Immunopharmacology and Immunotoxicology最新文献

{"title":"Systematic Review of the Efficacy and Safety of Lenvatinib in Various Solid Tumors","authors":"Shuai Geng, Tong Liu, Nan Wang, Xinyue Gao, Xinyu Luo, Ning Shi, Shuai Jiang","doi":"10.1080/08923973.2024.2344153","DOIUrl":"https://doi.org/10.1080/08923973.2024.2344153","url":null,"abstract":"Objective The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. Method By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang an...","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"49 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609392","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":"CCL2 regulated by the CTBP1-AS2/miR-335-5p axis promotes hemangioma progression and angiogenesis","authors":"Ruixuan Li, Ying Liu, Jianfeng Liu, Bo Chen, Zhongjie Ji, Aixia Xu, Tianhua Zhang","doi":"10.1080/08923973.2024.2330651","DOIUrl":"https://doi.org/10.1080/08923973.2024.2330651","url":null,"abstract":"Context: Hemangioma (HA) is a benign vascular neoplasm that can lead to permanent scarring. C-C motif chemokine ligand 2 (CCL2) plays a crucial role in facilitating growth and angiogenesis during H...","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"158 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583415","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":"AFM₁ exposure in male balb/c mice and intervention strategies against its immuno-physiological toxicity using clay mineral and lactic acid bacteria alone or in combination.","authors":"Amina Aloui, Jalila Ben Salah-Abbès, Hela Belgacem, Haifa Dhif, Abdellah Zinedine, Amar Riba, Jean Christophe Meile, Noel Durande, Catherine Brabet, Samir Abbès","doi":"10.1080/08923973.2023.2300299","DOIUrl":"10.1080/08923973.2023.2300299","url":null,"abstract":"<p><strong>Context: </strong>Aflatoxins are the most harmful mycotoxins that cause human and animal health concerns. Aflatoxin M<sub>1</sub> (AFM<sub>1</sub>) is the primary hydroxylated metabolite of aflatoxin B<sub>1</sub> and is linked to the development of hepatocellular carcinoma and immunotoxicity in humans and animals. Because of the important role of dairy products in human life, especially children, AFM<sub>1</sub> is such a major concern to humans because of its frequent occurrence in dairy products at concentrations high enough to cause adverse effects to human and animal health. Reduced its bioavailability becomes a high priority in order to protect human and animal health.</p><p><strong>Objectives: </strong>This study aimed to investigate, <i>in vivo</i>, the ability of lactic acid bacteria (<i>lactobacillus rhamnosus</i> GAF01, LR) and clay mineral (bentonite, BT) mixture to mitigate/reduce AFM<sub>1</sub>-induced immunotoxicity, hepatotoxicity, nephrotoxicity and oxidative stress in exposed Balb/c mice.</p><p><strong>Materials and methods: </strong>The <i>in vivo</i> study was conducted using male Balb/c mice that treated, orally, by AFM<sub>1</sub> alone or in combination with LR and/or BT, daily for 10 days as follows: group 1 control received 200 µl of PBS, group 2 treated with LR alone (2.10<sup>8</sup> CFU/mL), group 3 treated with BT alone (1 g/kg bw), group 4 treated with AFM<sub>1</sub> alone (100 μg/kg), group 5 co-treated with LR + AFM<sub>1</sub>, group 6 co-treated with BT + AFM<sub>1</sub>, group 7 co-treated with BT + LR + AFM<sub>1</sub>. Forty-eight h after the end of the treatment, the mice were sacrificed and the blood, spleen, thymus, liver and kidney were collected. The blood was used for biochemical and immunological study. Spleen and thymus samples were used to thymocytes and splenocytes assessments. Liver and kidney samples were the target for evaluation of oxidative stress enzymes status and for histological assays.</p><p><strong>Results: </strong>The results showed that AFM<sub>1</sub> caused toxicities in male Blab/c mice at different levels. Treatment with AFM<sub>1</sub> resulted in severe stress of liver and kidney organs indicated by a significant change in the biochemical and immunological parameters, histopathology as well as a disorder in the profile of oxidative stress enzymes levels. Also, it was demonstrated that AFM<sub>1</sub> caused toxicities in thymus and spleen organs. The co-treatment with LR and/or BT significantly improved the hepatic and renal tissues, regulated antioxidant enzyme activities, spleen and thymus viability and biochemical and immunological parameters. LR and BT alone showed to be safe during the treatment.</p><p><strong>Conclusion: </strong>In summary, the LR and/or BT was able to reduce the biochemical, histopathological and immunological damages induced by AFM<sub>1</sub> and indeed it could be exploited as one of the biological strategies for food and feedstuffs detoxif","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"199-211"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048678","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":"Eosinophil to lymphocyte ratio may predict OCS reduction and change in quality of life (AQLQ) resulting from asthma biological treatment.","authors":"Olga Branicka, Radosław Gawlik, Joanna Glück","doi":"10.1080/08923973.2023.2300300","DOIUrl":"10.1080/08923973.2023.2300300","url":null,"abstract":"<p><strong>Objectives: </strong>Simple clinical parameters that could be helpful in choice of monoclonal antibodies and prediction of their effectiveness are being sought. The aim was to assess if neutrophil-to-lymphocyte, eosinophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict outcomes of biologic therapy for severe asthma.</p><p><strong>Methods: </strong>Retrospective, single-center study including severe asthma patients treated with three different biologics. The blood ratios were assessed at initiation of treatment (point 0) and after six months (point 1). The chi-square test was used to analyze differences in nominal variables. Quantitative variables were compared by Student's <i>t</i>-test, Mann-Whitney <i>U</i> or Wilcoxon signed-rank tests.</p><p><strong>Results: </strong>53 patients with severe asthma were included, among them 21 patients (40%) treated with omalizumab and 32 patients (60%) with mepolizumab or benralizumab. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios did not change during six-month-course of biological treatment. Eosinophil-to-lymphocyte ratio was higher at the point 0 (<i>p</i> = 0.016) in the group treated with anti-eosinophils than in the omalizumab group and lower at the point 1 (<i>p</i> = 0.006). In the anti-eosinophil group this ratio decreased between points 0 and 1 (<i>p</i> < 0.001). In the omalizumab group there was an inverse correlation between the initial ratio and oral corticosteroid dose reduction (r_s = -0,67). In the a/eos group there were significant correlations between initial ratio and age (r_s = 0.36), and ACQ (r_s = -0.4) and ACQ (r_s = 0.41) measured at the point 1.</p><p><strong>Conclusions: </strong>Pretreatment eosinophil-to-lymphocyte ratio may predict oral corticosteroid dose reduction resulting from omalizumab treatment and change in quality of life and asthma control resulting from anti-IL-5 and IL-5R treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"212-217"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048679","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":"The potential role of hydrogen sulfide in regulating macrophage phenotypic changes via PINK1/parkin-mediated mitophagy in sepsis-related cardiorenal syndrome.","authors":"Yuxuan Chen, Wei Cao, Bin Li, Xiaofei Qiao, Xiangdong Wang, Guang Yang, Siying Li","doi":"10.1080/08923973.2023.2281901","DOIUrl":"10.1080/08923973.2023.2281901","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis is one of major reasons of cardiorenal syndrome type 5 (CRS-5), resulting in irreversible tissue damage and organ dysfunction. Macrophage has been demonstrated to play key role in the pathophysiology of sepsis, highlighting the need to identify therapeutic targets for modulating macrophage phenotype in sepsis.</p><p><strong>Methods and results: </strong>In this study, a rapid-releasing hydrogen sulfide (H2S) donor NaSH, and a slow-releasing H2S compound S-propargyl-cysteine (SPRC) which is derived from garlic, have been studied for the immune-regulatory effects on macrophages. The NaSH and SPRC showed the potential to protect the heart and kidney from tissue injury induced by LPS. The immunohistochemistry of F4/80+ revealed that the infiltration of macrophages in the heart and kidney tissues of LPS-treated mice was reduced by NaSH and SPRC. In addition, in the LPS-triggered inflammatory cascade of RAW264.7 macrophage cells, NaSH and SPRC exhibited significantly inhibitory effects on the secretion of inflammatory cytokines, production of reactive oxygen species (ROS), and regulation of the macrophage phenotype from M1-like to M2-like. Moreover, autophagy, a crucial process involved in the elimination of impaired proteins and organelles during oxidative stress and immune response, was induced by NaSH and SPRC in the presence of LPS stimulation. Consequently, there was an increase in the number of mitochondria and an improvement in mitochondrial membrane potential. This process was mainly mediated by PINK1/Parkin pathway mediated mitophagy.</p><p><strong>Discussion: </strong>These results demonstrated that the immunoregulatory effects of H2S donors were through the PINK1/Parkin-mediated mitophagy pathway. Overall, our study provided a new therapeutic direction in LPS-induced cardiorenal injury.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"139-151"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397244","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":"Cycloastragenol restrains keratinocyte hyperproliferation by promoting autophagy via the miR-145/STC1/Notch1 axis in psoriasis.","authors":"Jie Xia, Yuan Zhang, Qing Wang, Teng Zhang","doi":"10.1080/08923973.2023.2300310","DOIUrl":"10.1080/08923973.2023.2300310","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is characterized by inflammation and hyperproliferation of epidermal keratinocytes. Cycloastragenol (CAG) is an active molecule of <i>Astragalus membranaceus</i> that potentially plays a repressive role in psoriasis. Activated cell autophagy is an effective pathway for alleviating psoriasis progression. Thus, we investigated the role of CAG in the proliferation and autophagy of interleukin (IL)-22-stimulated keratinocytes.</p><p><strong>Methods: </strong>A psoriasis model was established by stimulating HaCaT cells with IL-22. Gene or protein expression levels were measured by qRT-PCR or western blot. Autophagy flux was observed with mRFP-GFP-LC3 adenovirus transfection assay under confocal microscopy. Stanniocalcin-1 (STC1) secretion levels were determined using ELISA kits. The apoptosis rate was assessed using flow cytometry. Interactions between miR-145 and STC1 or STC1 and Notch1 were validated by luciferase reporter gene assays, RIP, and Co-IP assays.</p><p><strong>Results: </strong>CAG repressed cell proliferation and promoted apoptosis and autophagy in IL-22-stimulated HaCaT cells. Additionally, CAG promoted autophagy by enhancing miR-145. STC1 silencing ameliorated autophagy repression in IL-22-treated HaCaT cells. Moreover, miR-145 negatively regulated STC1, and STC1 was found to activate Notch1. Lastly, STC1 overexpression reversed CAG-promoted autophagy.</p><p><strong>Conclusion: </strong>CAG alleviated keratinocyte hyperproliferation through autophagy enhancement <i>via</i> regulating the miR-145/STC1/Notch1 axis in psoriasis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"229-239"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402638","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":"Thiolutin, a selective NLRP3 inflammasome inhibitor, attenuates cyclophosphamide-induced impairment of sperm and fertility in mice.","authors":"Pengfei Zhu, Xingyu Bi, Dan Su, Xiaoling Li, Bingbing Chen, Juhua Li, Lijiang Zhao, Yaoqing Wang, Suming Xu, Xueqing Wu","doi":"10.1080/08923973.2023.2298894","DOIUrl":"10.1080/08923973.2023.2298894","url":null,"abstract":"<p><strong>Objective: </strong>The activation of the NLRP3 inflammasome has been implicated in male infertility. Our study aimed to investigate the therapeutic role of Thiolutin (THL), an inhibitor of the NLRP3 inflammasome, on oligoasthenospermia (OA) and to elucidate its mechanisms.</p><p><strong>Materials and methods: </strong>Semen from 50 OA and 20 healthy males were analyzed to assess the sperm quality and levels of inflammatory markers. Their correlation was determined using Pearson's correlation coefficient. The BALB/c mice were intraperitoneal injected by cyclophosphamide at 60 mg/kg/day for five days to induce OA, followed by a two-week treatment with THL or L-carnitine. Reproductive organ size and H&E staining were determined to observe the organ and seminiferous tubule morphology. ELISA and western blotting were utilized to measure sex hormone levels, inflammatory markers, and NLRP3 inflammasome levels. Furthermore, male and female mice were co-housed to observe pregnancy success rates.</p><p><strong>Results: </strong>OA patients exhibited a decrease in sperm density and motility compared to healthy individuals, along with elevated levels of IL-1β, IL-18 and NLRP3 inflammasome. <i>In vivo</i>, THL ameliorated OA-induced atrophy of reproductive organs, hormonal imbalance, and improved sperm density, motility, spermatogenesis and pregnancy success rates with negligible adverse effects on weight or liver-kidney function. THL also demonstrated to be able to inhibit the activation of NLRP3 inflammasome and associated proteins in OA mice.</p><p><strong>Discussion: </strong>THL can improve sperm quality and hormonal balance in OA mice through the inhibition of NLRP3 inflammasome activation. Thus, THL holds promising potential as a therapeutic agent for OA.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"172-182"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086699","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":"Endoplasmic reticulum stress is upregulated in inflammatory bowel disease and contributed TLR2 pathway-mediated inflammatory response.","authors":"Weijie Wu, Yan Zhao, Tian Hu, Yan Long, Ya Zeng, Mengling Li, Siyuan Peng, Jinyue Hu, Yueming Shen","doi":"10.1080/08923973.2023.2298897","DOIUrl":"10.1080/08923973.2023.2298897","url":null,"abstract":"<p><strong>Objective: </strong>Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether Thapsigargin (TG) -induced ER protein expression levels contributed to TLR2-mediated inflammatory response.</p><p><strong>Methods: </strong>The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer Thapsigargin (TG) or inhibitor (TUDCA). The mRNA expressions of TLR1-TLR10 were detected by qPCR. The production and secretion of inflammatory factors were detected by PCR and ELISA. Immunohistochemistry was used to detect the expressions of GRP78 and TLR2 in the intestinal mucosa of patients with Crohn's disease (CD). The IBD mouse model was established by TNBS in the modeling group. ERS inhibitor (TUDCA) was used in the treatment group.</p><p><strong>Results: </strong>The expression of TLRs was detected via polymerase chain reaction (PCR) in THP-1 cells treated by ERS agonist Thapsigargin (TG). According to the findings, TG could promote TLR2 and TLR5 expression. Subsequently, in TLR2 agonist Pam3CSK4 induced THP-1 cells, TG could lead to increased expression of the inflammatory factors such as TNF-α, IL-1β and IL-8, and ERS inhibitor (TUDCA) could block this effect. However, Pam3CSK4 did not significantly impact the GRP78 and CHOP expression. Based upon the immunohistochemical results, TLR2 and GRP78 expression were significantly increased in the intestinal mucosa of patients with Crohn's disease (CD). For in vivo experiments, TUDCA displayed the ability to inhibit intestinal mucosal inflammation and reduce GRP78 and TLR2 proteins.</p><p><strong>Conclusions: </strong>ERS and TLR2 is upregulated in inflammatory bowel disease, ERS may promote TLR2 pathway-mediated inflammatory response. Moreover, ERS and TLR2 signaling could be novel therapeutic targets for IBD.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"192-198"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037554","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":"The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response.","authors":"Jianfeng Yao, Tao Sun, Songbai Zheng, Jianxia Ma, Qinglian Zeng, Kangwei Liu, Wei Zhang, Yang Yu","doi":"10.1080/08923973.2024.2308252","DOIUrl":"10.1080/08923973.2024.2308252","url":null,"abstract":"<p><strong>Objective: </strong>Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This <i>in vitro</i> and <i>in vivo</i> study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms.</p><p><strong>Methods: </strong>Human intestinal epithelial cells (Caco-2 cells) serve as the <i>in vitro</i> experimental model. Lipopolysaccharide (LPS, 1 μg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the <i>in vivo</i> assay.</p><p><strong>Results: </strong>Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 μg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, <i>Fusobacterium</i>, <i>Escherichia coli</i>, <i>Porphyromonas gingivalis</i> elevation, and <i>Mogibacterium timidum</i> decline in UC rats were inhibited by teprenone.</p><p><strong>Conclusion: </strong>Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"255-263"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512391","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":"Ivermectin ameliorates bleomycin-induced lung fibrosis in male rats by inhibiting the inflammation and oxidative stress.","authors":"Fatemeh Habibi Razi, Razieh Mohammad Jafari, Mohammad Amin Manavi, Mohammad Sheibani, Amir Rashidian, Seyed Mohammad Tavangar, Mohammad Taghi Beighmohammadi, Ahmad Reza Dehpour","doi":"10.1080/08923973.2023.2298895","DOIUrl":"10.1080/08923973.2023.2298895","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a pulmonary fibrotic disease characterized by a poor prognosis, which its pathogenesis involves the accumulation of abnormal fibrous tissue, inflammation, and oxidative stress. Ivermectin, a positive allosteric modulator of GABA_A receptor, exerts anti-inflammatory and antioxidant properties in preclinical studies. The present study investigates the potential protective effects of ivermectin treatment in rats against bleomycin-induced IPF.</p><p><strong>Materials and methods: </strong>The present study involved 42 male Wistar rats, which were divided into five groups: control (without induction of IPF), bleomycin (IPF-induced by bleomycin 2.5 mg/kg, by intratracheal administration), and three fibrosis groups receiving ivermectin (0.5, 1, and 3 mg/kg). lung tissues were harvested for measurement of oxidative stress [<i>via</i> myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH)] and inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and transforming growth factor-β [TGF-β]). Histological assessments of tissue damage were performed using hematoxylin-eosin (H&E) and Masson's trichrome staining methods.</p><p><strong>Results: </strong>The induction of fibrosis <i>via</i> bleomycin was found to increase levels of MPO as well as TNF-α, IL-1β, and TGF-β while decrease SOD activity and GSH level. Treatment with ivermectin at a dosage of 3 mg/kg was able to reverse the effects of bleomycin-induced fibrosis on these markers. In addition, results from H&E and Masson's trichrome staining showed that ivermectin treatment at this same dose reduced tissue damage and pulmonary fibrosis.</p><p><strong>Conclusion: </strong>The data obtained from this study indicate that ivermectin may have therapeutic benefits for IPF, likely due to its ability to reduce inflammation and mitigate oxidative stress-induced toxicity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"183-191"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465879","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}