Toxicological Research最新文献

{"title":"Blood vessel remodeling in the cerebral cortex induced by binge alcohol intake in mice.","authors":"Hiroshi Hasegawa, Toshiya Tanaka, Mari Kondo, Koji Teramoto, Kei Nakayama, Gi-Wook Hwang","doi":"10.1007/s43188-022-00164-y","DOIUrl":"10.1007/s43188-022-00164-y","url":null,"abstract":"<p><p>Ethanol is toxic to the brain and causes various neurological disorders. Although ethanol can directly exert toxicity on neurons, it also acts on other cell types in the central nervous system. Blood vessel endothelial cells interact with, and are affected by blood ethanol. However, the effects of ethanol on the vascular structures of the brain have not been well documented. In this study, we examined the effects of binge levels of ethanol on brain vasculature. Immunostaining analysis indicated structural alterations of blood vessels in the cerebral cortex, which became more tortuous than those in the control mice after ethanol administration. The interaction between the blood vessels and astrocytes decreased, especially in the upper layers of the cerebral cortex. Messenger RNA expression analysis revealed a unique downregulation of <i>Vegfa</i> mRNA encoding vascular endothelial growth factor (VEGF)-A among VEGF, angiopoietin, endothelin family angiogenic and blood vessel remodeling factors. The expression of three proteoglycan core proteins, glypican-5, neurocan, and serglycin, was also altered after ethanol administration. Thus, binge levels of ethanol affect the expression of VEGF-A and blood vessel-supporting proteoglycans, resulting in changes in the vascular structure of the cerebral cortex.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00164-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"169-177"},"PeriodicalIF":2.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696114","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":"Mitochondrial dynamics when mitochondrial toxic chemicals exposed in 3D cultured mouse embryonic stem cell.","authors":"Changhwan Ahn, SunHwa Jeong, Eui-Bae Jeung","doi":"10.1007/s43188-022-00161-1","DOIUrl":"10.1007/s43188-022-00161-1","url":null,"abstract":"<p><p>Mitochondria need to use considerable energy for the intracellular organelles that produce ATP. They are abundant in the cells of organs, such as muscles, liver, and kidneys. The heart, which requires a lot of energy, is also rich in mitochondria. Mitochondrial damage can induce cell death. Doxorubicin, acetaminophen, valproic acid, amiodarone, and hydroxytamoxifen are representative substances that induce mitochondrial damage. On the other hand, the effects of this substance on the progress of cardiomyocyte-differentiating stem cells have not been investigated. Therefore, a 3D cultured embryonic body toxicity test was performed. The results confirmed that the cytotoxic effects on cardiomyocytes were due to mitochondrial damage in the stage of cardiomyocyte differentiation. After drug treatment, the cells were raised in the embryoid body state for four days to obtain the ID₅₀ values, and the levels of mRNA expression associated with the mitochondrial complex were examined. The mitochondrial DNA copy numbers were also compared to prove that the substance affects the number of mitochondria in EB-state cardiomyocytes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00161-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"239-249"},"PeriodicalIF":2.3,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247911","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":"Analytical method development and dermal absorption of 2-amino-5-nitrophenol (2A5NP), a hair dye ingredient under oxidative condition.","authors":"Yu Jin Kim, Hyang Yeon Kim, Jung Dae Lee, Hong Yoon Kim, Jueng Eun Im, Kyu-Bong Kim","doi":"10.1007/s43188-022-00159-9","DOIUrl":"10.1007/s43188-022-00159-9","url":null,"abstract":"<p><p>Although 2-amino-5-nitrophenol (2A5NP) is one of the ingredients of hair dye, there has been no information on the dermal absorption rate of 2A5NP. 2A5NP is managed at less than 1.5% in Korea and Japan. In this study, analytical methods were developed and validated using high-performance liquid chromatography (HPLC) in various matrices of wash, swab, stratum corneum (SC), skin (dermis + epidermis), and receptor fluid (RF). Validation results were acceptable based on Korea Ministry of Food and Drug Safety (MFDS) guideline. The HPLC analysis showed a good linearity (r² = 0.9992-0.9999), a high accuracy (93.1-110.2%), and a good precision (1.1-8.1%) in accordance with the validation guideline. Franz diffusion cell was used to determine dermal absorption of 2A5NP using mini pig skin. 2A5NP (1.5%) was applied to skin at 10 μl/cm². For certain cosmetic ingredients such as hair dye with short exposure time, an interim wash step (after 30 min) was added during the study. After application for 30 min and 24 h, skin was wiped off with swab and SC was collected using tape stripping. RF was sampled at 0, 1, 2, 4, 8, 12, and 24 h. Total dermal absorption rate of 2A5NP (1.5%) was determined to be 13.6 ± 2.9%.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"231-238"},"PeriodicalIF":2.3,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242847","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":"Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice.","authors":"Ishita Seal, Sidhanta Sil, Abhijit Das, Souvik Roy","doi":"10.1007/s43188-022-00158-w","DOIUrl":"10.1007/s43188-022-00158-w","url":null,"abstract":"<p><p>Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD₅₀ of the complex at 500 mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400 mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200 mg/kg group. In the histopathological analysis, the 50, 100, and 200 mg/kg groups were not associated with any toxicological alterations, whereas the 400 mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200 mg/kg without any toxicological and genotoxic potential.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"213-229"},"PeriodicalIF":2.3,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242846","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":"Integrated transcriptomic analysis of liver and kidney after 28 days of thioacetamide treatment in rats.","authors":"Hyoung-Yun Han, Se-Myo Park, Je-Won Ko, Jung-Hwa Oh, Sang Kyum Kim, Tae-Won Kim","doi":"10.1007/s43188-022-00156-y","DOIUrl":"10.1007/s43188-022-00156-y","url":null,"abstract":"<p><p>Thioacetamide (TAA) was developed as a pesticide; however, it was soon found to cause hepatic and renal toxicity. To evaluate target organ interactions during hepatotoxicity, we compared gene expression profiles in the liver and kidney after TAA treatment. Sprague-Dawley rats were treated daily with oral TAA and then sacrificed, and their tissues were evaluated for acute toxicity (30 and 100 mg/kg bw/day), 7-day (15 and 50 mg/kg bw/day), and 4-week repeated-dose toxicity (10 and 30 mg/kg). After the 4-week repeated toxicity study, total RNA was extracted from the liver and kidneys, and microarray analysis was performed. Differentially expressed genes were selected based on fold change and significance, and gene functions were analyzed using ingenuity pathway analysis. Microarray analysis showed that significantly regulated genes were involved in liver hyperplasia, renal tubule injury, and kidney failure in the TAA-treated group. Commonly regulated genes in the liver or kidney were associated with xenobiotic metabolism, lipid metabolism, and oxidative stress. We revealed changes in the molecular pathways of the target organs in response to TAA and provided information on candidate genes that can indicate TAA-induced toxicity. These results may help elucidate the underlying mechanisms of target organ interactions during TAA-induced hepatotoxicity.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00156-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"201-211"},"PeriodicalIF":2.3,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242848","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":"The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats.","authors":"Yong-Soon Kim, Eun-Sang Cho, Chan-Hyuck Park, Hyo-Geun Cha","doi":"10.1007/s43188-022-00162-0","DOIUrl":"10.1007/s43188-022-00162-0","url":null,"abstract":"<p><p>Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6 h a day, 5 days per week) at target concentrations of 45, 90, and 180 mg/m³. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18 mg/m³, 90.69 ± 7.30 mg/m³, and 183.87 ± 15.21 mg/m³, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ± 0.07 μm, 1.47 ± 0.18 μm, and 1.68 ± 0.16 μm, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45 mg/m³.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"157-167"},"PeriodicalIF":2.3,"publicationDate":"2022-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194684","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":"ATF4-activated parkin induction contributes to deferasirox-mediated cytoprotection in Parkinson's disease.","authors":"Sangwoo Ham, Ji Hun Kim, Heejeong Kim, Jeong-Yong Shin, Yunjong Lee","doi":"10.1007/s43188-022-00157-x","DOIUrl":"10.1007/s43188-022-00157-x","url":null,"abstract":"<p><p>The E3 ubiquitin ligase parkin plays neuroprotective functions in the brain and the deficits of parkin's ligase function in Parkinson's disease (PD) is associated with reduced survival of dopaminergic neurons. Thus, compounds enhancing parkin expression have been developed as potential neuroprotective agents that prevent ongoing neurodegeneration in PD environments. Besides, iron chelators have been shown to have neuroprotective effects in diverse neurological disorders including PD. Although repression of iron accumulation and oxidative stress in brains has been implicated in their marked neuroprotective potential, molecular mechanisms of iron chelator's neuroprotective function are largely unexplored. Here, we show that the iron chelator deferasirox provides cytoprotection against oxidative stress through enhancing parkin expression under basal conditions. Parkin expression is required for cytoprotection against oxidative stress in SH-SY5Y cells with deferasirox treatment as confirmed by abolished deferasirox's cytoprotective effect after parkin knockdown by shRNA. Similar to the previously reported parkin inducing compound diaminodiphenyl sulfone, deferasirox-mediated parkin expression was induced by activation of the PERK-ATF4 pathway, which is associated with and stimulated by mild endoplasmic reticulum stress. The translational potential of deferasirox for PD treatment was further evaluated in cultured mouse dopaminergic neurons. There was a robust ATF4 activation and parkin expression in response to deferasirox treatment in dopaminergic neurons under basal conditions. Consequently, the enhanced parkin expression by deferasirox provided substantial neuroprotection against 6-hydroxydopamine-induced oxidative stress. Taken together, our study results revealed a novel mechanism through which an iron chelator, deferasirox induces neuroprotection. Since parkin function in the brain is compromised in PD and during aging, maintenance of parkin expression through the iron chelator treatment could be beneficial by increasing dopaminergic neuronal survival.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"191-199"},"PeriodicalIF":2.3,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247913","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":"Saline extract of <i>Portulaca elatior</i> leaves with photoprotective and antioxidant activities does not show acute oral and dermal toxicity in mice.","authors":"Suéllen Pedrosa da Silva, Clarice Barbosa Lucena da Costa, Anderson Felipe Soares de Freitas, José Dayvid Ferreira da Silva, Wêndeo Kennedy Costa, Wênio Sandoval Filho Lima da Silva, Janaina Carla Barbosa Machado, Sandra Maria Souza da Silva, Magda Rhayanny Assunção Ferreira, Luiz Alberto Lira Soares, Jacinto da Costa Silva Neto, Márcia Vanusa da Silva, Alisson Macário de Oliveira, Patrícia Maria Guedes Paiva, Thiago Henrique Napoleão","doi":"10.1007/s43188-022-00160-2","DOIUrl":"10.1007/s43188-022-00160-2","url":null,"abstract":"<p><p>The present study aimed to evaluate saline extracts from the leaves (LE) and stem (SE) of <i>Portulaca elatior</i> in relation to their phytochemical composition and photoprotective and antioxidant effects, as well as to evaluate the toxicity of the leaf extract. The extracts were characterized for protein concentration and phenol and flavonoid contents, as well as for thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) profiles. Total antioxidant capacity and DPPH and ABTS⁺ scavenging activities were determined. In the photoprotective activity assay, the sun protection factor (SPF) was calculated. The toxicity evaluation of LE included in vitro hemolytic assay and in vivo oral and dermal acute toxicity assays in Swiss mice. LE showed the highest protein, phenol, and flavonoid (8.79 mg/mL, 323.46 mg GAE/g, and 101.96 QE/g, respectively). TLC revealed the presence of flavonoids, reducing sugars, terpenes, and steroids in both extracts. In HPLC profiles, LE contained flavonoids, while SE contained flavonoids and ellagic tannins. The antioxidant activity assays showed the lowest IC₅₀ values ​(34.15-413.3 µg/mL) for LE, which presented relevant SPF (> 6) at 50 and 100 µg/mL. LE demonstrated low hemolytic capacity, and no signs of intoxication were observed in mice treated orally or topically at 1000 mg/kg. However, at 2000 mg/kg, an increase in the mean corpuscular volume of erythrocytes and a reduction in lymphocytes were observed; animals treated topically with 2000 mg/kg displayed scratching behavior during the first hour of observation and showed edema and erythema that regressed after six days. In conclusion, LE did not present acute oral or dermal toxicity in Swiss mice at a dose of 1000 mg/kg and showed slight toxicity in animals treated with 2000 mg/kg.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00160-2.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 2","pages":"179-190"},"PeriodicalIF":2.3,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9242849","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":"Lipid hydroperoxide-derived insulin resistance and its inhibition by pyridoxamine in skeletal muscle cells.","authors":"Seon Hwa Lee, Mizuki Tsutsui, Atsushi Matsunaga, Tomoyuki Oe","doi":"10.1007/s43188-022-00155-z","DOIUrl":"10.1007/s43188-022-00155-z","url":null,"abstract":"<p><p>Oxidative stress is strongly associated with the onset and/or progression of diabetes. Under conditions of oxidative stress, lipid hydroperoxides are decomposed to reactive aldehydes that have been reported to induce insulin resistance by modifying proteins involved in insulin signaling. Pyridoxamine (PM) can inhibit the formation of advanced glycation/lipoxidation end products by scavenging reactive carbonyl species. Thus, PM has emerged as a promising drug candidate for various chronic conditions, including diabetic complications. In this study, L6 skeletal muscle cells were treated with 4-oxo-2(<i>E</i>)-nonenal (ONE), one of the most abundant and reactive lipid-derived aldehydes. Cellular insulin resistance was assessed by measuring insulin-stimulated glucose uptake using 2-deoxyglucose. ONE induced a time- and dose-dependent decrease in glucose uptake. Liquid chromatography/electrospray ionization-mass spectrometry analysis of the reaction between ONE and insulin receptor substrate 1 (IRS1) lysate identified multiple modifications that could disturb the interaction between IRS1 and activated IR, leading to insulin resistance. Pretreatment of the cells with PM restored the ONE-induced decrease in glucose uptake. Concomitantly, the formation of PM-ONE adducts in cell culture medium was increased in a PM-dose dependent manner. PM can therefore prevent lipid hydroperoxide-derived insulin resistance by quenching ONE.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-022-00155-z.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"147-156"},"PeriodicalIF":2.3,"publicationDate":"2022-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10696111","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":"Anti-inflammatory effects of <i>Athyrium yokoscense</i> extract via inhibition of the Erk1/2 and NF-κB pathways in bisphenol A-stimulated A549 cells.","authors":"Jung-Kyu Lee, Won Seok Choi, Jin Yong Song, Oh Seong Kwon, Yeon Jin Lee, Jong Seok Lee, Sarah Lee, Se Rin Choi, Choong Hwan Lee, Ji-Yun Lee","doi":"10.1007/s43188-022-00154-0","DOIUrl":"10.1007/s43188-022-00154-0","url":null,"abstract":"<p><p>Bisphenol A is an environmental endocrine disruptor that has similar functions to estrogen in humans. However, few studies have investigated pulmonary inflammation induced by BPA, and the effect of <i>Athyrium yokoscense</i> extract on this inflammatory response is unknown. In this study, we investigated this effect in A549 human alveolar epithelial cells. BPA at concentrations higher than 100 µM were cytotoxic to A549 cells at 24 and 48 h after treatment; however, AYE (100 µg/mL) had a protective effect against BPA-induced cytotoxicity. AYE also inhibited the generation of intracellular reactive oxygen species, expressions of cyclooxygenase-2 and extracellular signal-regulated kinase1/2 proteins, activities of phospholipase A₂, COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells, and proinflammatory mediators including prostaglandin E₂, tumor necrosis factor-α, and interleukin-6 induced by BPA in A549 cells. This study demonstrated that BPA, which induces chronic lung disease, causes oxidative stress and inflammatory response in lung epithelial cell line, and found that AYE reduces BPA-induced oxidative stress and inflammatory response by down-regulating the Erk1/2 and NF-κB pathways.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 1","pages":"135-146"},"PeriodicalIF":1.6,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194686","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}