Toxicology Reports最新文献

{"title":"Screening of bioactive components in Ferula assafo dried oleo-gum resin and assessment of its protective function against cadmium-induced oxidative damage, genotoxicity, and cytotoxicity in rats","authors":"Hagar E. Mohammed ,&nbsp;Aziza A. El-Nekeety ,&nbsp;Hanan M. Rashwan ,&nbsp;Sekena H. Abdel-Aziem ,&nbsp;Nabila S. Hassan ,&nbsp;Entesar E. Hassan ,&nbsp;Mosaad A. Abdel-Wahhab","doi":"10.1016/j.toxrep.2024.101853","DOIUrl":"10.1016/j.toxrep.2024.101853","url":null,"abstract":"<div><div>Cadmium (Cd) is among the most ecologically harmful heavy metals. The purpose of this work was to identify the biologically active components in dried oleo-resin-gum of <em>Ferula assafo</em> extract (FAE) and assess their preventive efficacy against oxidative damage caused by Cd in rats. The biologically active components were identified using HPLC and GC-MS. Six groups of female Sprague-Dawley rats were randomly assigned and received oral treatment for two weeks. They consisted of the control group, the groups that got FAE at low or high doses (150 and 250 mg/kg b.w.), the group that received CdCl₂ (2 mg/kg b.w.), and the groups that received CdCl₂ + FAE at the low or high dose. Tissues and blood samples were collected for different assays and pathological examinations. The HPLC detected 11 polyphenol compounds, whereas the GC-MS identified 24 bioactive compounds. The <em>in vivo</em> study revealed that CdCl₂ alone disrupted all biochemical indices, oxidative indicators, cytokines, antioxidant enzymes, pro and anti-apoptotic mRNA gene expression, increased DNA fragmentation percentage, and caused pathological alterations in hepatic and renal sections. FAE plus CdCl₂ therapy considerably improved all indicators and the histological architecture of the kidney and liver, with the higher dose being more effective in improving all of the measured parameters. Therefore, FAE is a promising option for food and pharmaceutical applications to protect against oxidative damage caused by Cd exposure.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101853"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput non-homogenous 3D polycaprolactone scaffold for cancer cell and cancer-associated fibroblast mini-tumors to evaluate drug treatment response","authors":"Atena Malakpour-Permlid ,&nbsp;Manuel Marcos Rodriguez ,&nbsp;Gavrielle R. Untracht ,&nbsp;Peter E. Andersen ,&nbsp;Stina Oredsson ,&nbsp;Anja Boisen ,&nbsp;Kinga Zór","doi":"10.1016/j.toxrep.2024.101863","DOIUrl":"10.1016/j.toxrep.2024.101863","url":null,"abstract":"<div><div>High-throughput screening (HTS) three-dimensional (3D) tumor models are a promising approach for cancer drug discovery, as they more accurately replicate <em>in vivo</em> cell behavior than two-dimensional (2D) models. However, assessing and comparing current 3D models for drug efficacy remains essential, given the significant influence of cellular conditions on treatment response. To develop <em>in vivo</em> mimicking 3D models, we evaluated two HTS 3D models established in 96-well plates with 3D polycaprolactone (PCL) scaffolds fabricated using two distinct methods, resulting in scaffolds with either homogenous or non-homogenous fiber networks. These models, based on human HeLa cervical cancer cells and cancer-associated fibroblasts (CAFs) cultured as mono- or co-cultures within the 3D scaffolds, revealed that anticancer drug paclitaxel (PTX) exhibited consistently higher inhibitory concentration 50 (IC₅₀) in 3D (≥ 1000 nM) compared to 2D (≥ 100 nM), indicating reduced toxicity on cells cultured in 3D. Interestingly, the toxicity of PTX was significantly lower on mini-tumors in non-homogenous 3D (IC₅₀: 600 or 1000 nM) than in homogenous 3D cultures (IC₅₀ exceeding 1000 nM). Microscopic studies revealed that the non-homogenous scaffolds closely resemble the tumor collagen network than their homogeneous counterpart. Both 3D scaffolds offer optimal pore size, facilitating efficient cell infiltration into the depth of 58.1 ± 1.2 µm (homogenous) and 86.4 ± 9.8 µm (non-homogenous) within 3D cultures. Cells cultured in the 3D non-homogenous systems exhibited drug treatment responses closer to <em>in vivo</em> conditions, highlighting the role of scaffold structure and design on cellular response to drug treatment. The PCL-based 3D models provide a robust, tunable, and efficient approach for the HTS of anti-cancer drugs compared to conventional 2D systems.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101863"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-arginine supplement ameliorates dichlorvos-induced systemic inflammatory response and liver dysfunction in male wistar rats","authors":"W.A. Saka ,&nbsp;Y.D. Igbayilola ,&nbsp;H.J. Lawan ,&nbsp;M.B. Zakari ,&nbsp;D.E. Awujoola ,&nbsp;P.O. Olarinde ,&nbsp;V.O. Adegoke","doi":"10.1016/j.toxrep.2024.101846","DOIUrl":"10.1016/j.toxrep.2024.101846","url":null,"abstract":"<div><div>Dichlorvos (DDVP), a frequently used organophosphate insecticide, has been shown to cause systemic inflammation and liver damage via oxidative stress and inflammatory pathways. L-arginine, a semi-essential amino acid, has been shown to protect against oxidative damage and inflammation in a variety of animals. The study's main goal was to raise awareness of Dichlorvos's (DDVP) harmful effects on systemic inflammation and liver function, as well as L-arginine's possible mitigating impact. In order to assess the preventive benefits of L-arginine against induced liver dysfunction and systemic inflammation, liver tissue was selected for this investigation due to its vital role in detoxification and its high susceptibility to harm from toxic chemicals such as Dichlorvos. A total of 40 adult Wistar rats were separated into four groups: control, dichlorvos only, L-arginine only, and dichlorvos plus L-arginine. Dichlorvos was provided orally at a dose of 8 mg/kg body weight, whereas L-arginine was given orally at a dose of 100 mg/kg body weight for six weeks. The study investigated systemic inflammation markers (C-reactive protein, TNF-α, IL-6, and Caspase 3) as well as liver function markers (ALT, AST, ALP, albumin, total protein and gamma glutamyl). The findings revealed that dichlorvos significantly (p &lt; 0.05) enhanced systemic inflammation and decreased (p &lt; 0.05) liver function when compared to the control group. However, L-arginine supplementation greatly improved these effects by significantly (p &lt; 0.05) lowering inflammatory indicators and restoring liver enzyme levels to normal. Histopathological findings validated L-arginine's protective function against dichlorvos-induced liver injury. These data indicate that L-arginine supplement may reduce the negative effects of dichlorvos on systemic inflammation and liver function, providing a possible therapeutic method for controlling organophosphate toxicity.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101846"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gossypol enhances ponatinib's cytotoxicity against human hepatocellular carcinoma cells by involving cell cycle arrest, p-AKT/LC3II/p62, and Bcl2/caspase-3 pathways","authors":"Hadeel H. Elkattan ,&nbsp;Alaa E. Elsisi ,&nbsp;Naglaa M. El-Lakkany","doi":"10.1016/j.toxrep.2024.101856","DOIUrl":"10.1016/j.toxrep.2024.101856","url":null,"abstract":"<div><div>Despite significant breakthroughs in frontline cancer research and chemotherapy for hepatocellular carcinoma (HCC), many of the suggested drugs have high toxic side effects and resistance, limiting their clinical utility. Exploring potential therapeutic targets or novel combinations with fewer side effects is therefore crucial in combating this dreadful disease. The current study aims to use a novel combination of ponatinib and gossypol against the HepG2 cell line. Cell survival, FGF19/FGFR4, apoptotic and autophagic cell death, and synergistic drug interactions were assessed in response to increasing concentrations of ponatinib and/or gossypol treatment. Research revealed that ponatinib (1.25–40 μM) and gossypol (2.5–80 μM) reduced the viability of HepG2 cells in a way that was dependent on both time and dose. Ponatinib's anti-proliferation effectiveness was improved synergistically by gossypol and was associated with a rise in apoptotic cell death, cell cycle blockage during the G0/G1 phase, and suppression of the FGF19/FGFR4 axis. Furthermore, the ponatinib/gossypol combination lowered Bcl-2 and p-Akt while increasing active caspase-3, Beclin-1, p62, and LC3II. This combination, however, had no harm on normal hepatocytes. Overall, gossypol enhanced ponatinib's anticancer effects in HCC cells. Notably, this new combination appears to be potential adjuvant targeted chemotherapy, a discovery that warrants more clinical investigation, in the management of patients with HCC.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101856"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fenofibrate ameliorated atorvastatin and piperine-induced ROS mediated reproductive toxicity in male Wistar rats","authors":"Sanjib Ghosh ,&nbsp;Sweata Sarkar ,&nbsp;Maharaj Biswas","doi":"10.1016/j.toxrep.2024.101861","DOIUrl":"10.1016/j.toxrep.2024.101861","url":null,"abstract":"<div><div>Atorvastatin and fenofibrate are well-known lipid-lowering drugs. Atorvastatin acts by reducing the production of cholesterol through the inhibition of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A reductase) enzyme, whereas fenofibrate is a PPAR-α agonist. Piperine is an alkaloid mostly found in black pepper fruits. The present study was planned to evaluate the activities of atorvastatin, fenofibrate, and piperine on the male reproductive system. A total of 35 male Wistar rats were obtained for the experiment. Rats were randomly divided into 7 groups, each group with 5 rats. The experiment was run for 28 days. Group I rat got normal meals for 28 days; Group II received atorvastatin (08 mg/kg/day); Group III received piperine (10 mg/kg/day); and Group IV received fenofibrate (20 mg/kg/day). Group V received atorvastatin (8 mg/kg/day) and piperine (10 mg/kg/day); Group VI received piperine (10 mg/kg/day) and fenofibrate (20 mg/kg/day). VII received fenofibrate (20 mg/kg bw/day) and atorvastatin (8 mg/kg/day). After sacrifice, serum and testicular cholesterol and testosterone levels assessed by ELISA, ROS generation analysed by using flow cytometry, MDA, SOD, and catalase were measured. Histological, sperm-parameter analysis, and spermatogenic evaluations were also done. Activities of atorvastatin and piperine revealed reproductive toxicity upon treatment. Fenofibrate treatment, along with atorvastatin and piperine, showed protective effects. In conclusion, atorvastatin and piperine affected reproductive potential, whereas fenofibrate might have protective efficacy against atorvastatin and piperine-induced reproductive toxicity.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101861"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of dietary acrylamide on kidney and liver health: Molecular mechanisms and pharmacological implications","authors":"Mohammed Nazish Quasmi,&nbsp;Dinesh Kumar,&nbsp;Ashok Jangra","doi":"10.1016/j.toxrep.2024.101859","DOIUrl":"10.1016/j.toxrep.2024.101859","url":null,"abstract":"<div><div>Acrylamide (AA) has raised concerns throughout the world in recent years because of its potential negative effects on human health. Numerous researches on humans and animals have connected a high dietary exposure to AA to a possible risk of cancer. Additionally, higher consumption of acrylamide has also been associated with dysfunctioning of various organ systems from nervous system to the reproductive system. Acrylamide is primarily metabolised into the glycidamide inside the body which gets accumulated in different tissues including kidney and liver, and chronic exposure to this can lead to the nephrotoxicity and hepatotoxicity through different molecular mechanisms. This review summarizes the various sources, formation and metabolism of the dietary acrylamide along with the different molecular mechanisms such as oxidative stress, inflammation, DNA damage, autophagy, mitochondrial dysfunction and morphological changes in nephron and hepatocytes through which acrylamide exerts its deleterious effect on kidney and liver causing nephrotoxicity and hepatotoxicity. This review summarizes various animal and cellular studies that demonstrate AA-induced nephrotoxicity and hepatotoxicity. Lastly, the article emphasizes on underlying protective molecular mechanisms of various pharmacological interventions against acrylamide induced hepatotoxicity and nephrotoxicity</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101859"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-10 levels in azithromycin-induced cardiac damage and the protective role of combined selenium and vitamin E treatment","authors":"Heba Hussein Rohym ,&nbsp;Mohamed S. Hemeda ,&nbsp;Almoatazbellah Mahmoud Elsayed ,&nbsp;Mayada Saad Farrag ,&nbsp;Heba A. Elsayed ,&nbsp;Amgad A. Ezzat ,&nbsp;Mohamed A. Ibrahim ,&nbsp;Mohammed Makloph","doi":"10.1016/j.toxrep.2024.101860","DOIUrl":"10.1016/j.toxrep.2024.101860","url":null,"abstract":"<div><div>Azithromycin is a broad-spectrum antibiotic commonly used to treat bacterial infections but is associated with adverse cardiac effects, including oxidative damage and myocardial inflammation. This study aims to explore the histopathological and biochemical changes, including serum interleukin-10 levels, induced by azithromycin in the hearts of male albino rats and to evaluate the protective role of combined selenium and vitamin E treatment. Forty rats were divided into four groups: a control group, an azithromycin treatment group, selenium and vitamin E treatment group, and a combined treatment group receiving both azithromycin, selenium, and vitamin E. Results showed that the azithromycin-treated group exhibited significant increases in interleukin-10 levels, myocardial fibrosis, and cell structure degeneration, while combined selenium and vitamin E treatment markedly reduced these adverse effects, indicating a protective effect. This study concludes that selenium and vitamin E provide a protective effect against azithromycin-induced cardiac toxicity, suggesting that concurrent antioxidant therapy may help safeguard the heart during azithromycin treatment.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101860"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity evaluation of microbial sophorolipids and glucolipids using normal human dermal fibroblasts (NHDF) in vitro","authors":"Sergio Oliveira Formoso ,&nbsp;Vincent Chaleix ,&nbsp;Niki Baccile ,&nbsp;Christophe Helary","doi":"10.1016/j.toxrep.2024.101862","DOIUrl":"10.1016/j.toxrep.2024.101862","url":null,"abstract":"<div><div>Fibroblasts are considered a key player in the wound healing process. Although this cellular family is constituted by several distinct subtypes, dermal fibroblasts are crucial thanks to their ability to secrete pro-regenerative growth factors, extracellular matrix (ECM) proteins and their immune and anti-inflammatory role. Sophorolipids (SL), sophorosides (SS) and glucolipids (G), mono-unsaturated (C18:1) or saturated (C18:0), glycolipids derived from microbial fermentation of wild type or engineered yeast <em>Starmerella bombicola</em>, constitute a novel sustainable class of bio-based chemicals with interesting physicochemical characteristics, which allow them to form soft diverse structures from hydrogels to vesicles, micelles or complex coacervates with potential interest in skin regeneration applications. In this study, we first tested the cytocompatibility of a broad set of molecules from this family on normal human dermal fibroblasts (NHDF). Our results show that, up to an upper threshold (0.1 % w/v), the microbial glycolipids (SL-C18:1, G-C18:1, SS_bola-C18:1, SL-C18:0 and G-C18:0) under study were able to sustain cell growth. Furthermore, we selected the least cytotoxic glycolipids (SL-C18:1, SS_bola-C18:1, SL-C18:0) to study their potential to promote wound healing by measuring the gene expression of several key skin regeneration markers (i.e. collagen, elastin, transforming growth factor β, fibroblast growth factor …) using qPCR. Unfortunately, none of these glycolipids modulated the gene expression of molecules involved in tissue repair. However, this study aims to encourage the community to test this novel class of molecules for novel high-end biomedical applications.</div></div><div><h3>Importance</h3><div>Biosurfactants prepared by microbial fermentation are natural amphiphiles of growing importance, with the goal of replacing synthetic surfactants in commercial formulations. However, their cytotoxicity profile is still poorly known, especially for new molecules like single-glucose lipids or bolaform sophorolipids. This wants to contribute to all those applications, which could be developed with biosurfactants in contact with the skin (cosmetics, wound healing). We test the cytotoxicity of five structurally-related molecules (C18:1 and C18:0 sophorolipids, C18:1 and C18:0 single-glucose lipids, C18:1 di-sophoroside) against normal human dermal fibroblasts (NHDF) and evaluate the metabolic activity of the least toxic among them. To the best of our knowledge, cytotoxicity of these molecules, and of microbial biosurfactants in general, was never tested against NHDF.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101862"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microplastics bioaccumulation in fish: Its potential toxic effects on hematology, immune response, neurotoxicity, oxidative stress, growth, and reproductive dysfunction","authors":"Tapas Ghosh","doi":"10.1016/j.toxrep.2024.101854","DOIUrl":"10.1016/j.toxrep.2024.101854","url":null,"abstract":"<div><div>After being exposed, microplastics mostly bioaccumulated in guts and gills of fish, then, through circulation, spread and bioaccumulated in other tissues. Circulatory system of fish is impacted by the microplastic bioaccumulation in their tissues, influencing a number of hematological indices that are connected with immunity, osmotic pressure, blood clotting, molecular transport and fat metabolism. Variables like size, dose, duration, food consumption and species, all affect the bioaccumulation and toxicity of the microplastic, rather than the exposure routes. Microplastics lead to an imbalance in the generation of ROS and antioxidant defense of fish, which resulting in oxidative injury. Moreover, microplastics affect immunological responses through physico-chemical damage, hence produce neurotoxicity and modifies the activity of the acetylcholine esterase. Exposure to microplastics caused damage to the hepatic and gut tissue, affect intestinal barrier function and dysbiosis of microbial composition, altered the metabolism of host, affecting the activities of the digestive enzymes, eventually affecting the growth performance of fish. Microplastics exposure target the HPG axis and interfere with the process of steroidogenesis, apoptosis of the gonadal tissue, ultimately causing reproductive dysfunction. Fish exposed to microplastics have a range of toxic effects <em>viz.</em> alteration to immune, antioxidant and hematological indices, bioaccumulation, neurotoxicity, growth and reproductive dysfunction, all were examined in this present review by using different indicators.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101854"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural hemozoin and β-hematin induce tissue damage and apoptosis in human placental explants","authors":"Carolina López-Guzmán ,&nbsp;Julieth Herrera ,&nbsp;Julián Zapata ,&nbsp;Adriana Pabón ,&nbsp;Urlike Kemmerling Weis ,&nbsp;Ana María Vásquez","doi":"10.1016/j.toxrep.2024.101857","DOIUrl":"10.1016/j.toxrep.2024.101857","url":null,"abstract":"<div><div>Hemozoin (HZ) is a waste product of hemoglobin digestion by <em>Plasmodium</em> and has been implicated in several pathological processes, including inflammation, oxidative stress, endothelial dysfunction, and immune dysregulation. Studying the effects of HZ on the human placenta is essential to understanding the impact of malaria infection during pregnancy. The present study explored the impact of HZ produced by <em>Plasmodium</em> and β-hematin, referred to here as natural HZ (nHZ) and synthetic HZ (sHZ), respectively, on human placental explants exposed <em>in vitro</em>.</div></div><div><h3>Methodology</h3><div>nHZ was derived from <em>Plasmodium falciparum</em> cultures and isolated using magnetic MACS® Separation Columns (Miltenyi Biotec, Auburn, CA) <span><span>[1]</span></span>. sHZ was synthesized from hemin closure in an aqueous solution. Both nHZ and sHZ were characterized by infrared spectroscopy and scanning electron microscopy. Human placental explants (HPE) were exposed to 5 and 10 μg/mL of nHZ and sHZ for 24 h, and tissue integrity was studied using histological and immunohistochemical techniques.</div></div><div><h3>Results</h3><div>The studies have demonstrated that the exposition of both the nHZ and sHZ to placental tissue are comparable and cause effects in increased STB detachment, dysregulation of collagen distribution in the villous stroma, and increase in the frequency of cell apoptosis. This contributes to the understanding of the pathophysiology of malaria in pregnancy using synthetic products such as β-hematin.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101857"},"PeriodicalIF":0.0,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}