Amin Hassanshahi, Ayat Kaeedi, Mohammad Reza Rahmani, J. Hassanshahi
{"title":"The Effects of ThymusCaramanicus Jalas Extract and Its Main Constituent Carvacrol Against Cisplatin-Induced Nephrotoxicity in Mice","authors":"Amin Hassanshahi, Ayat Kaeedi, Mohammad Reza Rahmani, J. Hassanshahi","doi":"10.5812/ijpr-140212","DOIUrl":"https://doi.org/10.5812/ijpr-140212","url":null,"abstract":"Background: Cisplatin, an anti-cancer chemotherapy drug, has nephrotoxic effects. Thymus caramanicus Jalas (TCJ) has antioxidant effects due to its main components. Objectives: In the current research, we assessed the impact of TCJ extract and its main compound on cisplatin-induced nephrotoxicity in mice. Methods: Forty-two male mice were used in the study. Depending on their group, the animals received saline, carvacrol (10 mg/kg), or TCJ extract (50, 100, and 150 mg/kg) for 10 days. On the fifth day, mice received cisplatin (7.5 mg/kg, i.p.). After 10 days, serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. Additionally, malondialdehyde (MDA) and glutathione (GSH) contents, as well as the activity levels of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the kidney tissues. The western blotting method was used to determine the kidney's expression of cleaved caspase-3, Bax, Bcl-2, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TNF-α). Kidney tissue damage score (KTDS) was assessed using the hematoxylin-eosin (H&E) staining method. Results: Cisplatin significantly increased serum Cr, KTDS, MDA, BUN levels, NF-κB, TNF-α, cleaved caspase-3, and Bax protein expression in the cisplatin group compared to the control group (P < 0.01). Additionally, cisplatin significantly decreased the kidney tissue's TAC and GSH content, activity levels of SOD, catalase, and GPx indicators, and expression of Bcl-2 protein (P < 0.05). TCJ and carvacrol significantly ameliorated these indicators in the cisplatin + TCJ (150 mg/kg) and cisplatin + carvacrol (10 mg/kg) groups compared to the cisplatin group (P < 0.05). Conclusions: TCJ (150 mg/kg) and its main component, carvacrol, could somewhat reduce cisplatin-induced nephrotoxicity through their anti-inflammatory, antioxidant, and anti-apoptotic effects.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141681509","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}
Mohammad Mehdi Gravandi, Seyede Zahra Hosseini, Seyede Darya Alavi, Tayebeh Noori, Antoni Sureda, Roshanak Amirian, Mohammad Hosein Farzaei, Samira Shirooie
{"title":"The Protective Effects of <i>Pistacia Atlantica</i> Gum in a Rat Model of Aluminum Chloride-Induced Alzheimer's Disease via Affecting BDNF and NF-kB.","authors":"Mohammad Mehdi Gravandi, Seyede Zahra Hosseini, Seyede Darya Alavi, Tayebeh Noori, Antoni Sureda, Roshanak Amirian, Mohammad Hosein Farzaei, Samira Shirooie","doi":"10.5812/ijpr-142203","DOIUrl":"10.5812/ijpr-142203","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of <i>Pistacia atlantica</i> gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl<sub>3</sub>). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of <i>P. atlantica</i> gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl<sub>3</sub> group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl<sub>3</sub> exposure. Our findings suggest that <i>P. atlantica</i> gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618024","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":"RadioLabeling of the Mutant form of Anti-PlGF Nanobody by 99mTc-Tricarbonyl","authors":"Tahereh Rezazadeh, Akram Sadat Tabatabaee Bafroee, Soraya Shahhosseini, Safura Jokar, Abolfazl Hasanramezani, R. Arezumand","doi":"10.5812/ijpr-144901","DOIUrl":"https://doi.org/10.5812/ijpr-144901","url":null,"abstract":"Background: Molecular imaging is a highly effective method for diagnosing cancer and evaluating treatment. A molecular tracer often consists of two segments: A targeting segment, which can be antibodies, antibody fragments, or VHH (nanobody), and a detection segment, such as radioisotopes. The small size of VHH allows for excellent tissue penetration and fast clearance, resulting in minimal nonspecific background, which makes them appealing for use as imaging agents. 99m-technetium (99mTc), one of the well-known radioisotopes, is particularly useful in routine clinical imaging. Objectives: This study aims to construct 99mTc-anti-placenta growth factor (PlGF) nanobody and assess its radiochemical purity (RCP). Methods: The mutant form of anti-PlGF nanobody was expressed in E. coli TG1 and purified using Ni-NTA column affinity chromatography. The purified nanobodies were confirmed by SDS-PAGE and western blotting. A 99mTc-tricarbonyl solution was added to phosphate-buffered saline (PBS) containing the mutant nanobody for labeling, and the mixture was purified using a PD-10 column. Results: The RCP of 99mTc-tricarbonyl is > 98%. After the addition of radioisotopes to the mixture of nanobodies, purity reached 70% in 2 hours and remained constant during incubation. After purifying the labeled nanobody, activity was measured, and the highest amount of labeled nanobodies was collected in the second part. The stability of the labeled nanobody in PBS and in competition with histidine for 4 hours was checked by thin-layer chromatography (TLC). Conclusions: The findings of this study reveal that the RCP of the labeled nanobody was above 95% after 4 hours, indicating the labeled antibody's stability. These results are promising and could be utilized in future in vitro and in vivo studies.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272863","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":"Bioinformatics and Gene Expression Omnibus Analysis of Key Candidate Genes and Pathways Associated with Femoral Head Necrosis","authors":"Yuanjing Ding, Yuxia Ma, Heng Yan, Enshui Zhang","doi":"10.5812/ijpr-145223","DOIUrl":"https://doi.org/10.5812/ijpr-145223","url":null,"abstract":"Background: Femoral head necrosis (FHN) is a debilitating bone disease affecting an estimated 8 million people worldwide. Although specific drugs for FHN have limitations, targeted therapies have shown promising results. The significance of this study is underscored by the high prevalence of FHN, the limitations of current treatments, and the potential of targeted drugs and natural compounds for effective therapeutic interventions. Objectives: This study aimed to explore the genetic landscape and associated pathways of FHN through bioinformatics analysis of Gene Expression Omnibus (GEO) data and molecular docking simulations targeting specific enzymes implicated in FHN. Methods: Differentially expressed genes (DEGs) in FHN samples were identified from GEO datasets, specifically accession number GSE123568 (Platform: GPL15207). Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify enriched pathways and Gene Ontology (GO) terms. Additionally, a protein-protein interaction (PPI) network was constructed using the STITCH (search tool for interaction of chemicals) database, which helped identify top hub genes and proteins. Molecular docking was conducted against key proteins using compounds from the topical chinese herbal medicine (TCHM) database associated with FHN. Results: The study provided a comprehensive bioinformatics analysis of key candidate genes and pathways associated with FHN, which may serve as potential therapeutic targets. It was found that FHN is associated with mitogen-activated protein kinases (MAP4K4/ MAPK8/ MAPK9) and interleukins (IL1b/ IL19/ IL26). Molecular docking results showed strong interactions of traditional Chinese herbal compounds through hydrogen bonding and electrostatic interactions at the active sites of the top ten target proteins associated with FHN. Conclusions: The study confirmed that FHN is linked with enzymes such as mitogen-activated protein kinases (MAPKs), interleukins, tumor necrosis factors (TNFs), and VEGFA (vascular endothelial growth factor A). Molecular docking simulations demonstrated that hesperidin, naringin, and curcumin exhibit potent inhibition against key proteins involved in FHN. Future research will focus on elucidating the specific roles of genes associated with FHN and exploring potential therapeutic targets using natural compounds.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141272809","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}
MohammadReza Raeisi, Abdolkarim Zamani Moghaddam, Seyyed sattar Tohidifar, Maryam Malekan
{"title":"Administering Fluralaner in Drinking Water for Treatment of Dermanyssus gallinae Infestation in Hy-Line W80 Laying Hens","authors":"MohammadReza Raeisi, Abdolkarim Zamani Moghaddam, Seyyed sattar Tohidifar, Maryam Malekan","doi":"10.5812/ijpr-145526","DOIUrl":"https://doi.org/10.5812/ijpr-145526","url":null,"abstract":"Background: Poultry red mites, or Dermanyssus gallinae, pose a threat to the welfare and productivity of laying hens. Moreover, the increasing resistance of these mites to conventional miticides highlights the urgent need for alternative treatment options. There are also documented cases of poultry red mite infestations in humans. Objectives: The primary objective of this study was to evaluate the efficacy of fluralaner against Dermanyssus gallinae infestation in hens. Methods: Fluralaner was selected as a novel treatment for poultry red mite due to its effectiveness and safety profile. The presence of live mites in the drinking water tank served as the indicator of infestation. Live mites were counted on nine occasions throughout the study. Fluralaner was administered at three doses of 0.5 mg/kg in drinking water with a seven-day interval between each dose. The efficacy of fluralaner was assessed, with an efficacy percentage exceeding 90% considered indicative of antiparasitic efficacy. Results: The overall efficacy of Fluralaner in the current study exceeded 90% by day 5 and reached 100% by day 17. Conclusions: This study demonstrates that fluralaner is an effective alternative treatment, achieving efficacy rates exceeding 90% against poultry red mite infestation in laying hens.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141274058","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}
Ali Homayouni, S. Nikfar, Fariborz Mokarian Rajabi, Mona Nili, Kimberly M. Kelly, Akbar Abdollahiasl
{"title":"Systematic Review of Patient Preference Studies in Non-metastatic Breast Cancer Adjuvant Medication Therapy: Attribute Selection","authors":"Ali Homayouni, S. Nikfar, Fariborz Mokarian Rajabi, Mona Nili, Kimberly M. Kelly, Akbar Abdollahiasl","doi":"10.5812/ijpr-144877","DOIUrl":"https://doi.org/10.5812/ijpr-144877","url":null,"abstract":"Context: Breast cancer poses significant challenges due to its high incidence and prevalence, necessitating heightened attention. Understanding how patients prioritize different treatment options based on various attributes can assist healthcare decision-makers in maximizing patient utility. The discrete choice experiment, a conjoint method, facilitates preference elicitation by presenting different attributes and choices. This systematic review aims to identify key factors in patient preference research related to adjuvant treatment for early breast cancer characterized by hormone receptor-positive, HER2-negative status. Evidence Acquisition: PubMed, Embase, Web of Science, and Scopus were searched from 01.01.2000 to 31.03.2023. Original English articles reporting patient preferences in adjuvant breast cancer treatment were retrieved based on predefined inclusion and exclusion criteria. Included studies were examined through a narrative synthesis approach, with descriptive statistics employed for analysis. Results: Out of 1163 articles reviewed, four met the inclusion criteria and were conducted in the USA, Canada, and the Netherlands. Attributes extracted from all studies included alopecia, sensory neuropathy, motor neuropathy, myalgia/arthralgia, nausea, vomiting, fatigue, neutropenia, mucositis/stomatitis, hand-foot syndrome, diarrhea, prevention of breast cancer recurrence, osteoporosis, risk of endometrial cancer, joint and muscle pain, fluid retention, libido decrease, hot flashes, ECG monitoring, efficacy, treatment regimen, 5-year invasive disease-free survival (iDFS), dosing schedule, and treatment duration. The most frequently reported attributes were side effects, efficacy, and treatment regimen. Systematic review was commonly used to determine which attributes and levels to include. The minimum number of attributes identified per study was seven, and the maximum was 12. Sample sizes ranged from 102 to 300, with none of the studies mentioning the method of sample size estimation. Ordinary Least Squares, logistic regression, and hierarchical Bayes regression were the most frequent analysis methods. Conclusions: Side effects, 5-year iDFS, and treatment regimen are three attributes identified for conducting discrete choice experiment studies. Utilizing conjoint analysis to assess patient preferences for breast cancer treatment can aid in selecting optimal treatment regimens and improving patient adherence. Moreover, adhering to guidelines for developing experimental designs and conducting data analysis is essential for yielding robust results when employing preference elicitation methods.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277535","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}
M. Roghani, Ravieh Golchoobian, Maryam Mohammadian, Farzane Shanehbandpour-Tabari, Zahra Salehi, Saba Gilaki-Bisheh
{"title":"Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity","authors":"M. Roghani, Ravieh Golchoobian, Maryam Mohammadian, Farzane Shanehbandpour-Tabari, Zahra Salehi, Saba Gilaki-Bisheh","doi":"10.5812/ijpr-145483","DOIUrl":"https://doi.org/10.5812/ijpr-145483","url":null,"abstract":": The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141125677","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}
Homa Hemati, M. Nosrati, M. Hasanzad, Parham Rahmani, Soroush Fariman, Mohadese Sarabi, Sepideh Shirvani, P. Sadeghipour, S. Nikfar
{"title":"Cost-Effectiveness Analysis of Pharmacogenomics-Guided Versus Standard Dosing of Warfarin in Patients with Mechanical Prosthetic Heart Valve","authors":"Homa Hemati, M. Nosrati, M. Hasanzad, Parham Rahmani, Soroush Fariman, Mohadese Sarabi, Sepideh Shirvani, P. Sadeghipour, S. Nikfar","doi":"10.5812/ijpr-143898","DOIUrl":"https://doi.org/10.5812/ijpr-143898","url":null,"abstract":"Background: Warfarin is the only approved anticoagulant for antithrombotic treatment in patients with mechanical prosthetic heart valves (MPHV). However, dosing warfarin is challenging due to its narrow therapeutic window and highly variable clinical outcomes. Both low and high doses of warfarin can lead to thrombotic and bleeding events, respectively, with these complications being more severe in individuals with sensitive genetic polymorphisms. Incorporating genetic testing could enhance the accuracy of warfarin dosing and minimize its adverse events. Objectives: This study aims to evaluate the utilities and cost-effectiveness of pharmacogenomics-guided versus standard dosing of warfarin in patients with MPHV in Iran. Methods: In this economic evaluation study, a cost-effectiveness analysis was conducted to compare pharmacogenomics-guided versus standard warfarin dosing. Data related to quality of life (QoL) were collected through a cross-sectional study involving 105 randomly selected MPHV patients using the EuroQol-5D (EQ-5D) Questionnaire. Costs were calculated with input from clinical experts and a review of relevant guidelines. Additional clinical data were extracted from published literature. The pharmacoeconomic threshold set for medical interventions within Iran's healthcare system was $1,500. A decision tree model was designed from the perspective of Iran's healthcare system with a one-year study horizon. Sensitivity analyses were also performed to assess the uncertainty of input parameters. Results: The utility scores derived from the questionnaire for standard and pharmacogenomics-guided warfarin treatments were 0.68 and 0.76, respectively. Genotype-guided dosing of warfarin was more costly compared to the standard dosing ($246 vs $69), and the calculated incremental cost-effectiveness ratio (ICER) was $2474 per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that our model is sensitive to the percentage of time in the therapeutic range (PTTR), the cost of genetic tests, and the utility of both pharmacogenomics-guided and standard dosing arms. However, the probabilistic sensitivity analysis demonstrates the robustness of our model. Conclusions: Warfarin dosing with pharmacogenomics testing is currently not cost-effective. However, if the cost of genotyping tests decreases to $118, the ICER would become cost-effective.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140979229","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}
Farzane Shanehbandpour-Tabari, Fatemeh Gholamnataj, N. Neamati, Ebrahim Zabihi, Farideh Feizi, Hadi Parsian
{"title":"Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice","authors":"Farzane Shanehbandpour-Tabari, Fatemeh Gholamnataj, N. Neamati, Ebrahim Zabihi, Farideh Feizi, Hadi Parsian","doi":"10.5812/ijpr-142903","DOIUrl":"https://doi.org/10.5812/ijpr-142903","url":null,"abstract":"Background: Benzo(a)pyrene (BaP), an environmental toxicant and endocrine disruptor, has been shown to exacerbate atherosclerosis when combined with a high-fat diet. Fibroblast Growth Factor-21 (FGF21), a novel hormone with anti-atherosclerotic properties, is associated with the presence of atherosclerosis and reduces plaque formation in experimental animals. Objectives: The present study aimed to investigate the chronic effect of BaP injection on hepatic FGF21 expression, as an anti-atherosclerotic hormone, in mice fed with or without an atherogenic diet (AtD). Methods: Eighteen C57BL/6J male mice (6 weeks) were randomly divided into six groups based on the dosage and diet. Blood samples were collected, and serum cholesterol, triglyceride, HDL-C, LDL-C, and glucose levels were measured. FGF21 expression was assessed by quantitative real-time PCR. Atherosclerotic lesions in mice were studied with Oil Red O (ORO) staining. Results: Benzo(a)pyrene causes a significant increase in liver FGF21 expression in a dose-dependent manner, and BaP co-exposure with AtD leads to a further increase in FGF21 expression. Additionally, the addition of BaP to AtD significantly increased the serum glucose, cholesterol, and LDL-C levels and accelerated the formation of atherosclerotic lesions. Besides, our findings showed that there is a significant positive correlation between FGF21 expression and glucose, cholesterol, LDL-C, and ORO-positive areas. Conclusions: Our findings revealed that BaP increases the expression of endogenous FGF21 in treated animals as a compensatory response to protect the heart from atherosclerosis induced by BaP and AtD.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140988902","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}
B. Seifi, Mehri Kadkhodaei, E. Bakhshi, Abdollah Sajedizadeh, M. Ranjbaran, Mahdi Hajiaqaei
{"title":"PAG Masked Protective Physical Exercise-Induced High H2S Levels in 5/6 Nephrectomized Rats","authors":"B. Seifi, Mehri Kadkhodaei, E. Bakhshi, Abdollah Sajedizadeh, M. Ranjbaran, Mahdi Hajiaqaei","doi":"10.5812/ijpr-145620","DOIUrl":"https://doi.org/10.5812/ijpr-145620","url":null,"abstract":"Background: To investigate the mechanisms of exercise therapeutics in preclinical animal models of chronic kidney disease (CKD), PAG (D, L-propargylglycine), an inhibitor of hydrogen sulfide production, was used to examine the protective effects of physical activity on oxidative stress and inflammation levels during CKD. Methods: Male Wistar rats with CKD, induced by the 5/6 nephrectomy procedure and subjected to 8 weeks of exercise training, received injections of PAG, a cystathionine γ-lyase (CSE) inhibitor, at a dose of 19 mg/kg, i.p., twice a week during those 8 weeks. The systolic blood pressure (BP) and renal sympathetic nerve activity (RSNA) were assessed. Additionally, plasma creatinine, BUN, renal hydrogen sulfide (H2S) levels, oxidative stress, and inflammatory markers were evaluated. Results: In the PAG group, inhibition of H2S production significantly reversed the improvements in plasma creatinine, BUN, renal malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, TNF-α, and IL-6 that were achieved by exercise. Additionally, high RSNA and high BP, which were also reversed in the PAG group, compared to the CKD group subjected to exercise training. Conclusions: The results suggest that the improvement in BP, oxidative stress, and inflammation status by exercise in CKD may be at least partially due to CSE/H2S signaling.","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140988091","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}