Iranian Journal of Pharmaceutical Research最新文献

{"title":"Sub-chronic Toxicity Study of Heracleumlasiopetalum Extract Towards Healthy Sprague Dawley Rats","authors":"Enas Sabah Hassan, Heshu Rahman, Shirwan Hamasalih Omer","doi":"10.5812/ijpr-144209","DOIUrl":"https://doi.org/10.5812/ijpr-144209","url":null,"abstract":"Background: Heracleum species are commonly used as spices, flavorings, and food additives. Members of the genus Heracleum offer many medicinal benefits but may also pose adverse effects on human health. Objectives: To prepare a crude leaf extract of Heracleumlasiopetalum and assess its toxicity profile towards healthy rats. Methods: The H. lasiopetalum leaf extract was prepared using pure methanol and ethyl acetate (1:10) at room temperature over a period of 72 hours. After filtration, the crude extract was obtained using a rotary evaporator at 40 - 45°C. Subsequently, various doses of the H. lasiopetalum extract were administered orally to healthy Sprague Dawley rats at three doses (300, 600, and 900 mg/kg body weight) for four weeks to test for toxicity. Blood samples were examined for hematologic and biochemical changes, while the liver, kidneys, and heart were examined for histopathological changes. Results: The toxicity study revealed no mortality at low and medium doses, as well as no clinical toxicity indicators. Additionally, there were no significant alterations observed in the haematological, biochemical, and histopathological profiles of the treated animals throughout the 28-day experiment. However, at high doses, the mortality rate was significantly elevated, accompanied by notable histopathological changes. Conclusions: Continuous administration of high doses of H. lasiopetaum may induce potential toxic effects in the treated animals.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial.","authors":"Baran Roshan N S, Bahador Mirrahimi, Farhad Najmeddin, Seyedeh Narjes Ahmadizadeh, Azita Behzad, Seyedeh Masumeh Hashemi, Maryam Alemzadeh, Niloufar Taherpour","doi":"10.5812/ijpr-145933","DOIUrl":"10.5812/ijpr-145933","url":null,"abstract":"<p><strong>Background: </strong>Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC₂₄/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have showed that intermittent infusion of vancomycin (IIV) may not achieve the desired levels, continous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity.</p><p><strong>Objectives: </strong>This study aimed to compare the serum concentrations, AUC₂₄, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population.</p><p><strong>Methods: </strong>This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC₂₄ between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated.</p><p><strong>Results: </strong>Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC₂₄ ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC₂₄ (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups.</p><p><strong>Conclusions: </strong>This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted LC/HRMS Metabolomics Analysis and Anticancer Activity Assay on MCF-7 and A549 Cells from Coleus amboinicus Lour Leaf Extract","authors":"K. Gurning, S. Suratno, Endang Astuti, W. Haryadi","doi":"10.5812/ijpr-143494","DOIUrl":"https://doi.org/10.5812/ijpr-143494","url":null,"abstract":"Background: Cancer remains the leading cause of death globally, with breast cancer being the foremost cause among women and lung cancer ranking second for both women and men. Objectives: This study aimed to identify the metabolomic content of Coleus amboinicus leaves and evaluate their anticancer activities against breast and lung cancer cells, thereby providing insights into potential alternative treatments for these cancers and initiating research on active isolates from C. amboinicus leaves. Methods: The research methodology involved maceration using ethanol, followed by multistage partitioning with solvents n-hexane, chloroform, and ethyl acetate. Phytochemical screening was performed using standard reagents to detect the presence of alkaloids, phenolics, polyphenols, flavonoids, steroids/triterpenoids, and saponins. Metabolomic profiling was conducted using LC/HRMS, and the anticancer activities against lung cancer cells (A549) and breast cancer cells (MCF-7) were assessed using the MTT assay. Results: The results showed that the C. amboinicus extract contains various secondary metabolite groups such as alkaloids, phenolics and polyphenols, flavonoids, steroids, triterpenoids, and saponins. Conclusions: The diverse metabolomic profile of the C. amboinicus leaf extract demonstrated potential activity against cancer, as evidenced by in vitro tests on lung (A549) and breast (MCF-7) cancer cells. C. amboinicus leaf extract shows promise as an active ingredient in the prevention and alternative natural treatment of lung and breast cancer. Further research and testing, both in vivo and clinically, are warranted.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140681211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of the Synthesis and Radiolabeling of ZIF-8 Nanoparticles","authors":"Mahnaz Ahmadi, Elham Asadian, Mona Mosayebnia, S. Dadashzadeh, S. Shahhosseini, Fateme Ghorbani Bikorpeh","doi":"10.5812/ijpr-144928","DOIUrl":"https://doi.org/10.5812/ijpr-144928","url":null,"abstract":"Background: Lately, there has been increasing interest in the benefits of metal-organic frameworks, and among them, zeolitic imidazolate frameworks (ZIF - 8) stand out as one of the most commonly employed systems owing to their unique characteristics. Objectives: Given that properties like particle size play a key role in biomedical applications of nanoparticles, optimizing the synthesis conditions becomes crucial. Additionally, it is essential to label these nanoparticles to track them effectively within the body. Methods: Zeolitic imidazolate frameworks nanoparticles were synthesized under various conditions, including high and room temperature, using two different solvents: Water and methanol. Modifications were made to the reaction temperature and the ratio of reactants to improve the outcomes. Particle size and size distribution were assessed in all conditions. Additionally, the radiolabeling of nanoparticles was examined using four different methods to identify the method with the highest efficiency and radiochemical purity. Results: The optimum conditions for ZIF-8 synthesis were determined at 50°C using methanol as the solvent. A reactant weight ratio of 1 : 2 (zinc nitrate to 2 - methylimidazole) was utilized. The most effective radiolabeling approach involved using tin chloride as a reducing agent, with the reaction mixture maintained at a temperature of 70°C for 30 minutes. Conclusions: In this study, the optimum conditions were successfully identified for synthesizing and labeling ZIF-8 nanoparticles. These nanoparticles have the potential to serve as effective carriers for diagnostic and therapeutic agents.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-clinical Safety Evaluation of Camelina Oil: Acute and 12-Week Oral Toxicities","authors":"Kambiz Varmira, D. Kahrizi, Azarm Sanjari, Khodabakhsh Rashidi, Leila Hosseinzadeh, N. Amin, Fereshteh Jalilian","doi":"10.5812/ijpr-140666","DOIUrl":"https://doi.org/10.5812/ijpr-140666","url":null,"abstract":": This study assessed the acute and sub-chronic toxicity of Camelina oil, a well-known oil rich in polyunsaturated fatty acids that enhance cellular immunity and human health, in Wistar rats. Wistar rats, 5 per sex per group, were randomly assigned to three groups for acute (14 days) toxicity studies and five groups for sub-chronic (90 days) toxicity studies. In the acute study, Camelina sativa oil was administered orally at a single dose of 5000 mg/kg of body weight (BW). The positive control group received a single dose of 5 000 mg/kg BW Canola oil by gavage. In the sub-chronic study, Groups III-V received 250, 500, and 1 000 mg/kg BW of Camelina oil, while Groups I and II received ultra-pure water and Canola oil at a dose of 500 mg/kg BW, respectively. Throughout the experiment, clinical signs, mortality, and body weight were monitored. At the end of the sub-chronic study, hematological, biochemical, and histopathological investigations were conducted. Administration of Camelina oil and Canola had no significant effect on daily weight gain (P > 0.05) of the test rats. Serum calcium levels decreased while phosphorous levels increased in male rats treated with Camelina oil. Other hematological and biochemical parameters showed no significant differences or dose-response effects between control and seed oil groups in both sexes (P < 0.05). Moreover, in animal necropsy, there were no apparent lesions in the liver, heart, and kidney organs in any of the doses administered. In conclusion, the results suggest that oral administration of Camelina oil is unlikely to be toxic. Therefore, the possibility for the development of future human nutrition should be considered.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140729896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Molecular Landscape of Endometriosis: A Bioinformatics Approach to Uncover Signaling Pathways and Hub Genes","authors":"Junhua Tian, Xiaochun Liu","doi":"10.5812/ijpr-144266","DOIUrl":"https://doi.org/10.5812/ijpr-144266","url":null,"abstract":"Background: Endometriosis is a chronic gynecological disorder characterized by the ectopic growth of endometrial tissue outside the uterus, leading to debilitating pain and infertility in affected women. Despite its prevalence and clinical significance, the molecular mechanisms underlying the progression of endometriosis remain poorly understood. This study employs bioinformatics tools and molecular docking simulations to unravel the intricate genetic and molecular networks associated with endometriosis progression. Objectives: The primary objectives of this research are to identify differentially expressed genes (DEGs) linked to endometriosis, elucidate associated biological pathways using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), construct a Protein-Protein Interaction (PPI) network to identify hub genes, and perform molecular docking simulations to explore potential ligand-protein interactions associated with endometriosis. Methods: Microarray data from Homo sapiens, specifically Accession: GDS3092 Series = GSE5108 (Platform: GPL2895), were retrieved from the NCBI Gene Expression Omnibus (GEO). The data underwent rigorous preprocessing and DEG analysis using NCBI GEO2. Database for Annotation, Visualization, and Integrated Discovery analysis was employed for functional annotation, and a PPI network was constructed using the STITCH database and Cytoscape 3.8.2. Molecular docking simulations against target proteins associated with endometriosis were conducted using MVD 7.0. Results: A total of 1 911 unique elements were identified as DEGs associated with endometriosis from the microarray data. Database for Annotation, Visualization, and Integrated Discovery analysis revealed pathways and biological characteristics positively and negatively correlated with endometriosis. Hub genes, including BCL2, CCNA2, CDK7, EGF, GAS6, MAP3K7, and TAB2, were identified through PPI network analysis. Molecular docking simulations highlighted potential ligands, such as Quercetin-3-o-galactopyranoside and Kushenol E, exhibiting favorable interactions with target proteins associated with endometriosis. Conclusions: This study provides insights into the molecular signatures, pathways, and hub genes associated with endometriosis. Utilizing DAVID in this study clarifies biological pathways associated with endometriosis, revealing insights into intricate genetic networks. Molecular docking simulations identified ligands for further exploration in therapeutic interventions. The consistent efficacy of these ligands across diverse targets suggests broad-spectrum effectiveness, encouraging further exploration for potential therapeutic interventions. The study contributes to a deeper understanding of endometriosis pathogenesis, paving the way for targeted therapies and precision medicine approaches to improve patient outcomes. These findings advance our understanding of the molecular mechanisms in endometriosis (EMS), offering promising av","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140733875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Transplantation Alleviates Doxorubicin-Induced Toxicity in Rat Renal Cells.","authors":"Enayatollah Seydi, Mahsa Andalib, Sana Yaghoubi, Amir Fakhri, Jale Yuzugulen, Abdollah Arjmand, Jalal Pourahmad","doi":"10.5812/ijpr-146033","DOIUrl":"10.5812/ijpr-146033","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is used in the treatment of various cancers and has good effectiveness. However, its therapeutic use is limited due to its effects on various organs and healthy cells. Doxorubicin can affect the kidneys and cause toxicity. Evidence shows that DOX induces nephrotoxicity through oxidative stress.</p><p><strong>Objectives: </strong>In this research, we examined the effect of mitochondrial transplantation on improving mitochondrial and cellular toxicity caused by DOX on renal proximal tubular cells (RPTCs).</p><p><strong>Methods: </strong>The research measured 7 toxicity parameters, including cell lysis, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) decline, GSH and GSSG content, lipid peroxidation (LPO), adenosine triphosphate (ATP) content, and Caspase-3 activity (the final mediator of apoptosis). Active fresh mitochondria were prepared from Wistar rat kidney.</p><p><strong>Results: </strong>The findings indicated that DOX caused cytotoxicity in RPTCs. Additionally, DOX induced oxidative stress by increasing the level of reactive oxygen species, reducing glutathione content, and elevating lipid peroxidation. Moreover, it led to damage to the mitochondrial membrane, increased caspase-3 activity, and decreased ATP content. Mitochondrial transplantation, as a new therapeutic approach, reduced oxidative stress, mitochondrial membrane damage, and apoptosis caused by DOX in RPTCs. Furthermore, this therapeutic approach increased the ATP content in RPTCs.</p><p><strong>Conclusions: </strong>Our study suggests that this therapeutic approach could be helpful in the treatment of drug-induced nephrotoxicity.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal-On Fluorescence Biosensor for Detection of miRNA-21 Based on ROX labeled Specific Stem-Loop Probe.","authors":"Somayeh Heidarian, Laya Takbiri Osgoei, Shohreh Zare Karizi, Jafar Amani, Sedigheh Arbabian","doi":"10.5812/ijpr-144368","DOIUrl":"10.5812/ijpr-144368","url":null,"abstract":"<p><strong>Background: </strong>The abnormal expression of microRNA (miRNA) influences RNA transcription and protein translation, leading to tumor progression and metastasis. Today, reliably identifying aberrant miRNA expression remains challenging, especially when employing quick, simple, and portable detection methods.</p><p><strong>Objectives: </strong>This study aimed to diagnose and detect the miR-21 biomarker with high sensitivity and specificity.</p><p><strong>Methods: </strong>Our detection approach involves immobilizing ROX dye-labeled single-stranded DNA probes (ROX-labeled ssDNA) onto MWCNTs to detect target miRNA-21. Initially, adsorbing ROX-labeled ssDNA onto MWCNTs causes fluorescence quenching of ROX. Subsequently, introducing its complementary DNA (cDNA) forms double-stranded DNA (dsDNA), which results in the desorption and release from MWCNTs, thus restoring ROX fluorescence.</p><p><strong>Results: </strong>The study examined changes in fluorescence intensities before and after hybridization with miRNA-21. The fluorescence emission intensities responded linearly to increases in miR-21 concentration from 10^-9 to 3.2 × 10^-6 M. The developed fluorescence sensor exhibited a detection limit of 1.12 × 10^-9 M.</p><p><strong>Conclusions: </strong>This work demonstrates that using a nano-biosensor based on carbon nanotubes offers a highly sensitive method for the early detection of colorectal cancer (CRC), supplementing existing techniques.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Ex-Vivo Skin Permeation of Sildenafil Citrate Microemulsion System for Transdermal Delivery.","authors":"Nasibeh Jamali, Eskandar Moghimipour, Fatemeh Nikpour, Anayatollah Salimi","doi":"10.5812/ijpr-139381","DOIUrl":"10.5812/ijpr-139381","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a microemulsion (ME)-based skin delivery platform containing sildenafil citrate (SC)-ME and evaluate its in vitro skin permeability.</p><p><strong>Methods: </strong>Accurate MEs were prepared using pseudo-ternary phase diagrams and a full factorial design with three variables at two levels. After the design phase, suitable ratios of oil, water, and a mixture of surfactant (S) and cosurfactant (CS) were selected to prepare various SC-ME formulations. These SC-MEs were analyzed for stability, droplet size, in vitro SC release, skin permeability, and viscosity properties.</p><p><strong>Results: </strong>The droplet size of the ME samples ranged from 6.24 to 32.65 nm, with viscosities between 114 to 239 cps. Release profiles indicated that 26 to 60% of SC was released from the different SC-MEs within 24 hours. All ME formulations significantly enhanced the permeability coefficient (P) through rat skin. Specifically, the flux (J_ss) in SC-ME7 increased by approximately 117 times (J_ss = 0.0235 mg/cm².h) compared to the control sample (0.0002 mg/cm².h).</p><p><strong>Conclusions: </strong>The study concluded that the proportions of the water or oil phase and the S/CS mixture in the MEs significantly influenced the physicochemical characteristics and permeation parameters. The selected MEs improved both the permeability coefficient and the rate of permeation through rat skin. The enhanced drug delivery through and into deep skin layers is a key attribute of an ideal dermal ME. These findings suggest that MEs could serve as effective transdermal delivery systems for SC and similar drugs. However, in vivo assays and clinical research are needed to confirm the therapeutic efficacy of MEs.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal Fibrosis and Oxidative Stress Induced by Silica Nanoparticles in Male Rats and Its Molecular Mechanisms","authors":"Bakhta Aouey, Khadija Boukholda, A. Ciobica, Vasile Burlui, Rachid Soulimani, Fatiha Chigr, Hmadi Fetoui","doi":"10.5812/ijpr-143703","DOIUrl":"https://doi.org/10.5812/ijpr-143703","url":null,"abstract":"Background: The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown. Objectives: This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity. Methods: Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers. Results: The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated. Conclusions: This study provided a new research clue for the role of ROS and deregulated TGF-β signaling pathway in SiNPs nephrotoxicity.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140379619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}