Toxicological Research最新文献

{"title":"Atg5 knockout induces alternative autophagy via the downregulation of Akt expression.","authors":"Hye-Gyo Kim, Myeong-Han Ro, Michael Lee","doi":"10.1007/s43188-023-00191-3","DOIUrl":"10.1007/s43188-023-00191-3","url":null,"abstract":"<p><p>Autophagy play contradictory roles in cellular transformation. We previously found that the knockout (KO) of autophagy-related 5 (Atg5), which is essential for autophagy, leads to the malignant transformation of NIH 3T3 cells. In this study, we explored the mechanism by which autophagy contributes to this malignant transformation using two transformed cell lines, Atg5 KO and Ras-NIH 3T3. Monomeric red fluorescent protein-green fluorescent protein-light chain 3 reporter and Cyto-ID staining revealed that Ras-NIH 3T3 cells exhibited higher basal autophagy activity than NIH 3T3 cells. Additionally, transformed cells, regardless of their Atg5 KO status, were more sensitive to autophagy inhibitors (SBI-0206965, chloroquine, and obatoclax) than the untransformed NIH 3T3 cells, suggesting that the transformed cells are more autophagy-dependent than the normal cells. Loss of Atg5 improved the cell viability and mobility, especially in Ras-NIH 3T3 cells. Furthermore, we discovered that autophagy was alternatively induced in a Rab9-dependent manner in Ras-NIH 3T3 and NIH 3T3/Atg5 KO cells. In particular, Atg5 KO cells showed reduced mTOR-mediated phosphorylation of Akt (pAkt S473), indicating the mTOR-independent occurrence of alternative autophagy in Atg5 KO cells. Therefore, our study provides evidence that alternative autophagy may contribute to tumorigenesis in cells with an impaired Atg5-dependent autophagy pathway.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00191-3.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 4","pages":"637-647"},"PeriodicalIF":1.6,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150170","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":"Endotoxin of <i>Porphyromonas gingivalis</i> amplifies the inflammatory response in hyperglycemia-induced zebrafish through a mechanism involving chitinase-like protein YKL-40 analogs.","authors":"Gizem Gündüz, Merih Beler, İsmail Ünal, Derya Cansız, Ebru Emekli-Alturfan, Kemal Naci Kose","doi":"10.1007/s43188-023-00190-4","DOIUrl":"10.1007/s43188-023-00190-4","url":null,"abstract":"<p><p><i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), a key pathogen in periodontal diseases, is also associated with hyperglycemia-associated systemic diseases, including diabetes mellitus (DM). Gingipains are the most important endotoxins of <i>P. gingivalis,</i> and in vivo studies using gingipains are scarce. Zebrafish (<i>Danio rerio</i>) is a vertebrate with high physiological and genetic homology with humans that has multiple co-orthologs for human genes, including inflammation-related proteins. The aim of our study was to determine the effects of gingipain in a hyperglycemia-induced zebrafish model by evaluating inflammation, oxidant-antioxidant status, and the cholinergic system. Adult zebrafish were grouped into the control group (C), hyperglycemia-induced group subjected to 15 days of overfeeding (OF), gingipain-injected group (GP), and gingipain-injected hyperglycemic group (OF + GP). At the end of 15 days, an oral glucose tolerance test (OGTT) was performed, and fasting blood glucose (FBG) levels were measured. Lipid peroxidation (LPO), nitric oxide (NO), glutathione (GSH), glutathione S-transferase, catalase, acetylcholinesterase (AChE), alkaline phosphatase (ALP), and sialic acid (SA) levels were determined spectrophotometrically in the hepatopancreas. The expression levels of <i>tnf-⍺, il-1β, ins, crp,</i> and the acute phase protein YKL-40 analogs <i>chia.5</i> and <i>chia.6</i> were evaluated by RT‒PCR. After two weeks of overfeeding, significantly increased weight gain, FBG, and OGTT confirmed that the zebrafish were hyperglycemic. Increased oxidative stress, inflammation, and AChE and ALP activities were observed in both the overfeeding and GP groups. Amplification of inflammation and oxidative stress was evident in the OF + GP group through increased expression of crp, <i>il-1β</i>, <i>chia.5,</i> and <i>chia.6</i> and increased LPO and NO levels. Our results support the role of gingipains in the increased inflammatory response in hyperglycemia-associated diseases.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 4","pages":"625-636"},"PeriodicalIF":1.6,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152229","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":"Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone-induced toxicities in rats: comparative study with other mitochondrial uncouplers (2,4-dinitrophenol, OPC-163493 and tolcapone).","authors":"Yuki Inoue, Yuko Wada, Makoto Sato, Seiji Sato, Takashi Okamoto, Naohide Kanemoto","doi":"10.1007/s43188-023-00189-x","DOIUrl":"10.1007/s43188-023-00189-x","url":null,"abstract":"<p><p>FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) is known to inhibit oxidative phosphorylation as a protonophore, dissipating the proton gradient across the inner mitochondrial membrane. To understand the toxicity of FCCP, 3-day, 2- and 4-week repeated oral dose studies were performed in male rats. In the 3-day and 2-week repeated dose toxicity studies, observations included salivation, increased body temperature, and dead and moribund animals. Increased liver weight was observed in conjunction with hydropic degeneration and centrilobular necrosis of hepatocytes. In addition, pathological changes were observed in the pancreas, testis, epididymal duct, stomach and parotid gland. Electron microscopic examination revealed mitochondrial pleomorphism in the hepatocytes. Swelling of mitochondria was observed in the alpha cells and beta cells of the pancreas. Dilatation of rough endoplasmic reticulum, Golgi bodies and loss of secretory granules were also noted in the beta cells of the pancreas. FCCP was also compared with three other mUncouplers (DNP, OPC-163493 and tolcapone) with regard to in vitro mitochondrial uncoupling (mUncoupling) activities. FCCP produced the peak ΔOCR (oxygen consumption rate) at the lowest concentration (0.4 μM), followed by OPC-163493, tolcapone, and DNP, based on peak values in ascending order of concentration (2.5, 10, and 50 μM, respectively). Considering the relationship between the mUncoupling activity and toxicity profile of the four mUncouplers, there is no parallel relationship between the in vitro mUncoupling activity and the degree of in vivo toxicity. These findings may contribute to the efficient development of new mitochondrial uncoupler candidates.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00189-x.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 4","pages":"611-623"},"PeriodicalIF":1.6,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177114","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":"<i>Pelargonium sidoides</i> extract mediates nephrotoxicity through mitochondrial malfunction and cytoskeleton destabilization.","authors":"Ju Young Lee, JuKyung Lee, Sung Ho Lee, Jeong Ho Hwang, Han Na Suh","doi":"10.1007/s43188-023-00186-0","DOIUrl":"10.1007/s43188-023-00186-0","url":null,"abstract":"<p><p>We investigated the cytotoxic effect of <i>Pelargonium sidoides</i> extract on Madin-Darby canine kidney (MDCK) cells. <i>P. sidoides</i> extract decreased the cell viability in a dose dependent manner (> 0.2%). The extract of <i>P. sidoides</i> decreased the mitochondrial action potential, increased the number of reactive oxygen species (ROS) inside the cell, and caused nicotinamide adenine dinucleotide hydride (NADH) to be released, all of which are signs of mitochondrial dysfunction. The results of unbiased mRNA sequencing showed that 0.3% <i>P. sidoides</i> extract upregulates the apoptosis-related gene (<i>BBC3</i>). This finding was supported by immunoblot analysis of apoptosis signal pathways, which included Bcl-2, Bax, cytochrome C (CytC), cleaved caspase 3 (CC3), cleaved caspase 7 (CC7), cleaved caspase 9 (CC9) and cleaved PARP (CP). It is interesting to note that the elevated levels of Bax, CytC, CC3, CC7, and CC9, as well as CP, were suppressed by N-acetyl-L-cysteine (NAC) pretreatment, which points to ROS-mediated apoptosis. The small GTPases, RhoA, and Rac1/cdc42-GTP-bound active form were all lowered when <i>P. sidoide</i>s extract was used. Also, RhoA-related cytoskeleton signals (ROCK, p-LIMK1/2, p-cofilin) and Rac1/cdc42-related signals (N-WASP, WAVE-2) were inhibited by <i>P. sidoides</i> extract. NAC or RhoA/Rac1/cdc42 activator pretreatment reduced <i>P. sidoides</i> extract-induced actin destabilization. In this work, <i>P. sidoides</i> extract promotes apoptosis by causing mitochondrial dysfunction and cytoskeleton disassembly.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 4","pages":"601-609"},"PeriodicalIF":1.6,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152228","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":"Characterisation of changes in global genes expression in the lung of ICR mice in response to the inflammation and fibrosis induced by polystyrene nanoplastics inhalation.","authors":"You Jeong Jin,&nbsp;Ji Eun Kim,&nbsp;Yu Jeong Roh,&nbsp;Hee Jin Song,&nbsp;Ayun Seol,&nbsp;Jumin Park,&nbsp;Yong Lim,&nbsp;Sungbaek Seo,&nbsp;Dae Youn Hwang","doi":"10.1007/s43188-023-00188-y","DOIUrl":"10.1007/s43188-023-00188-y","url":null,"abstract":"<p><p>This study characterised the changes in global gene expression in the lung of ICR mice in response to the inflammation and fibrosis induced by the inhalation of 0.5 μm polystyrene (PS)-nanoplastics (NPs) at various concentrations (4, 8, and 16 μg/mL) for 2 weeks. The total RNA extracted from the lung tissue of NPs-inhaled mice was hybridised into oligonucleotide microarrays. Significant upregulation was detected in several inflammatory responses, including the number of immune cells in bronchoalveolar lavage fluid (BALF), the expression level of inflammatory cytokines, mucin secretion, and histopathological changes, while they accumulated average of 13.38 ± 1.0 μg/g in the lungs of the inhaled ICR mice. Similar responses were observed regarding the levels of fibrosis-related factors in the NPs-inhaled lung of ICR mice, such as pulmonary parenchymal area, expression of pro-fibrotic marker genes, and TGF-β1 downstream signalling without any significant hepatotoxicity and nephrotoxicity. In microarray analyses, 60 genes were upregulated, and 55 genes were downregulated in the lung of ICR mice during inflammation and fibrosis induced by NPs inhalation compared to the Vehicle-inhaled mice. Among these genes, many were categorised into several ontology categories, including the anatomical structure, binding, membrane, and metabolic process. Furthermore, the major genes in the upregulated categories included Igkv14-126000, Egr1, Scel, Lamb3, and Upk3b. In contrast, the major genes in the down-regulated categories were Olfr417, Olfr519, Rps16, Rap2b, and Vmn1r193. These results suggest several gene functional groups and individual genes as specific biomarkers respond to inflammation and fibrosis induced by PS-NPs inhalation in ICR mice.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00188-y.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":" ","pages":"1-25"},"PeriodicalIF":2.3,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9714952","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":"Impacts of PAH accumulation on reproductive hormones, indices of oxidative stress and BPDE-albumin adduct in women with recurrent pregnancy loss.","authors":"Amany El-Sikaily,&nbsp;Mohamed Helal,&nbsp;Augusta Chinyere Nsonwu-Anyanwu,&nbsp;Hossam Azab,&nbsp;Neveen Abd ElMoneim,&nbsp;Eman Othman Salem Farahat,&nbsp;Aziza Saad","doi":"10.1007/s43188-023-00181-5","DOIUrl":"10.1007/s43188-023-00181-5","url":null,"abstract":"<p><p>Chronic exposure to Poly aromatic hydrocarbons (PAHs) may be associated with adverse pregnancy outcomes. Disruption of hormonal and redox balance by toxic PAH metabolites may interfere with successful pregnancy leading to miscarriage. The association of exposure to PAH contaminated mussel via the dietary route with perturbations in reproductive hormones, biomarkers of oxidative stress, and PAH metabolites were assessed in women with recurrent pregnancy loss (RPL). Furthermore, an analysis of the concentration of PAHs in environmentally relevant bivalve animals was performed to preliminary get insights into the levels of these pollutants in the environment. Seventy-six women (20-35 years) were categorized into 18 fertile women without RPL (control), and Groups I, II, and III comprising 24, 18, and 16 women with RPL (2, 3, and > 3 abortions respectively) were studied. Whole blood samples were collected for the estimation of malondialdehyde (MDA), catalase, reduced glutathione (GSH), glutathione-S-transferase (GST), progesterone (P4), follicle-stimulating hormone (FSH), benzo[a]pyren-7,8-dihydrodiol-9,10-epoxide-albumin adduct (BPDE-albumin) and urine for α-naphthol and β-naphthol. Two species of mussel <i>Donax trunculus</i> and <i>Andar aduloii</i> samples were collected for the estimation of 16 priority PAHs. The concentration of PAHs exceeding the maximum limits was observed in the two species of mussels studied. Higher levels of BPDE-albumin, MDA, GST, α and β-naphthol and lower GSH, catalase, FSH, and P4 were observed in women with RPL (Groups I-III) compared to controls (<i>p</i> =  < 0.001). Negative associations were observed between BPDE-albumin and catalase (r = - 0.276, <i>p</i> = 0.036), and GSH (r = - 0.331, <i>p</i> = - 0.011) only in women with RPL. Collectively, our findings indicate a possible association of chronic PAH accumulation with recurrent pregnancy loss in women.</p><p><strong>Graphical abstract: </strong>High PAH exposure in pregnant women is associated with 10-epoxide-albumin adduct formation and high MDA levels in their sera. On the other hand, PAH exposure in those women led to a decrease in their GSH, catalase, P4, and FSH sera levels. These findings indicate that PAH exposure can exert different physiological effects in pregnant women leading to a high level of abortion in those women.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"517-531"},"PeriodicalIF":2.3,"publicationDate":"2023-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743939","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":"Recent insights into autophagy and metals/nanoparticles exposure.","authors":"Qiong Li, Yajing Feng, Ruike Wang, Rundong Liu, Yue Ba, Hui Huang","doi":"10.1007/s43188-023-00184-2","DOIUrl":"10.1007/s43188-023-00184-2","url":null,"abstract":"<p><p>Some anthropogenic pollutants, such as heavy metals and nanoparticles (NPs), are widely distributed and a major threat to environmental safety and public health. In particular, lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg) have systemic toxicity even at extremely low concentrations, so they are listed as priority metals in relation to their significant public health burden. Aluminum (Al) is also toxic to multiple organs and is linked to Alzheimer's disease. As the utilization of many metal nanoparticles (MNPs) gradually gain traction in industrial and medical applications, they are increasingly being investigated to address potential toxicity by impairing certain biological barriers. The dominant toxic mechanism of these metals and MNPs is the induction of oxidative stress, which subsequently triggers lipid peroxidation, protein modification, and DNA damage. Notably, a growing body of research has revealed the linkage between dysregulated autophagy and some diseases, including neurodegenerative diseases and cancers. Among them, some metals or metal mixtures can act as environmental stimuli and disturb basal autophagic activity, which has an underlying adverse health effect. Some studies also revealed that specific autophagy inhibitors or activators could modify the abnormal autophagic flux attributed to continuous exposure to metals. In this review, we have gathered recent data about the contribution of the autophagy/mitophagy mediated toxic effects and focused on the involvement of some key regulatory factors of autophagic signaling during exposure to selected metals, metal mixtures, as well as MNPs in the real world. Besides this, we summarized the potential significance of interactions between autophagy and excessive reactive oxygen species (ROS)-mediated oxidative damage in the regulation of cell survival response to metals/NPs. A critical view is given on the application of autophagy activators/inhibitors to modulate the systematic toxicity of various metals/MNPs.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"355-372"},"PeriodicalIF":1.6,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743941","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":"Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers.","authors":"Harrison Ozoani, Anthonet N Ezejiofor, Kenneth O Okolo, Chinna N Orish, Ana Cirovic, Aleksandar Cirovic, Orish E Orisakwe","doi":"10.1007/s43188-023-00187-z","DOIUrl":"10.1007/s43188-023-00187-z","url":null,"abstract":"<p><p>Heavy metals (HMs) such as cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) are highly toxic elements. They are often found together in nature as a heavy metal mixture (HMM) and are known to contribute to subfertility/infertility as environmental pollutants. This study aims to evaluate the potential benefits of treating HMM-induced testicular pathophysiology with zinc (Zn) and/or selenium (Se). Six-week-old male Sprague Dawley rats were grouped into 5 (n = 7). The control group received deionized water, while the other groups were treated with PbCl₂ (20 mg kg^-1), CdCl₂ (1.61 mg kg^-1), HgCl₂ (0.40 mg kg^-1), and Na₂AsO₃ (10 mg kg^-1) in deionized water for 60 days. Additionally, groups III to V received Zn, Se, and Zn/Se, respectively, for 60 days. The study evaluated testis weight, metal accumulation, sperm analysis, FSH, LH, testosterone, prolactin, oxidative stress, antioxidants, pro-inflammatory and apoptotic markers, and presented structural changes in the testis as micrographs. HMM caused a significant increase in testis weight, metal accumulation, prolactin, oxidative stress, and pro-inflammatory and apoptotic markers, while significantly decreasing semen analysis, FSH, LH, and testosterone. Histology showed decreased spermatogenesis and spermiogenesis, as evidenced by the structure of the germ cells and spermatids. However, Zn, Se, or both ameliorated and reversed some of the observed damages. This study provides further evidence for the mitigative potential of Zn, Se, or both in reversing the damage inflicted by HMM in the testis, and as a countermeasure towards improving HM-induced decrease in public health fecundity.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"497-515"},"PeriodicalIF":1.6,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737594","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":"Defining the reactivity of nanoparticles to peptides through direct peptide reactivity assay (DPRA) using a high pressure liquid chromatography system with a diode array detector.","authors":"Eun-Nam Kim, Jung-Ah Seo, Bae-Hwan Kim, Gil-Saeng Jeong","doi":"10.1007/s43188-022-00166-w","DOIUrl":"10.1007/s43188-022-00166-w","url":null,"abstract":"<p><p>The possibility of inducing skin sensitization reactions following exposure to various chemicals can lead to skin diseases, and the evaluation of skin sensitivity to such substances is very important. However, as animal tests for skin sensitization are prohibited, the OECD Test Guideline 442 C was designated as part of an alternative testing method. Therefore, in this study, the reactivity of cysteine and lysine peptides to nanoparticle substrates was identified through HPLC-DAD analysis according to the skin sensitization animal replacement test method specified in the OECD Test Guideline 442 C. In this study, all criteria for skin sensitization experiments specified in OECD Test Guideline 442 C were satisfied. As a result of analyzing the disappearance rates of cysteine and lysine peptides for the five types of nanoparticle substrates (TiO₂, CeO₂, Co₃O₄, NiO, and Fe₂O₃) using the established analytical method, all were identified as positive. Therefore, our findings suggest that basic data from this technique can contribute to skin sensitization studies by providing the depletion percentage of cysteine and lysine peptides for nanoparticle materials that have not yet been tested for skin sensitization.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"485-495"},"PeriodicalIF":1.6,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743937","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":"Comparison of structural characteristics and molecular markers of rabbit skin, pig skin, and reconstructed human epidermis for an ex vivo human skin model.","authors":"Chanyang Uhm,&nbsp;Haengdueng Jeong,&nbsp;Su Hyon Lee,&nbsp;Jae Sung Hwang,&nbsp;Kyung-Min Lim,&nbsp;Ki Taek Nam","doi":"10.1007/s43188-023-00185-1","DOIUrl":"10.1007/s43188-023-00185-1","url":null,"abstract":"<p><p>The Organization for Economic Co-operation and Development approved a reconstructed human epidermis (RHE) model for <i>in vitro</i> skin irritation and corrosion tests as an alternative to animal testing for cosmetics, which has been banned in the European Union since 2013. However, RHE models have several limitations, such as high manufacturing costs, a loose skin barrier, and inability to simulate all cellular and non-cellular components of the human epidermis. Therefore, new alternative skin models are needed. Ex vivo skin models have been suggested as promising tools. Here, we investigated the structural similarities in the epidermis of pig and rabbit skin, a commercial RHE model (Keraskin), and human skin. To compare the structural similarity, the thickness of each epidermal layer was compared using molecular markers. Among the candidate human skin surrogates, the epidermal thickness of the pig skin was the most similar to that of human skin, followed by rabbit skin and Keraskin. Keraskin showed thicker cornified and granular layers than human skin, while rabbit skin displayed thinner layers. Moreover, the proliferation indices of Keraskin and rabbit skin were higher than those of human skin, whereas the proliferation index of the pig skin was similar to that of human skin. Some or none of the human skin barrier proteins FLG, CLDN1, and CDH1 were expressed in pig and rabbit skin, whereas all human proteins were expressed in Keraskin. Collectively, we propose ex vivo pig skin as the most suitable model for skin irritation testing because of its similarity to human skin.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-023-00185-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"39 3","pages":"477-484"},"PeriodicalIF":2.3,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749085","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}