Immunopharmacology and Immunotoxicology最新文献

{"title":"The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats.","authors":"Muhammed Fatih Doğan,&nbsp;Kürşat Kaya,&nbsp;Hasan Hüseyin Demirel,&nbsp;Mehmet Başeğmez,&nbsp;Yasemin Şahin,&nbsp;Osman Çiftçi","doi":"10.1080/08923973.2023.2181712","DOIUrl":"10.1080/08923973.2023.2181712","url":null,"abstract":"<p><p><b>Background:</b> Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC).<b>Methods:</b> A total of 40 Sprague-Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes.<b>Results:</b> FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (<i>p</i> < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (<i>p</i> < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (<i>p</i> < .05).<b>Conclusion:</b> FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9297211","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":"Effects of <i>Trigonella foenum graecum</i> (fenugreek) on rheumatoid arthritis: a systematic review.","authors":"Zeinab Faghfoori,&nbsp;Zeinab Javadivala,&nbsp;Yeganeh Khalili,&nbsp;Aida Malek Mahdavi","doi":"10.1080/08923973.2023.2202298","DOIUrl":"10.1080/08923973.2023.2202298","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant therapies especially medicinal plants have gained lots of attention nowadays and have been consumed all over the world for treating different diseases particularly rheumatoid arthritis (RA). Recent animal studies have indicated the benefits of fenugreek in RA and indicate that it may be a therapeutic candidate in RA; nonetheless, no systematic review is available about fenugreek and RA. This paper systematically reviewed the existing studies about fenugreek and RA and plausible mechanisms.</p><p><strong>Methods: </strong>Databases including PubMed, Scopus, Web of Science, ProQuest, and the search engine Google Scholar were searched until May 2022 and search alerts were used to receive studies issued after the primary search. There was no restriction in time and/or language. No human and <i>in vitro</i> research was detected; thus, animal investigations were considered. Also, the citations or references of studies were searched for potential studies. Book chapters, review papers, and grey literature (e.g. conference abstracts, dissertations, and patents) were not included.</p><p><strong>Results: </strong>Finally, 11 studies were entered in this systematic review. Animal investigations showed that fenugreek had favorable effects in RA and could control this disease <i>via</i> attenuating inflammation, suppressing oxidative stress, and displaying anti-arthritic activity.</p><p><strong>Conclusion: </strong>Current review provides potent evidences about the efficacy of fenugreek in RA and elucidates the significance of more clinical investigations. HighlightsFenugreek had favorable effects in rheumatoid arthritis and could control this disease via attenuating inflammation, suppressing oxidative stress, and displaying anti-arthritic activity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9326401","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":"Decreasing REDD1 expression protects against high glucose-induced apoptosis, oxidative stress and inflammatory injury in podocytes through regulation of the AKT/GSK-3β/Nrf2 pathway.","authors":"Xiaojing Wang,&nbsp;Jing Yang,&nbsp;Wenxing Wang,&nbsp;Yun Li,&nbsp;Yue Yang","doi":"10.1080/08923973.2023.2183351","DOIUrl":"10.1080/08923973.2023.2183351","url":null,"abstract":"<p><strong>Objective: </strong>Our goal in this work was to investigate the possible role and mechanism of regulated in development and DNA damage response 1 (REDD1) in mediating high glucose (HG)-induced podocyte injury <i>in vitro</i>.</p><p><strong>Materials and methods: </strong>Mouse podocytes were stimulated with HG to establish HG injury model. Protein expression was examined by Western blotting. Cell viability was measured by cell counting kit-8 assay. Cell apoptosis was assessed by annexin V-FITC/propidium iodide and TUNEL apoptotic assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified by commercial kits. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were measured by ELISA.</p><p><strong>Results: </strong>A marked increase in REDD1 expression was observed in podocytes stimulated with HG. Reduced REDD1 expression strikingly restrained HG-induced increases in apoptosis, oxidative stress, and inflammation response in cultured podocytes. Decreasing REDD1 expression enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HG-exposed podocytes <i>via</i> regulation of the AKT/glycogen synthase kinase-3 beta (GSK-3β) pathway. Inhibition of AKT or reactivation of GSK-3β prominently abolished Nrf2 activation induced by decreasing REDD1 expression. Pharmacological repression of Nrf2 markedly reversed the protective effects of decreasing REDD1 expression in HG-injured podocytes.</p><p><strong>Conclusion: </strong>Our data demonstrate that decreasing REDD1 expression protects cultured podocytes from HG-induced injuries by potentiating Nrf2 signaling through regulation of the AKT/GSK-3β pathway. Our work underscores the potential role of REDD1-mediated podocyte injury during the development of diabetic kidney disease.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10861187","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":"Two flavonoids, baicalein and naringin, are effective as anti-inflammatory and anti-oxidant agents in a rat model of polymicrobial sepsis.","authors":"Pinar Bayram,&nbsp;Selina Aksak Karamese,&nbsp;Bengul Ozdemir,&nbsp;Cagatay Salum,&nbsp;Huseyin Serkan Erol,&nbsp;Murat Karamese","doi":"10.1080/08923973.2023.2197143","DOIUrl":"10.1080/08923973.2023.2197143","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, our aim was to investigate the possible protective and therapeutic effects of these two flavonoids, baicalein, and naringin, in 50 and 100 mg/kg doses applied both before and after cecal ligation and puncture (CLP) procedures in a polymicrobial sepsis rat model, and evaluate the possible contribution of oxidative and inflammatory markers by immunological, biochemical, molecular, and histopathological methods.</p><p><strong>Methods: </strong>Sixty-six Wistar albino rats were divided into 11 groups. The pro-inflammatory (TNF-alpha, IL-1-beta, and IL-6) and anti-inflammatory (TGF-beta and IL-10) cytokine levels were measured by ELISA technique. CD3, CD68, and nuclear factor kappa B positivity rates were detected by immunohistochemical methods. Oxidative stress parameters (MDA, SOD, and GSH) were measured by tissue biochemistry.</p><p><strong>Results: </strong>Sepsis caused a significant increase in all pro-inflammatory cytokine levels and MDA activity. Also, it led to an increase in the positivities of CD3, CD68, and NF-κB markers. However, especially pre-CLP doses of baicalein and naringin inhibited the inflammation process by suppressing pro-inflammatory and increasing anti-inflammatory cytokine levels, as well as regulating the oxidative stress process by normalizing the oxidant/anti-oxidant enzyme levels.</p><p><strong>Conclusion: </strong>Both pre- and post-application of baicalein and naringin are quite effective to prevent sepsis-caused cellular processes. This protective and therapeutic effects by baicalein and naringin in animals with sepsis seems to be originated from the high antioxidant capacity and inhibition of pro-inflammatory cytokine production. Thus, those natural agents may prove to be valuable protective agent against septic shock.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9269256","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":"Correction.","authors":"","doi":"10.1080/08923973.2023.2193071","DOIUrl":"10.1080/08923973.2023.2193071","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177296","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":"Knockdown of A20 attenuates microglial susceptibility to OGD/R-induced ferroptosis and upregulates inflammatory responses.","authors":"Xiaorong Liu,&nbsp;Xiaomei Jin,&nbsp;Xianhui Wang,&nbsp;Xiaodan Yan,&nbsp;Chi Wang,&nbsp;Kaiyue Wang,&nbsp;Xiaoyan He,&nbsp;Wanqing Zhai","doi":"10.1080/08923973.2023.2189061","DOIUrl":"10.1080/08923973.2023.2189061","url":null,"abstract":"<p><p>The A20 protein is considered to have a potent anti-inflammatory effect, but its mechanism of action in the regulation of ferroptosis and inflammation after stroke is still unknown. In this study, the A20-knockdown BV2 cell line (sh-A20 BV2) was constructed at first, and the oxygen-glucose deprivation/re-oxygenation (OGD/R) cell model was constructed. Both the BV2 and sh-A20 BV2 cells were treated with the ferroptosis inducer erastin for 48 h, the ferroptosis-related indicators were detected by western blot. The mechanism of ferroptosis was explored by western blot and immunofluorescence. Under OGD/R pressure, the oxidative stress level of sh-A20 BV2 cells was inhibited, but the secretion of the inflammatory factors TNF-α, IL-1β, and IL-6 was significantly upregulated. And sh-A20 BV2 cells had higher expression levels of GPX4 and NLRP3 proteins under OGD/R induction. Western blot further confirmed that sh-A20 BV2 cells inhibited OGD/R-induced ferroptosis. Under the effect of erastin of the ferroptosis inducer (0-1000 nM), sh-A20 BV2 cells had higher cell viability than wild-type BV2 cells and significantly inhibited the accumulation of ROS and the level of oxidative stress damage. It was confirmed that A20 could promote the activation of the IκBα/NFκB/iNOS pathway. It was confirmed by an iNOS inhibitor that iNOS inhibition could reverse the resistance effect of BV2 cells to OGD/R-induced ferroptosis after A20 knockdown. In conclusion, this study demonstrated that inhibition of A20 mediates a stronger inflammatory response while enhancing microglial resistance by knocking down A20 in BV2 cells.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576527","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":"Exploring the role of ATP-sensitive potassium channel, eNOS, and P-glycoprotein in mediating the hepatoprotective activity of nicorandil in methotrexate-induced liver injury in rats.","authors":"Marwa M M Refaie,&nbsp;Maram El-Hussieny,&nbsp;Sayed Shehata,&nbsp;Nermeen N Welson,&nbsp;Walaa Yehia Abdelzaher","doi":"10.1080/08923973.2023.2201659","DOIUrl":"10.1080/08923973.2023.2201659","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its clinical use is challenged by various types of injuries, including hepatotoxic side effects. Therefore, finding new protective drugs against MTX-induced toxicities is a critical need. Moreover, the different mechanisms mediating such effects are still not clear. The current study aimed to evaluate the possible ameliorative action of nicorandil (NIC) in MTX-induced hepatotoxicity and examine the roles of the ATP-sensitive potassium channel (K_ATP), endothelial nitric oxide synthase (eNOS), and P-glycoprotein (P-gp).</p><p><strong>Materials and methods: </strong>Thirty-six male Wistar albino rats were used. NIC (3 mg/kg/day) was given orally for 2 weeks, and hepatotoxicity was induced by a single intraperitoneal injection of MTX (20 mg/kg) on the 11th day of the experiment. We confirmed the role of K_ATP by co-administering <i>glimepiride</i> (GP) (10 mg/kg/day) 30 min before NIC. The measured serum biomarkers were [alanine transaminase (ALT) and aspartate transaminase (AST)], total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NOx), tumor necrosis factor-alpha (TNFα), superoxide dismutase (SOD), and P-gp. Histopathology, eNOS, and caspase-3 immunoexpression were evaluated.</p><p><strong>Results: </strong>The MTX group displayed hepatotoxicity in the form of elevations of ALT, AST, MDA, NOx, and caspase-3 immunoexpression. Furthermore, the histopathological examination showed marked liver injury. TAC, SOD, P-gp, and eNOS immunoexpression showed significant inhibition. In the protective group, all parameters improved (P value < 0.05).</p><p><strong>Conclusion: </strong>NIC has an ameliorative action against MTX-induced hepatotoxicity, most probably <i>via</i> its antioxidant, anti-inflammatory, and anti-apoptotic functions together with the modulation of the K_ATP channel, eNOS, and P-glycoprotein.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9753937","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":"Evaluation of HER-2 positive breast cancer treated with dual-targeted treatment of trastuzumab plus pertuzumab.","authors":"Shuai Jiang,&nbsp;Shuai Geng,&nbsp;Xinyue Gao,&nbsp;Tong Liu,&nbsp;Xinyu Luo,&nbsp;Nan Wang,&nbsp;Ning Shi,&nbsp;Mei Dong","doi":"10.1080/08923973.2023.2183352","DOIUrl":"10.1080/08923973.2023.2183352","url":null,"abstract":"<p><p><b>Objective:</b> Clinical studies have shown that trastuzumab combined with pertuzumab (dual-targeted drug therapy) can significantly improve the treatment status and prognosis of HER-2 positive breast cancer patients through double targeting of HER-2. This study systematically evaluated the efficacy and safety of trastuzumab combined with pertuzumab in the treatment of HER-2 positive breast cancer.<b>Method:</b> We search relevant databases and collect RCTs on the treatment of HER-2 positive breast cancer with dual-targeted treatment. Meta-analysis was performed using Revman5.4 software.<b>Results:</b> A total of 10 studies for 8553 patients were included. Meta-analysis showed that, in terms of efficacy, overall survival (OS) (HR = 1.40, 95%CI = 1.29-1.53, <i>p</i> < 0.00001) and progression-free survival (PFS) (HR = 1.36, 95%CI = 1.28-1.46, <i>p</i> < 0.00001) in dual-targeted drug therapy were better than which in the single-targeted drug group. In terms of safety, the highest incidence (Relative risk, RR) of Adverse reactions was Infections and infestations (RR = 1.48, 95%CI = 1.24-1.77, <i>p</i> < 0.0001) follow by Nervous system disorders (RR = 1.29, 95%CI = 1.12-1.50, <i>p</i> = 0.0006), Gastrointestinal disorders (RR = 1.25, 95%CI = 1.18-1.32, <i>p</i> < 0.0001), Respiratory, thoracic, and mediastinal disorders (RR = 1.21, 95%CI = 1.01-1.46, <i>p</i> = 0.04), Skin and subcutaneous tissue disorders (RR = 1.14, 95%CI = 1.06-1.22, <i>p</i> = 0.0002) and General disorders (RR = 1.14, 95%CI = 1.04-1.25, <i>p</i> = 0.004) in dual-targeted drug therapy group. The incidence of Blood system disorder (RR = 0.94, 95%CI = 0.84-1.06, <i>p</i> = 0.32) and Liver dysfunction (RR = 0.80, 95%CI = 0.66-0.98, <i>p</i> = 0.03) was lower than that of the single targeted drug group.<b>Conclusion:</b> Dual-targeted treatment for HER-2-positive breast cancer can prolong the OS, PFS and improve the quality of patients' life. Meanwhile, it also brings a higher medication risk, which requires a rational selection of drug symptomatic interventions.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541430","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":"Phloroglucinol possesses anti-inflammatory activities by regulating AMPK/Nrf2/HO-1 signaling pathway in LPS-stimulated RAW264.7 murine macrophages.","authors":"Chathuri Kaushalya Marasinghe,&nbsp;Won-Kyo Jung,&nbsp;Jae-Young Je","doi":"10.1080/08923973.2023.2196602","DOIUrl":"10.1080/08923973.2023.2196602","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is closely related to the pathogenesis of chronic illnesses. Secondary metabolites of marine seaweeds are recognized as reliable sources of bioactive compounds due to their health benefits besides their nutritional value. The objective of this study was to determine the potential anti-inflammatory effect of phloroglucinol (Phl) in RAW264.7 murine macrophages after lipopolysaccharides (LPS) stimulation.</p><p><strong>Methods: </strong>MTT, nitric oxide (NO), and DCFH-DA assays were conducted to determine cell viability, NO production, and reactive oxygen species (ROS) generation respectively. Pro-inflammatory cytokines and prostaglandin E₂ (PGE₂) levels were measured using ELISA assay kits. Protein expression levels were determined by western blot analysis.</p><p><strong>Results: </strong>Phl treatment showed a promising anti-inflammatory effect by reducing NO production, secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), PGE₂ production, protein expression levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), and ROS generation in LPS-stimulated RAW264.7 murine macrophages. Phl treatment upregulated heme oxygenase-1 (HO-1) expression by inducing nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activating AMPK. However, Zinc protoporphyrin (ZnPP), an inhibitor of HO-1, partially reversed these effects, including NO production, pro-inflammatory cytokine secretion, iNOS, COX-2 and HO-1 expression, and ROS generation.</p><p><strong>Conclusion: </strong>Phl has potential anti-inflammatory activities by regulating AMPK/Nrf2/HO-1 pathway in LPS-stimulated RAW264.7 murine macrophages.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9269255","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":"Role of EGF/ERK1/2/HO-1 axis in mediating methotrexate induced testicular damage in rats and the ameliorative effect of xanthine oxidase inhibitors.","authors":"Remon Roshdy Rofaeil,&nbsp;Mohamed A Ibrahim,&nbsp;Reham H Mohyeldin,&nbsp;Nashwa F El-Tahawy,&nbsp;Walaa Yehia Abdelzaher","doi":"10.1080/08923973.2023.2181684","DOIUrl":"10.1080/08923973.2023.2181684","url":null,"abstract":"<p><p><b>Objectives:</b> Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. The current the protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats.<b>Materials and methods:</b> Thirty-two rats were randomly allocated to four groups; control (received vehicles), MTX (received single dose, 20 mg/kg, i.p.), MTX + ALL (received MTX plus ALL) and MTX + FEB (received MTX plus ALL). ALL and FEB were administered orally at 100- and 10 mg/kg, respectively for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and total nitrite/nitrate (NOx) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done.<b>Results:</b> ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NOx, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB.<b>Conclusion:</b> All and FEB were equally protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions. Their effects might be through activation of the EGF/ERK1/2/HO-1 pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10857686","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}