International Journal of Toxicology最新文献

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In vitro Safety Assessment of Extracts and Compounds From Plants as Sunscreen Ingredients. 植物提取物和化合物作为防晒成分的体外安全性评估。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-05-01 Epub Date: 2024-01-06 DOI: 10.1177/10915818231225661
Silvia Juliana Flórez González, Elena E Stashenko, Raquel Elvira Ocazionez, María Pilar Vinardell, Jorge Luis Fuentes
{"title":"In vitro Safety Assessment of Extracts and Compounds From Plants as Sunscreen Ingredients.","authors":"Silvia Juliana Flórez González, Elena E Stashenko, Raquel Elvira Ocazionez, María Pilar Vinardell, Jorge Luis Fuentes","doi":"10.1177/10915818231225661","DOIUrl":"10.1177/10915818231225661","url":null,"abstract":"<p><p>This work investigated the safety of extracts obtained from plants growing in Colombia, which have previously shown UV-filter/antigenotoxic properties. The compounds in plant extracts obtained by the supercritical fluid (CO<sub>2</sub>) extraction method were identified using gas chromatography coupled to mass spectrometry (GC/MS) analysis. Cytotoxicity measured as cytotoxic concentration 50% (CC<sub>50</sub>) and genotoxicity of the plant extracts and some compounds were studied in human fibroblasts using the trypan blue exclusion assay and the Comet assay, respectively. The extracts from <i>Pipper eriopodon</i> and <i>Salvia aratocensis</i> species and the compound <i>trans</i>-β-caryophyllene were clearly cytotoxic to human fibroblasts. Conversely, <i>Achyrocline satureioides</i>, <i>Chromolaena pellia</i>, and <i>Lippia origanoides</i> extracts were relatively less cytotoxic with CC<sub>50</sub> values of 173, 184, and 89 μg/mL, respectively. The <i>C. pellia</i> and <i>L. origanoides</i> extracts produced some degree of DNA breaks at cytotoxic concentrations. The cytotoxicity of the studied compounds was as follows, with lower CC<sub>50</sub> values representing the most cytotoxic compounds: resveratrol (91 μM) > pinocembrin (144 μM) > quercetin (222 μM) > titanium dioxide (704 μM). Quercetin was unique among the compounds assayed in being genotoxic to human fibroblasts. Our work indicates that phytochemicals can be cytotoxic and genotoxic, demonstrating the need to establish safe concentrations of these extracts for their potential use in cosmetics.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"243-252"},"PeriodicalIF":2.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110948","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}
引用次数: 0
Safety Assessment of Streptococcus salivarius UBSS-01 in Rats and Double-Blind Placebo-Controlled Study in Healthy Individuals 唾液链球菌 UBSS-01 在大鼠中的安全性评估和在健康人中的双盲安慰剂对照研究
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-27 DOI: 10.1177/10915818241247527
Bindhu S. Jatoth, Ziaur Rahman, Manoj P. Dandekar, Rajesh Venkataraman, Ravi K. Shivalingegowda, Gloriya G. Manuel
{"title":"Safety Assessment of Streptococcus salivarius UBSS-01 in Rats and Double-Blind Placebo-Controlled Study in Healthy Individuals","authors":"Bindhu S. Jatoth, Ziaur Rahman, Manoj P. Dandekar, Rajesh Venkataraman, Ravi K. Shivalingegowda, Gloriya G. Manuel","doi":"10.1177/10915818241247527","DOIUrl":"https://doi.org/10.1177/10915818241247527","url":null,"abstract":"Streptococcus salivarius is a common, harmless, and prevalent member of the oral microbiota in humans. In the present study, the safety of S. salivarius UBSS-01 was evaluated using in silico methods and preclinical and clinical studies. In an acute toxicity study, rats were administered with 5 g/kg (500 × 10<jats:sup>9</jats:sup> CFU) S. salivarius UBSS-01. The changes in phenotypic behaviors and hematological, biochemical, electrolytes, and urine analyses were monitored. No toxicity was observed at 14 days post-treatment. The no observable effects limit (NOEL) of S. salivarius UBSS-01 was &gt;5 g/kg in rats. In a 28-day repeat dose toxicity study, rats were administered S. salivarius UBSS-01 once daily at doses of 0.1, 0.5, and 1 g/kg (10, 50, and 100 billion CFU/kg, respectively) body weight. S. salivarius UBSS-01 did not influence any of the hematology parameters and clinical chemistry parameters in plasma and serum samples after 28-day repeated administration. No structural abnormality was observed in the histological examination of organs. Whole genome analysis revealed the absence of virulence factors or genes that may transmit antibiotic resistance. In the double-blind study with 60 human participants (aged 18–60 years), consumption of S. salivarius UBSS-01 for 30 days was found to be safe and results were comparable with placebo treatment These findings indicate that S. salivarius UBSS-01 may be safe for human consumption.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"10 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812420","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}
引用次数: 0
Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii 用 Komagataella phaffii 生产的重组人乳铁蛋白对大鼠进行剂量范围毒性研究
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-22 DOI: 10.1177/10915818241247013
Ross Peterson, Robert B. Crawford, Lance K. Blevins, Norbert E. Kaminski, June S. Sass, Bryce Ferraro, Roma Vishwanath-Deutsch, Anthony J. Clark, Carrie-Anne Malinczak
{"title":"Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii","authors":"Ross Peterson, Robert B. Crawford, Lance K. Blevins, Norbert E. Kaminski, June S. Sass, Bryce Ferraro, Roma Vishwanath-Deutsch, Anthony J. Clark, Carrie-Anne Malinczak","doi":"10.1177/10915818241247013","DOIUrl":"https://doi.org/10.1177/10915818241247013","url":null,"abstract":"The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3–6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina’s intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"29 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140804396","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}
引用次数: 0
Recovery Animals in Toxicology Studies: An Innovation and Quality Consortium Perspective on Best Practices With Case Study Examples 恢复毒理学研究中的动物:创新与质量联合会的最佳实践视角及案例研究实例
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-12 DOI: 10.1177/10915818241243350
Smita Salian-Mehta, James D. Smith, Thierry D. Flandre, Amy L. Lambert, Joan H. Lane, Alan H. Stokes, Kathy Orsted, Natalie A. Bratcher-Petersen, Kyathanahalli S. Janardhan, Elizabeth G. Tonkin
{"title":"Recovery Animals in Toxicology Studies: An Innovation and Quality Consortium Perspective on Best Practices With Case Study Examples","authors":"Smita Salian-Mehta, James D. Smith, Thierry D. Flandre, Amy L. Lambert, Joan H. Lane, Alan H. Stokes, Kathy Orsted, Natalie A. Bratcher-Petersen, Kyathanahalli S. Janardhan, Elizabeth G. Tonkin","doi":"10.1177/10915818241243350","DOIUrl":"https://doi.org/10.1177/10915818241243350","url":null,"abstract":"The inclusion of recovery animals in nonclinical safety studies that support clinical trials is undertaken with a wide diversity of approaches even while operating under harmonized regulatory guidance. While empirical evaluation of reversibility may enhance the overall nonclinical risk assessment, there are often overlooked opportunities to reduce recovery animal use by leveraging robust scientific and regulatory information. In the past, there were several attempts to benchmark recovery practices; however, recommendations have not been consistently applied across the pharmaceutical industry. A working group (WG) sponsored by the 3Rs Translational and Predictive Sciences Leadership Group of the IQ Consortium conducted a survey of current industry practice related to the evaluation of reversibility/recovery in repeat dose toxicity studies. Discussion among the WG representatives included member company strategies and case studies that highlight challenges and opportunities for continuous refinements in the use of recovery animals. The case studies presented in this paper demonstrate increasing alignment with the Society of Toxicologic Pathology recommendations (2013) towards (1) excluding recovery phase cohorts by default (include only when scientifically justified), (2) minimizing the number of recovery groups (e.g., control and one dose level), and (3) excluding controls in the recovery cohort by leveraging external and/or dosing phase data. Recovery group exclusion and decisions regarding the timing of reversibility evaluation may be driven by indication, modality, and/or other scientific or strategic factors using a weight of evidence approach. The results and recommendations discussed present opportunities to further decrease animal use without impacting the quality of human risk assessment.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"1 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577692","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}
引用次数: 0
Editor’s Note 编者按
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-04 DOI: 10.1177/10915818241245479
Mary Beth Genter
{"title":"Editor’s Note","authors":"Mary Beth Genter","doi":"10.1177/10915818241245479","DOIUrl":"https://doi.org/10.1177/10915818241245479","url":null,"abstract":"","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"86 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140577623","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}
引用次数: 0
Safety Assessment of Zinc Salts as Used in Cosmetics. 化妆品中使用的锌盐的安全性评估。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-01 Epub Date: 2024-01-27 DOI: 10.1177/10915818241227124
Laura N Scott, Monice Fiume, Jinqiu Zhu, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Bart Heldreth
{"title":"Safety Assessment of Zinc Salts as Used in Cosmetics.","authors":"Laura N Scott, Monice Fiume, Jinqiu Zhu, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Bart Heldreth","doi":"10.1177/10915818241227124","DOIUrl":"10.1177/10915818241227124","url":null,"abstract":"<p><p>The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 inorganic and organometallic zinc salts as used in cosmetic formulations; these salts are specifically of the <sup>2+</sup> (II) oxidation state cation of zinc. These ingredients included in this report have various reported functions in cosmetics, including hair conditioning agents, skin conditioning agents, cosmetic astringents, cosmetic biocides, preservatives, oral care agents, buffering agents, bulking agents, chelating agents, and viscosity increasing agents. The Panel reviewed the relevant data for these ingredients, and concluded that these 27 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"5S-69S"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570305","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}
引用次数: 0
Safety Assessment of Alkane Diols as Used in Cosmetics. 化妆品中使用的烷二醇安全性评估。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-04-01 Epub Date: 2024-01-04 DOI: 10.1177/10915818231224234
Laura N Scott, Monice Fiume, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Bart Heldreth
{"title":"Safety Assessment of Alkane Diols as Used in Cosmetics.","authors":"Laura N Scott, Monice Fiume, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Bart Heldreth","doi":"10.1177/10915818231224234","DOIUrl":"10.1177/10915818231224234","url":null,"abstract":"<p><p>The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 alkane diol ingredients as used in cosmetics. The alkane diols are structurally related to each other as small diols, and most are reported to function in cosmetics as solvents. The Panel reviewed the relevant data for these ingredients, and concluded that seven alkane diols are safe in cosmetics in the present practices of use and concentration described in this safety assessment, but that the available data are insufficient to make a determination of safety for three ingredients, namely 1,4-Butanediol, 2,3-Butanediol, and Octanediol.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"70S-131S"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086791","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}
引用次数: 0
Mutagenicity Assessment of Homologous Series of Methyl Ester Sulphonates (MES) Using the Bacterial Reverse Mutation (Ames) Test. 利用细菌反向突变(Ames)试验评价甲基酯磺酸盐(MES)同源序列的致突变性。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-12-04 DOI: 10.1177/10915818231217041
Yusrabbil Amiyati Yusof, Zafarizal Aldrin Azizul Hasan, Zulina Abd Maurad
{"title":"Mutagenicity Assessment of Homologous Series of Methyl Ester Sulphonates (MES) Using the Bacterial Reverse Mutation (Ames) Test.","authors":"Yusrabbil Amiyati Yusof, Zafarizal Aldrin Azizul Hasan, Zulina Abd Maurad","doi":"10.1177/10915818231217041","DOIUrl":"10.1177/10915818231217041","url":null,"abstract":"<p><p>Methyl ester sulphonate (MES) is an anionic surfactant that is suitable to be used as an active ingredient in household products. Four palm-based MES compounds with various carbon chains, namely C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub> and C<sub>16/18</sub> MES, were assayed by the in vitro bacterial reverse mutation (Ames) test in the <i>Salmonella typhimurium</i> strains TA98, TA100, TA1535, and TA1537 and the <i>Escherichia coli</i> strain WP2 <u>uvrA</u>, with the aim of establishing the safety data of the compounds, specifically their mutagenicity. The test was also carried out on linear alkylbenzene sulphonate (LAS) for comparison. The plate incorporation method was conducted according to the Organization for Economic Cooperation and Development (OECD) Test Guideline 471. All compounds were tested at five analysable non-cytotoxic concentrations, varying from .001 mg/plate to 5 mg/plate, with and without S-9 metabolic activation. All tested concentrations showed no significant increase in the number of revertant colonies compared to revertant colonies of the negative control. The Ames test indicated that each concentration of C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub>, C<sub>16/18</sub> MES, and LAS used in this study induced neither base-pair substitutions nor frame-shift mutations in the <i>S. typhimurium</i> strains TA98, TA100, TA1535, and TA1537 and the <i>E</i>. <i>coli</i> strain WP2 <u>uvrA</u>. The results showed that C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub> and C<sub>16/18</sub> MES have no potential mutagenic properties in the presence and absence of S-9 metabolic activation, similarly to LAS. Therefore, the MES is safe to be used as an alternative to petroleum-based surfactants for household cleaning products.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"157-164"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482318","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}
引用次数: 0
Copper Chaperone Atox1 Protected the Cochlea From Cisplatin by Regulating the Copper Transport Family and Cell Cycle. 铜伴侣阿托x1通过调节铜转运家族和细胞周期保护耳蜗免受顺铂的侵害。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-10-20 DOI: 10.1177/10915818231206665
Xubo Chen, Weiren Xiang, Lihua Li, Kai Xu
{"title":"Copper Chaperone Atox1 Protected the Cochlea From Cisplatin by Regulating the Copper Transport Family and Cell Cycle.","authors":"Xubo Chen, Weiren Xiang, Lihua Li, Kai Xu","doi":"10.1177/10915818231206665","DOIUrl":"10.1177/10915818231206665","url":null,"abstract":"<p><p>Antioxidant 1 copper chaperone (Atox1) may contribute to preventing DDP cochlear damage by regulating copper transport family and cell cycle proteins. A rat model of cochlear damage was developed by placing gelatin sponges treated with DDP in the cochlea. HEI-OC1 cells were treated with 133 μM DDP as a cell model. DDP-induced ototoxicity in rats was confirmed by immunofluorescence (IF) imaging. The damage of DDP to HEI-OC1 cells was assessed by using CCK-8, TUNEL, and flow cytometry. The relationship between Atox1, a member of the copper transport protein family, and the damage to <i>in vivo</i>/<i>vitro</i> models was explored by qRT-PCR, western blot, CCK-8, TUNEL, and flow cytometry. DDP had toxic and other side effects causing cochlear damage and promoted HEI-OC1 cell apoptosis and cell cycle arrest. The over-expression of Atox1 (oe-Atox1) was accomplished by transfecting lentiviral vectors into <i>in vitro</i>/<i>vivo</i> models. We found that oe-Atox1 increased the levels of Atox1, copper transporter 1 (CTR1), and SOD3 in HEI-OC1 cells and decreased the expression levels of ATPase copper transporting α (ATP7A) and ATPase copper transporting β (ATP7B). In addition, the transfection of oe-Atox1 decreased cell apoptosis rate and the number of G2/M stage cells. Similarly, the expression of myosin VI and phalloidin of cochlea cells <i>in vivo</i> decreased. Atox1 ameliorated DDP-induced damage to HEI-OC1 cells or rats' cochlea by regulating the levels of members of the copper transport family.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"134-145"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677417","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}
引用次数: 0
Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Exacerbates Methamphetamine-Induced Activation of Microglia and Neuroinflammation. 髓细胞2缺乏触发受体表达加剧甲基苯丙胺诱导的小胶质细胞活化和神经炎症。
IF 2.2 4区 医学
International Journal of Toxicology Pub Date : 2024-03-01 Epub Date: 2023-11-25 DOI: 10.1177/10915818231216397
Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li
{"title":"Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Exacerbates Methamphetamine-Induced Activation of Microglia and Neuroinflammation.","authors":"Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li","doi":"10.1177/10915818231216397","DOIUrl":"10.1177/10915818231216397","url":null,"abstract":"<p><p>Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to neurotoxicity and drug addiction. Studies have shown that neurotoxicity is strongly associated with METH-induced neuroinflammation, and microglia are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is reported to play a key role in activation of microglia and neuroinflammation. Yet, the molecular mechanisms by which METH causes neuroinflammation and neurotoxicity remain elusive. In the current study, we investigated the role of TREM2 in neuroinflammation induced by METH in BV2 cells and the wild-type (WT) C57BL/6J mice, CX3CR1<sup>GFP/+</sup> transgenic mice, and TREM2 knockout (KO) mice. Postmortem samples from the frontal cortex of humans with a history of METH use were also analyzed to determine the levels of TREM2, TLR4, IBA1, and IL-1β. The expression levels of TREM2, TLR4, IBA1, IL-1β, iNOS, and Arg-1 were then assessed in the BV2 cells and frontal cortex of mice and human METH users. Results revealed that the expression levels of TREM2, TLR4, IBA1, and IL-1β were significantly elevated in METH-using individuals and BV2 cells. Microglia were clearly activated in the frontal cortex of WT C57BL/6 mice and CX3CR1<sup>GFP/+</sup> transgenic mice, and the protein levels of IBA1, TREM2, TLR4, and IL-1β were elevated in the METH-induced mouse models. Moreover, TREM2-KO mice showed further increased microglial activation, neuroinflammation, and excitotoxicity induced by METH. Thus, these findings suggest that TREM2 may be a target for regulating METH-induced neuroinflammation.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"165-176"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434038","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}
引用次数: 0
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