Toxicology Reports最新文献

{"title":"Podocyte-related biomarkers' role in evaluating renal toxic effects of silver nanoparticles with the possible ameliorative role of resveratrol in adult male albino rats","authors":"Eman El-Sayed Khayal ,&nbsp;Mona G. Elhadidy ,&nbsp;Sulaiman Mohammed Alnasser ,&nbsp;Manal Mohammad Morsy ,&nbsp;Azza I. Farag ,&nbsp;Samah A. El-Nagdy","doi":"10.1016/j.toxrep.2024.101882","DOIUrl":"10.1016/j.toxrep.2024.101882","url":null,"abstract":"<div><div>Extensive uses of silver nanoparticles (Ag NPs) in different industries result in exposure to these nanoparticle imperatives in our daily lives. Resveratrol is found in many plants as a natural compound. The present study aimed to estimate the renal toxic effects of Ag NPs in adult male albino rats and the underlying relevant mechanisms while studying the possible role of resveratrol in ameliorating these effects. Thirty adult albino rats were split into 5 groups; control, vehicle, resveratrol (30 mg/kg), Ag NPs (300 mg/kg), and resveratrol + Ag NPs groups. The treatments were given orally for 4 weeks. Ag NPs group displayed a reduction in kidney weight ( absolute and relative), excess in urinary levels of kidney injury molecule, neutrophil gelatinase-associated lipocalin, cystatin, and blood kidney biomarkers (creatinine, urea, and potassium), increases in oxidative stress markers with the reduction in antioxidant markers, and decreases in serum sirtuin 1(SIRT1) level. Upregulation of interleukin 1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 gene expressions with downregulation of nephrin and podocin gene expressions in renal tissues were also observed. These changes were associated with histological alterations of the glomeruli and tubules, and increased area percentage of collagen fiber. A significant increase in the optical density of <em>transforming growth factor-beta</em> 1 and claudin-1 immunostaining was detected in the Ag NPs group when compared to other groups. All these changes were alleviated by the usage of resveratrol through its anti-oxidant, anti-inflammatory, and activation of SIRT1 recommending its use as a renoprotective agent.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101882"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029466","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":"Endocrine-disrupting chemicals (EDCs) and epigenetic regulation in embryonic development: Mechanisms, impacts, and emerging trends","authors":"Clinton Ayodeji Akanbi ,&nbsp;Damilare Emmanuel Rotimi ,&nbsp;Adebola Busola Ojo ,&nbsp;Oluwafemi Adeleke Ojo","doi":"10.1016/j.toxrep.2024.101885","DOIUrl":"10.1016/j.toxrep.2024.101885","url":null,"abstract":"<div><div>Endocrine-disrupting chemicals (EDCs) are prevalent ecological pollutants that interfere with hormonal systems and pose serious health risks to the public, especially during critical developmental windows. Well-known EDCs, such as bisphenol A (BPA) and phthalates, can alter gene regulation and induce epigenetic modifications that worsen reproductive and developmental disorders. This review explores the intricate relationships that exist among epigenetic mechanisms, EDCs, and embryonic development, with a focus on significant modifications such as DNA methylation, histone modifications, and noncoding RNA dynamics that are critical for cellular differentiation. We review the possible health implications of EDC-induced epigenetic changes, focusing on how they could increase susceptibility to diseases. In addition, we provide a critical review of the available treatments aimed at reversing these epigenetic changes and highlight the groundbreaking technologies of high-throughput sequencing and CRISPR-based epigenome editing that are redefining the understanding of EDC effects. This thorough analysis highlights the necessity of efficient regulations that lower EDC exposure as well as the possibility of customized preventative measures to ensure developmental safety.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101885"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103710","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":"Genotoxicity study of Cannabis sativa L. extract","authors":"Alana Costa ,&nbsp;Arquimedes Gasparotto Jr. ,&nbsp;Cícero Pereira ,&nbsp;Emerson Lourenço ,&nbsp;Alana Garcia ,&nbsp;Helena Joaquim","doi":"10.1016/j.toxrep.2024.101864","DOIUrl":"10.1016/j.toxrep.2024.101864","url":null,"abstract":"<div><div><em>Cannabis sativa</em> L., a member of the Cannabaceae family, has been thoroughly investigated for its diverse therapeutic properties, primarily attributed to cannabinoids such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Secondary, metabolites like terpenes also exhibit pharmacological effects. This study examined the genotoxicity of a whole Cannabis sativa flower extract 160.32 mg/mL using three OECD-recommended protocols: the Ames test, micronucleus test, and comet assay. Five groups of six Wistar rats were used. Three doses of the extract (500, 1000, and 2000 mg/kgbw) or negative control (placebo) were administered orally, while cyclophosphamide monohydrate (20 mg/kgbw) was used as a positive control via intraperitoneal injection. Blood was collected for the comet test, and the animals were euthanized for bone marrow collection for the micronucleus test. The Cannabis extract did not increase the number of revertant bacterial colonies at (375, 250, 125, and 62.5 μg/plate) in TA100 or TA98, nor did it affect the number of micronucleated polychromatic erythrocytes (MNPCEs) or the ratio of polychromatic to normochromatic erythrocytes (PCEs/NCEs). It also did not alter the index or frequency of DNA damage in hematopoietic cells. These results suggest no genotoxic effects, supporting its potential therapeutic use.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101864"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012239","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":"Metabolomics integrated genomics approach: Understanding multidrug resistance phenotype in MCF-7 breast cancer cells exposed to doxorubicin and ABCA1/EGFR/PI3k/PTEN crosstalk","authors":"Mai O. Kadry ,&nbsp;Gamal Eldein Fathy Abd-Ellatef ,&nbsp;Naglaa M. Ammar ,&nbsp;Heba A. Hassan ,&nbsp;Noha S. Hussein ,&nbsp;Nahla N. Kamel ,&nbsp;Maha M. Soltan ,&nbsp;Rehab M. Abdel-Megeed ,&nbsp;Abdel-Hamid Z. Abdel-Hamid","doi":"10.1016/j.toxrep.2024.101884","DOIUrl":"10.1016/j.toxrep.2024.101884","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Resistance of cancer cells, especially breast cancer, to therapeutic medicines represents a major clinical obstacle that impedes the stages of treatment. Carcinoma cells that acquire resistance to therapeutic drugs can reprogram their own metabolic processes as a way to overcome the effectiveness of treatment and continue their reproduction processes. Despite the recent developments in medical research in the field of drug resistance, which showed some explanations for this phenomenon, the real explanation, along with the ability to precisely predict the possibility of its occurrence in breast cancer cells, still necessitates a deep consideration of the dynamics of the tumor's response to treatment. For this purpose the current study, combined both &lt;em&gt;in vitro&lt;/em&gt; metabolomics and &lt;em&gt;in vivo&lt;/em&gt; genomics analysis as the most advanced omics technologies that can provide a potential en route for inventing novel strategies to perform prospective, prognostic and diagnostic biomarkers for drug resistance phenomena in mammary cancer. Doxorubicin is the currently available breast cancer chemotherapeutic medication nevertheless; it was demonstrated to cause drug resistance, which impairs patient survival and prognosis by prompting proliferation, cell cycle progression, and preventing apoptosis, interactions between signaling pathways triggered drug resistance. In this research, &lt;em&gt;in vitro&lt;/em&gt; metabolomics analysis based on GC-MS coupled with multivariable analysis was performed on MCF-7 and DOX resistant cell lines; MCF-7/adr cultured cells in addition to, further &lt;em&gt;in vivo&lt;/em&gt; confirmation via inducing mammary cancer in rats via two doses of 7,12-dimethylbenz(a) anthracene (DMBA) (50 mg/kg and 25 mg/kg) proceeded by doxorubicin (5 mg/kg) treatment for one month. The metabolomics &lt;em&gt;in vitro&lt;/em&gt; results pointed out that mannitol, myoinositol, glycine, α-linolenic acid, oleic acid and stearic acid have AUC values: 0.14, 0.5, 0.7, 0.1, 0.02, −0.02 (1, 1) respectively. Glycine and myoinositol metabolites provided the best discriminative power in the wild and resistance MCF-7 phenotypes. Meanwhile, &lt;em&gt;in vivo&lt;/em&gt; results revealed a significant crosstalk between the alternation in oxidative stress biomarkers as well as Arginase II tumor biomarker and the molecular assessment of ABCA1 and P53 gene expression that displayed a marked reduction in addition to, the obvious elevation in resistance and apoptotic biomarkers EGFR/PI3k/AKT/PTEN signaling pathway upon DMBA administration. Data revealed a significant alternation in signaling pathways related to resistance upon doxorubicin administration that affect lipid metabolism in breast cancer. In conclusion, Metabolomics integrated genomics analysis may be promising in understanding multidrug resistance phenotype in MCF-7 breast cancer cells exposed to doxorubicin through modulating ABCA1/EGFR/P53/PI3k/PTEN signaling pathway thus metabolic biomarkers in addition to molecular biomarkers eluci","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101884"},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068223","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":"Exploring the biological impact of bacteria-derived indole compounds on human cell health: Cytotoxicity and cell proliferation across six cell lines","authors":"Alisha Janiga-MacNelly ,&nbsp;Maddison Vrazel ,&nbsp;Ava E. Roat ,&nbsp;Maria Teresa Fernandez-Luna ,&nbsp;Ramon Lavado","doi":"10.1016/j.toxrep.2024.101883","DOIUrl":"10.1016/j.toxrep.2024.101883","url":null,"abstract":"<div><div>Over the past two decades, research has increasingly focused on the interactions between diet, gut microbiota, and host organisms. Recent evidence suggests that tryptophan, an essential amino acid, can be metabolized by gut microbiota into indoles, which have significant biological effects. However, most research is limited to indole and its liver metabolite, indoxyl sulfate. This study examines the cytotoxic effects of five indole derivatives — indole-3-carboxylic acid (I3CA), indole-3-aldehyde (I3A), indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), and 3-methylindole (skatole, 3-MI) — on six human cell lines: adipose-derived mesenchymal stem cells (MSC), hepatocellular carcinoma (HepG2), liver progenitor cells (HepaRG), colorectal carcinoma cells (Caco-2), breast cancer cells (T47D), and lung fibroblast (MRC-5). Results show no sensitivity to indole itself across cell lines. MRC-5 was sensitive to all other compounds (EC50 0.52–49.8 µM). MSCs responded to IPA, I3CA, I3A, and 3-MI (EC50 0.33–1.87 µM), while HepaRG cells were affected by IAA, I3CA, I3A, and 3-MI (EC50 1.98–66.4 µM). T47D cells were sensitive to IPA and IAA, and Caco-2 cells only to IAA (EC50 2.02, 1.68, 0.52 µM, respectively). HepG2 cells showed no change in viability. AhR activation in HepG2-AhR-Lucia cells was triggered by all derivatives, particularly I3A, IPA, and I3CA. Growth experiments revealed I3CA decreased Caco-2 proliferation while increasing T47D proliferation. The findings suggest indole derivatives are generally non-cytotoxic to carcinomas but may adversely affect stem cells, with effects varying across cell lines.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101883"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024716","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":"Corrigendum regarding missing or incorrect declaration of competing interest statements in previously published articles","authors":"","doi":"10.1016/j.toxrep.2024.101881","DOIUrl":"10.1016/j.toxrep.2024.101881","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101881"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984663","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":"Harnessing machine learning in contemporary tobacco research","authors":"Krishnendu Sinha ,&nbsp;Nabanita Ghosh ,&nbsp;Parames C. Sil","doi":"10.1016/j.toxrep.2024.101877","DOIUrl":"10.1016/j.toxrep.2024.101877","url":null,"abstract":"<div><div>Machine learning (ML) has the potential to transform tobacco research and address the urgent public health crisis posed by tobacco use. Despite the well-documented health risks, cessation rates remain low. ML techniques offer innovative solutions by analyzing vast datasets to uncover patterns in smoking behavior, genetic predispositions, and effective cessation strategies. ML can predict smoking-induced non-communicable diseases (SiNCDs) like lung cancer and postmenopausal osteoporosis by identifying biomarkers and genetic profiles, generating personalized predictions, and guiding interventions. It also improves prediction of infant tobacco smoke exposure, distinguishes secondhand and thirdhand smoke, and enhances protection strategies for children. Data-driven, personalized approaches using ML track real-time data for personalized feedback and offer timely interventions, continuously improving cessation strategies. Overall, ML provides sophisticated predictive models, enhances understanding of complex biological mechanisms, and enables personalized interventions, demonstrating significant potential in the fight against the tobacco epidemic.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101877"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024734","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":"Methionine mitigates aflatoxicosis in quail chicks by improving gut microbiota, immunity, and meat quality","authors":"Adel Ghorbani,&nbsp;Mahmoud Ghazaghi,&nbsp;Farzad Bagherzadeh-Kasmani,&nbsp;Mohammad Rokouei,&nbsp;Mehran Mehri","doi":"10.1016/j.toxrep.2024.101875","DOIUrl":"10.1016/j.toxrep.2024.101875","url":null,"abstract":"<div><div>This study aimed to investigate the effects of dietary methionine (Met) supplementation on performance, immunity, and meat quality in growing Japanese quail exposed to aflatoxin B₁ (AFB₁)-contaminated diets. Nine experimental diets were formulated, incorporating three levels of dietary Met (5.0, 6.0, and 7.0 g/kg) and three levels of AFB₁ (0.0, 2.5, and 5.0 mg/kg) in a completely randomized design and fed from d 8 post-hatch to d 35 of age. The results revealed that increasing dietary Met levels significantly improved body weight gain (BWG; P &lt; 0.001), feed conversion ratio (FCR; P &lt; 0.001), and feed intake (FI; P &lt; 0.001), while counteracting the negative effects of AFB₁ on these performance parameters. Dietary Met supplementation also exerted a protective effect against elevated hepatic enzyme levels (AST, P &lt; 0.001; ALT, P &lt; 0.001; ALP, P = 0.001; and LDH, P &lt; 0.001) and serum uric acid levels (P &lt; 0.001) induced by AFB₁. Furthermore, dietary Met enhanced humoral immunity responses by increasing antibody production against sheep red blood cell antigen (P &lt; 0.001) and hemagglutination inhibition response (P &lt; 0.001), mitigating the AFB₁-induced immune impairment. Meat quality parameters, including pH (P = 0.04), drip loss (P &lt; 0.00₁), and malondialdehyde concentration (P &lt; 0.001), were significantly influenced by the interaction between dietary Met and AFB₁. Lastly, dietary Met supplementation effectively counteracted AFB₁'s detrimental effects on ileal lactic acid bacteria populations (P &lt; 0.001). In conclusion, dietary Met supplementation shows promise as a nutritional intervention to alleviate the harmful effects of AFB₁ exposure in Japanese quail, particularly in improving food quality and overall health.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101875"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012243","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":"Intravenous indoxacarb toxicity: A rare case of unusual exposure with clinical implications","authors":"Hamidreza Farhadi Rad ,&nbsp;Maryam Shahrokhi ,&nbsp;Habibeh Mashayekhi-sardoo ,&nbsp;Amir Amirkhani ,&nbsp;Hamidreza Ghasemirad","doi":"10.1016/j.toxrep.2024.101876","DOIUrl":"10.1016/j.toxrep.2024.101876","url":null,"abstract":"<div><div>A 25-year-old male farmer presented to the emergency department with confusion, cyanosis, and low oxygen saturation (SpO₂) after an intentional intravenous injection of indoxacarb. Initial laboratory tests revealed severe methemoglobinemia (40.8 %), hypokalemia, hyponatremia, leukocytosis, and coagulation abnormalities. Despite supplemental oxygen, SpO₂ remained low, prompting Intensive Care Unit (ICU) admission. Methylene blue (2 mg/kg IV loading dose, followed by 1 mg/kg after one hour) was administered to reduce methemoglobin levels, which decreased to 2 % within six hours, leading to significant clinical improvement. By the second day, the patient’s symptoms resolved, and SpO₂ stabilized at 96 % on room air. Following stabilization, he was transferred to the toxicology ward in good condition. This case highlights clinical presentation, management, and rapid recovery in an instance of intravenous indoxacarb poisoning.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101876"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143103747","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":"Inhalation exposure to dihydroxyacetone promotes lung injury and pulmonary fibrosis in A/J mice","authors":"Arlet Hernandez ,&nbsp;Hailey Levi ,&nbsp;Juan Xavier Masjoan Juncos ,&nbsp;Lilly Underwood ,&nbsp;Jenna Hedlich-Dwyer ,&nbsp;Saurabh Aggarwal ,&nbsp;Natalie R. Gassman","doi":"10.1016/j.toxrep.2024.101878","DOIUrl":"10.1016/j.toxrep.2024.101878","url":null,"abstract":"<div><div>Acute and sub-acute exposure to dihydroxyacetone (DHA), a compound found in e-cigarette aerosols and spray tanning products, was assessed for its impact on lung injury in A/J mice. Mice were exposed to inhaled DHA doses of 5, 130, and 600 µg and evaluated at 1 and 24 h post-exposure. Acute exposure to DHA led to significant inflammatory responses, indicated by increased bronchoalveolar lavage fluid (BALF) protein levels at 5, 130, and 600 µg and notably elevated inflammatory cytokines IL-6 and TNF-α 1 h post-exposure. 24 h post-exposure, the 130 and 600 µg doses showed elevated BALF cell counts. Histological analysis revealed significant alveolar damage and increased lung injury scores for the 130 and 600 µg doses. For sub-acute exposure, male and female mice were exposed to 5 µg DHA for 14 days. Increased BALF cell counts and protein levels were observed, with sex-specific differences in cytokine responses. Male mice exhibited reduced levels of IFN-γ and TNF-α, while female mice showed significant lung damage characterized by decreased alveolar density and increased collagen deposition indicative of fibrosis. Functional assessments showed mixed obstructive and restrictive lung changes. This study highlights DHA’s potential to induce acute inflammatory responses and chronic lung damage, including both emphysematous and fibrotic changes. These findings suggest that DHA exposure, particularly from aerosolized e-liquids, could contribute to respiratory complications, underscoring the need for further research on long-term exposure effects.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101878"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104187","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}