگان: پاراکوآت، کوئرستین، سمیت، تخمدان، شاخص های استرس اکسیداتیوBackground and purposeParaquat is one of the chemical herbicides with high toxicity. In case of incorrect consumption, this chemical causes fatal poisoning in people, especially those active in the field of agriculture. Nowadays, using compounds of natural origin to improve or reduce the harmful effects of agricultural pesticides is one of the important issues that has attracted the attention of researchers in this field. Quercetin as a natural flavonoid is found in large quantities in fruits and vegetables. As a kind of natural antioxidant, this compound has great power in removing free radicals. The purpose of this research was to evaluate the protective effects of quercetin on ovarian toxicity caused by paraquat in rats.
Materials and methodsTo conduct this experimental research, 30 adult Wistar rats with an average age of 6 to 8 months and a weight range of 160 to 180 gr were randomly divided into 5 experimental groups including 6 rats in each group. Paraquat (1.25 mg/kg, intraperitoneally) was injected into mice. Then quercetin was injected intraperitoneally in concentrations of 50, 100, and 200 mg/kg. The negative control group received only normal saline. After 24 hours, the animals were sacrificed and their ovaries were evaluated for changes in oxidative stress indices.
ResultsThe results showed that paraquat significantly increased the reactive oxygen species (ROS), protein carbonyl, and lipid peroxidation, and significantly decreased glutathione content and survival of ovarian tissue cells when compared with the control group (P<0.001). The results showed that different concentrations of quercetin could inhibit the lipid peroxidation reaction caused by paraquat toxicity, and the positive control group had a statistically significant difference compared to the negative control group (P<0.001). By administering quercetin in different concentrations, we saw a decrease in the production of lipid peroxidation. From a statistical point of view, quercetin at the concentration (mg/kg) of 50 had a significant difference with the positive control group (P<0.01) and this significant difference was also evident at the concentrations of (mg/kg) 100 and 200 (P<0.0001). Increasing the concentration of quercetin was associated with improved performance in inhibiting paraquat toxicity.
ConclusionResults showed that quercetin can be useful as an effective antioxidant combination in improving oxidative stress indicators and ovarian tissue of mice. Quercetin can reduce paraquat-induced oxidative damage in rat ovarian tissues in a dose-dependent manner. Quercetin can potentially be used to control ovarian toxicity, modulate or inhibit oxidative factors, strengthen the immune system, and strengthen the antioxidant system in animal models. Probably, it can be used as a kind of safe supplement in combination with other drugs affecting the immune system. However, this hypothesis along with the effect of other drug interactions should be confirmed using appropriate in vivo studies. Understanding the process of cell death caused by paraquat and the inhibitory effect of natural antioxidants on it provides a new road map for future studies to develop new therapeutic strategies.
Keywords: Paraquat, Quercetin, Toxicity, Ovary, Oxidative Stress Indexes -
During the COVID-19 pandemic, there has been a resurgence of mucormycosis, a rare and opportunistic fungal infection, with India reporting a particularly notable increase in incidence. Mucormycosis is a life-threatening condition that requires prompt diagnosis and treatment to prevent high mortality rates and severe sequelae. It is caused by the inhalation of spores from ubiquitous filamentous fungi belonging to the order Mucorales. Individuals with compromised immune systems or underlying conditions, such as diabetes, ketoacidosis, and neutropenia, are particularly vulnerable to infection. The risk and severity of mucormycosis are exacerbated by several factors, including corticosteroid therapy, prolonged intensive care stay, and the use of ventilators. Additionally, contaminated oxygen humidifiers pose a significant risk. Effective management of mucormycosis in critically ill COVID-19 patients relies on early diagnosis, optimization of predisposing factors, timely antifungal treatment, surgical debridement, and adjuvant therapies. Imaging modalities such as contrast-enhanced CT scans and MRI are crucial for guiding surgical debridement and assessing disease extent. This review article provides a comprehensive overview of the clinical pathogenesis, risk factors, diagnosis, treatment, and challenges associated with mucormycosis in COVID-19 patients, summarizing the latest findings in this field.
Keywords: COVID-19 Infections, Mucormycetes, Organ Damage, Risk Factors, Linkages -
سابقه و هدف
مایکوتوکسینها متابولیت ثانویه قارچها هستند و دارای اثر سرطانزایی میباشند. اکراتوکسین(A) یکی از مایکوتوکسینهایی است که باعث آلودگی گندم و آرد حاصل از آن بسته به شرایط مختلف تولید، نگهداری و ذخیره میگردد. با توجه به سرطانزایی و جهشزا بودن این سم، پایش آلودگی آرد گندم مصرفی در نانواییها و جلوگیری از ورود این محصول به زنجیره تامین نان، امری ضروری است. هدف از این مطالعه شناسایی و تعیین مقدار اکراتوکسین(A) در آرد گندم مصرفی نانواییهای شهر ساری در سال 1396 با استفاده از دستگاه کروماتوگرافی مایع با کارایی بالا (HPLC) بود.
مواد و روش هادر این مطالعه تجربی، 30 نمونه از آرد مورد استفاده در تهیه نانهای لواش، بربری و سنگک از 5 منطقه جغرافیایی در سطح شهر ساری (استان مازندران) و در تابستان سال 1396، جمعآوری و غلظت اکراتوکسین(A) موجود در آنها با استفاده از HPLC از طریق خالصسازی با ستون ایمونوافینیتی تعیین گردید.
یافته هانتایج نشان داد که در هیچیک از مجموع 30 نمونه آرد برداشت شده، آلودگی به اکراتوکسین(A) مشاهده نشد. یافتههای حاصل، در انطباق با غلظت قابل قبول ذکرشده از اکراتوکسین(A) در استاندارد ملی ایران بود.
استنتاجبا توجه به حجم بسیار زیاد نان مصرفی در سطح جامعه و با تکیه بر نتایج حاصل از این مطالعه، آرد مورد استفاده در تهیه نان در نانواییهای مورد بررسی به عنوان ماده اولیه ایمن از نظر میزان اکراتوکسین(A) مطابق با حدود مجاز تعیین شده توسط استاندارد ملی ایران بوده و قابل قبول برای مصرف است.
کلید واژگان: اکراتوکسین(A)، آرد گندم، نان، کروماتوگرافی مایع با کارآیی بالاBackground and
purposeMycotoxins are secondary metabolites of fungi that have carcinogenic effects. Ochratoxin A (OTA) is a highly toxic mycotoxin that can contaminate wheat grains and flour under various conditions of production, storage, and maintenance. Considering the carcinogenicity and mutagenicity of this toxin, it is necessary to monitor the contamination of wheat flour used in bakeries and to prevent this product from entering the bread supply chain. The aim of this study was to identify and determine the amount of OTA in wheat flour consumed by bakeries in Sari, during 2017 using high performance liquid chromatography (HPLC) method.
Materials and methodsIn this study, 30 samples of flour used in the preparation of lavash, barbari and sengak bread were collected from five different geographical areas of Sari (Mazandaran province) in 2017. The concentration of OTA was finally determined using HPLC device and through purification with an immunoaffinity column.
ResultsNo concentration of OTA was observed in any of the tested samples. The results were in compliance with the mentioned reference values of OTA concentration in bakery products based on the Iranian National Standard Organization.
ConclusionBased on the results, the flour used in breads is safe in terms of OTA. This amount is in accordance with the permissible limits set by the Iranian National Standard Organization and is acceptable for consumption.
Keywords: Ochratoxin A (OTA), wheat flour, bread, high performance liquid chromatography (HPLC) -
Background
Extensive application of zinc oxide nanoparticles has increased the likelihood of its release into the environment and subsequent human exposure and toxicity. The toxicity is thought to be a combined effect of intracellular particles and the release of dissolved zinc ions.
ObjectivesThis review outlines the possible mechanisms of zinc oxide toxicity in biological organs through in vitro and in vivo experiments.
MethodsWe reviewed articles published between 2001 and 2021. In this way, we did a manual search of Google Scholar and scientific databases, including PubMed, Web of Science, Scopus, and Embase, with keywords such as “zinc oxide nanoparticles”, “toxicity mechanism”, and “in vivo and in vitro studies”. The other qualified papers contained the history of identifying zinc oxide nanoparticles, the toxicity of metallic nanoparticles, and physical, chemical, and biological side effects with topical and systematic approaches.
ResultsThe main mechanism suggested for zinc-based nanoparticles-induced cell damage is via the induction of increased levels of reactive oxygen species, which are oxidative stress markers. This mechanism has also been found to be a key mechanism for the cytotoxicity of other metal nanomaterials. Zinc-based nanoparticles were found to induce oxidative DNA damage, inflammation, progressive degenerative cell changes, cell cycle arrest, cytogenetic alterations, and ROS-triggered mitochondria-mediated apoptosis in human organs.
ConclusionThis review sheds light on the full understanding of in vitro and in vivo toxicity assessment of zinc oxide nanoparticles, highlighting the health concerns from the perspective of ZnO nanoparticles release to the ecosystem after their increasing application.
Keywords: Zinc oxide, Nanoparticles, Toxicity, Oxidative stress -
The coronavirus disease (COVID)-19 pandemic led to a new challenge in the field of effective treatment methods for this disease. Antiviral and immunomodulatory agents were suggested as potential therapeutic methods in this field. Since the most severe clinical symptoms associated with COVID-19 disease appear to be acute respiratory syndrome, azithromycin has been proposed as a potentially effective drug in this context. We have updated the evidence and selected all relevant items to understand the mechanism of role of azithromycin, clinical efficacy, and their side effects in coronavirus disease-19 treatment on July 20th and updated on March 20th, 2020. A literature search of electronic databases including the Web of Science, PubMed, and Google Scholar was conducted by searching keywords such as "Azithromycin", "COVID-19", and "Combination therapy". The ultimate goal of this review was identifying eligible studies about the pharmacological activities, safety, and effectiveness of azithromycin in treating COVID-19 patients. Immunomodulatory properties of azithromycin include the ability to reduce cytokine production, maintain epithelial cell integrity, or prevent lung fibrosis. The use of azithromycin in some studies was associated with a decrease in mortality and need for ventilation in patients. These properties can be useful during the period of COVID-19 infection, especially in patients with underlying diseases. However, the evidence for the use of azithromycin is still scarce and the quality of the studies is low. In some retrospective studies, azithromycin was mainly evaluated in combination with hydroxychloroquine, which showed no particular advantage. The results of this review showed that azithromycin has appropriate and well-known safety characteristics in the treatment of patients with COVID-19. However, the most appropriate dosage in different stages of the disease and the effect of its combination with other drugs are important questions that should be considered in future clinical trials.
Keywords: Azithromycin, COVID-19, Clinical trial, Antiviral, immunomodulatory agents, Cytokine release syndrome -
Background
Amygdalin has a wide range of pharmacological activities including analgesic and anti-asthmatic effects. In spite of several studies that have shown the cytotoxic effects of amygdalin on the different cancer cell lines, no general agreement has yet been reached on the anti-cancer aspect of amygdalin.
ObjectivesThe review aims to focus on the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation.
MethodsElectronic databases including the Web of Science, PubMed, Google Scholar and sciencedirect were searched up to identify eligible studies about of the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation. Generally, a total of 90 papers about in vitro/in vivo studies on amygdalin have been reviewed.
ResultsPharmacological activities of amygdalin have been well documented over the years, however, in some cases; dose-dependent toxicity has been reported in the human body. Since the acute toxicity experiments of amygdalin has proved that the toxicity of oral administration route is far greater than the intravenous route. Thus, several in vitro and in vivo studies are needed to assess the amygdalin’s pharmacological value as the induction of apoptosis and anti-cancer drug.
ConclusionAmygdalin is known to have generally dose-dependent effects with positive or desirable effects at lower doses and undesirable effects generally above this level of intake in some in the treatment of some diseases, although there is substantial inter-individual variation.
Keywords: Amygdalin, Pharmacological activity, Toxicology, Review -
Background
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To increase the success in treating patients with COVID-19, many drug suggestions and some clinical studies are shared in the literature. However, the combination of several drugs with other clinical care has improved patients' conditions. And this review discusses some side effects of Covid-19 drugs' adverse effects.
ObjectivesHere, we have shortly reported the recent updates on the most common and plausible drugs for treating COVID-19 patients. We also compare these treatment options based on their impact on symptom management, inpatient length of stay, and overall morbidity and mortality.
MethodsAn extensive literature search was performed through PubMed, Scopus, Web of Science, and Google Scholar. Most of the keywords used were: "COVID-19", "Side effects of used drugs," "Treatment of COVID-19", "Risk factors," "Organ damage," and "Methods of diagnosis and treatment."
ResultsAnti-inflammatory, antimicrobial, and vitamin supplements do not have obvious benefits, but there is limited information to consider. Other factors and drugs such as improved plasma, eculizumab, immunoglobulins, IgG1-neutralizing monoclonal antibodies, remidseiver, steroids, and tosilizumab have shown potential effects on patient's length of hospital stay and mortality. Currently, there is no evidence that any other vaccines, apart from those specifically designed for the SARS-Cov-2 virus, will protect against COVID-19.
ConclusionSince the prevention of the COVID-19 virus is a new issue in the medical world, there is no known effective treatment option in this area, and the prevention of its adverse side effects has not been conclusively proven. Of course, the occurrence of side effects in patients undergoing treatment such as hepatotoxicity, retinal damage, nephrotoxicity, and cardiotoxicity proves that the necessary caution should be used in drug combination methods.
Keywords: COVID-19, Medicines, Toxicity, Convalescent plasma, Nanotherapeutics, Clinical observations, Side effects -
Background
Coronavirus Disease 2019 (COVID-19) is an ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2). The outbreak was first identified in Wuhan, China, in December 2019.
ObjectivesThis review gives a bird’s-eye view of the COVID-19 pandemic and its various effects on human society. Since knowledge about this virus is rapidly evolving, readers are urged to update themselves regularly.
MethodsIn this review, our searching was performed on international databases of Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) from October 2019 to June 2020.
ResultsMost patients infected with COVID‑19 have mild symptoms. Approximately 15% of patients have severe pneumonia, and about 5% acute distress syndrome or organ failure. In the absence of definitive treatment and vaccines, the most effective measure is to prevent infection, particularly in those at high risk of taking the severe form of the disease with adverse outcomes. Pharmacotherapy is essentially supportive; the role of antiviral agents is yet to be established. The commonest drugs used in treating this viral disease are tocilizumab, remdesivir, favipiravir, and camostat mesilate. Also, drugs related to malaria, AIDS, and Ebola, such as hydroxychloroquine, are widely used. Based on physical examinations alone, it is impossible to comment with certainty in mild cases of the disease. Accordingly, a wide range of methods is used for diagnosing and treating the disease. Various variables in reducing the severity of the epidemic and the effects of the virus require special management at the national, regional, and global levels.
ConclusionThis review summarizes the latest findings in safety, management, and public services related to the COVID-19 virus epidemic.
Keywords: COVID-19 Pharmacotherapy, Prevalence, Diagnosis, Managemen -
Although ZnO nanoparticles possess novel properties that make them available to a wide range of applications, the questions regarding their safety may arise when they come in direct contact with biological systems (such as skin, lungs, and tissues). In this study, we evaluated the possible toxic effects of different dosages of zinc oxide nanoparticles (25, 50 and 100 mg/kg) in three treatment groups in four weeks on skin and muscle tissues of treated rats. For toxicological assessments, male rats weighing 150 to 200 g were exposed to three different concentrations of zinc oxide nanoparticles (25 , 50 and 100mg/kg) in an acute study.Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with the negative control group. All changes were compared with the negative control group and the results were analyzed by one-way analysis of variance (ANOVA). Results have been indicated that the mean levels of the histopatological injuries were scored in experimental groups and showed no significant difference with control group that mean,the number of vacuole degeneration showed significant increase in high dose group (p<0.05). The results showed that the topical application of zinc oxide can not make remarkable effects on the skin and skeletal muscle tissue of the rats in low and medium doses. Although, we did not find any harmful effects on the use of low and medium dosages of zinc oxide nanoparticles on the skin and musculoskeletal system, we can not ignore the observations regarding the sensitivity of cells and tissues to the potential cytotoxic effects this kind of nanoparticles. Therefore, it is suggested to conduct further researches on the complex toxicity mechanism of zinc oxide nanoparticles in living organisms.Keywords: Zinc Oxide Nanoparticles, Toxicity, Rats, Skin, tissues histopathology
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