Toxicology Mechanisms and Methods最新文献

{"title":"The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using <i>in silico</i> toxicity prediction platform ProTox- 3.0.","authors":"Priyanka Banerjee, Onur Ulker, Irem Ozkan, Ozge Cemiloglu Ulker","doi":"10.1080/15376516.2024.2382815","DOIUrl":"https://doi.org/10.1080/15376516.2024.2382815","url":null,"abstract":"<p><p>From the past to the present, many chemicals have been used for the purpose of flame retardant. Due to PBDEs' (Polybrominated diphenyl ether) lipophilic and accumulative properties, some of them are banned from the market. As an alternative to these chemicals, OPFRs (organophosphorus flame retardants) have started to be used as flame retardants. In this article, acute toxicity profiles, mutagenicity, carcinogenicity, blood-brain barrier permeability, ecotoxicity and nutritional toxicity as also AHR, ER affinity and MMP, aromatase affinity, CYP2C9, CYP3A4 interaction of the of 16 different compounds of the OPFRs were investigated using a computational toxicology method; ProTox- 3.0. According to our results, eight compounds were found to be active in terms of carcinogenic effect, whereas two compounds were found to be active for mutagenicity. On the other hand, all compounds were found to be active in terms of blood-barrier permeability. Fourteen compounds and four compounds are found to have ecotoxic and nutritional toxic potency, respectively. Eight compounds were determined as active to AhR, and four chemicals were found to be active in Estrogen Receptor alpha. Eight chemicals were found to be active in terms of mitochondrial membrane potency. Lastly, three chemicals were found to be active in aromatase enzymes. In terms of CYP interaction potencies, eight compounds were found to be active in both CYP2C9 and CYP3A4. This research provided novel insights into the potential toxic effects of OPFRs. However, further studies are needed to evaluate their toxicity. Moreover, these findings lay the groundwork for <i>in vitro</i> and <i>in vivo</i> toxicity research.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-11"},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic exploration of 6-shogaol's preventive effects on azoxymethane and dextran sulfate sodium -induced colorectal cancer: involvement of cell proliferation, apoptosis, carcinoembryonic antigen, wingless-related integration site signaling, and oxido-inflammation.","authors":"Ebenezer Olatunde Farombi, Babajide Oluwaseun Ajayi, Olufunke Florence Ajeigbe, Opeyemi Rabiat Maruf, Daniel Abu Anyebe, Ifeoluwa Tobi Opafunso, Isaac Adegboyega Adedara","doi":"10.1080/15376516.2024.2381798","DOIUrl":"https://doi.org/10.1080/15376516.2024.2381798","url":null,"abstract":"<p><p>Colorectal cancer (CRC) poses a significant global health burden, being the third most prevalent cancer and the second most significant contributor to cancer-related deaths worldwide. Preventive strategies are crucial to combat this rising incidence. 6-shogaol, derived from ginger, has shown promise in preventing and treating various cancers. This study investigated the preventive effects of 6-shogaol on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC in mice. Forty male BALB/c mice were randomly divided into control, 6-shogaol, AOM + DSS, and 6-shogaol + AOM + DSS. Mice in the control group received corn oil for 16 weeks, while those in the 6-Shogaol group were administered 20 mg/kg of 6-shogaol for 16 weeks. The AOM + DSS group received a single intraperitoneal dose (<i>ip</i>) of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The 6-shogaol + AOM + DSS group received both 6-shogaol for 16 weeks and a single <i>ip</i> of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The AOM + DSS-treated mice exhibited reduced food consumption, colon weight, and colon length, along with increased tumor formation. Co-administration of 6-shogaol effectively reversed these changes, inhibiting CRC development. Histopathological analysis revealed protective effects of 6-shogaol against colonic insults and modulation of inflammatory responses. 6-shogaol significantly reduced Carcinoembryonic antigen and Kiel 67 levels, indicating inhibition of tumor cell proliferation. Mechanistically, 6-shogaol promoted apoptosis by upregulating protein 53 and caspase-3 expression, and it effectively restored the balance of the Wingless-related integration site signaling pathway by regulating β-catenin and adenomatous polyposis coli levels. Moreover, 6-shogaol demonstrated anti-inflammatory effects, reducing myeloperoxidase, Tumor necrosis factor alpha, and cyclooxygenase-2 levels in AOM/DSS-treated mice. Additionally, 6-shogaol restored redox homeostasis by reducing lipid peroxidation and nitrosative stress and enhancing antioxidant enzyme activities. The findings suggest that 6-shogaol inhibits cell proliferation, induces apoptosis, regulates Wnt signaling, suppresses inflammation, and restores redox homeostasis, providing comprehensive insights into its potential therapeutic benefits for CRC.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leflunomide-induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κb signaling interplay.","authors":"Abeer A Rahman, Ann Hegazy, Lamiaa M Elabbasy, Mohamed Z Shoaeir, Tarek M Abdel-Aziz, Awad S Abbas, Heba W Z Khella, Amira H Eltrawy, Reem Alshaman, Sheka Yagub Aloyouni, Afaf A Aldahish, Sawsan A Zaitone","doi":"10.1080/15376516.2024.2322666","DOIUrl":"10.1080/15376516.2024.2322666","url":null,"abstract":"<p><p>Leflunomide (LFND) is an immunosuppressive and immunomodulatory disease-modifying antirheumatic drug (DMARD) that was approved for treating rheumatoid arthritis. LFND-induced cardiotoxicity was not fully investigated since its approval. We investigated the cardiac injury in male mice and identified the role of nuclear factor erythroid 2-related factor 2/nuclear factor-κ B (Nrf2/NF-κB) signaling. Male albino mice were assigned into five groups as control, vehicle, and LFND (2.5, 5, and 10 mg/kg). We investigated cardiac enzymes, histopathology, and the mRNA expression of Nrf2, NF-κB, BAX, and tumor necrosis factor-α (TNF-α). The bioinformatic study identified the interaction between LFND and Nrf2/NF-κB signaling; this was confirmed by amelioration in mRNA expression (0.5- to 0.34-fold decrease in Nrf2 and 2.6- to 4.61-fold increases in NF-κB genes) and increased (1.76- and 2.625-fold) serum creatine kinase (CK) and 1.38- and 2.33-fold increases in creatine kinase-MB (CK-MB). Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear, and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration and highlights, for the first time, dysregulation in Nrf2/NF-κB signaling.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"639-653"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renoprotective effect of hyperin against CdCl₂ prompted renal damage by activation of Nrf-2/Keap-1 ARE pathway in male mice.","authors":"Iserhienrhien O Lucky, Iyoha I Aisuhuehien, Memudu E Adejoke","doi":"10.1080/15376516.2024.2329655","DOIUrl":"10.1080/15376516.2024.2329655","url":null,"abstract":"<p><strong>Objectives: </strong>This study explored the mitigating properties of hyperin (HYP) on renotoxicity induced by cadmium chloride (CdCl₂).</p><p><strong>Methods: </strong>Four groups of seven male albino mice each were used in this experiment. Group 1 served as the control, receiving no treatment. Group 2 received daily oral gavage of CdCl₂ at 0.3 mg/kg body weight for 28 d. Group 3 received both CdCl₂ (0.3 mg/kg) and HYP (100 mg/kg) daily using the same administration method. Finally, Group 4 received only HYP (100 mg/kg) daily.</p><p><strong>Results: </strong>Cd exposure significantly increased kidney dysfunction markers (blood urea nitrogen and creatinine) and oxidative stress (reactive oxygen species [ROS] and malondialdehyde [MDA]). Conversely, it decreased antioxidant enzyme activities (glutathione peroxidase (GPx] and catalase [CAT]) and glutathione (GSH) levels. Nuclear factor erythroid 2-related factor 2 (Nrf-2) and antioxidant gene expression decreased, while Kelch-like ECH-associated protein 1 expression increased. Additionally, Cd exposure increased inflammatory mediators (nuclear factor kappa B, tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and cyclooxygenase-2) and apoptotic markers (Bax and caspase-3), alongside decreased Bcl-2 expression and renal tissue abnormalities. Mitochondrial dysfunction manifested with diminished activities of Krebs cycle and respiratory chain enzymes, and reduced mitochondrial membrane potential. Co-treatment with HYP significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties.</p><p><strong>Conclusion: </strong>HYP co-treatment significantly attenuated CdCl₂-induced renal damage in mice, suggesting its potential as a protective agent against Cd-induced kidney toxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"717-726"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometric methods for evaluation of voriconazole avian pharmacokinetics and the inhibition of its cytochrome P450-induced metabolism.","authors":"Andreas F Lehner, Sharmie D Johnson, Levent Dirikolu, Margaret Johnson, John P Buchweitz","doi":"10.1080/15376516.2024.2322675","DOIUrl":"10.1080/15376516.2024.2322675","url":null,"abstract":"<p><p>Invasive fungal aspergillosis is a leading cause of morbidity and mortality in many species including avian species such as common ravens (<i>Corvus corax</i>). Methods were developed for mass spectral determination of voriconazole in raven plasma as a means of determining pharmacokinetics of this antifungal agent. Without further development, GC/MS/MS (gas chromatography-tandem quadrupole mass spectrometry) proved to be inferior to LC/MS/MS (liquid chromatography-tandem quadrupole mass spectrometry) for measurement of voriconazole levels in treated raven plasma owing to numerous heat-induced breakdown products despite protection of voriconazole functional groups with trimethylsilyl moieties. LC/MS/MS measurement revealed in multi-dosing experiments that the ravens were capable of rapid or ultrarapid metabolism of voriconazole. This accounted for the animals' inability to raise the drug into the therapeutic range regardless of dosing regimen unless cytochrome P450 (CYP) inhibitors were included. Strategic selection of CYP inhibitors showed that of four selected compounds including cimetidine, enrofloxacin and omeprazole, only ciprofloxacin (Cipro) was able to maintain voriconazole levels in the therapeutic range until the end of the dosing period. The optimal method of administration involved maintenance doses of voriconazole at 6 mg/kg and ciprofloxacin at 20 mg/kg. Higher doses of voriconazole such as 18 mg/kg were also tenable without apparent induction of toxicity. Although most species employ CYP2C19 to metabolize voriconazole, it was necessary to speculate that voriconazole might be subject to metabolism by CYP1A2 in the ravens to explain the utility of ciprofloxacin, a previously unknown enzymatic route. Finally, despite its widespread catalog of CYP inhibitions including CYP1A2 and CYP2C19, cimetidine may be inadequate at enhancing voriconazole levels owing to its known effects on raising gastric pH, a result that may limit voriconazole solubility.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"654-668"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating oxidative stress, apoptosis, and mitochondrial dysfunctions on cardiotoxicity induced by aluminum phosphide pesticide using resveratrol.","authors":"Deema K Sabir, Abeer Al-Masri, Munirah F Aldayel, Abeer A Sharaf","doi":"10.1080/15376516.2024.2331768","DOIUrl":"10.1080/15376516.2024.2331768","url":null,"abstract":"<p><p>The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 μM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, <i>via</i> its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"727-735"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing the impact of synthetic and natural steroids: a study of cytochrome P450 metabolism, morphological alterations through metabolomics, and histopathological Examination.","authors":"Esat Mahmut Kocaman, Onur Şenol, Serkan Yıldırım, Muhammed Atamanalp, Sinan Özcan, İsmail Bolat, Arzu Ucar, Metin Kiliçlioğlu, Veysel Parlak, Mehmet Takkac, Gonca Alak","doi":"10.1080/15376516.2024.2322006","DOIUrl":"10.1080/15376516.2024.2322006","url":null,"abstract":"<p><p>This study focuses on the comparative metabolic profiling and effects of two steroid types: natural and synthetic, specifically 17α-methyl testosterone (17α-MT) at varying concentrations (1.5, 2, and 3 mg/kg) in rainbow trout (<i>Oncorhynchus mykiss</i>). Over a 75-day feeding trial, growth metrics, such as feed efficiency, daily specific growth, live weight gain, total weight gain, and survival rate were systematically monitored every 15 days. At the end of the feeding trial, histopathology, immunohistochemistry, and metabolome analyses were performed in the high-concentration groups (3 mg/kg natural and 3 mg/kg synthetic), in which the lowest survival rate was determined. Key findings reveal that the type of hormone significantly influences growth parameters. While some natural steroids enhanced certain growth aspects, synthetic variants often yielded better results. The metabolomic analysis highlighted significant shifts in the metabolism of tryptophan, purine, folate, primary bile acids, phosphonates, phosphinates, and xenobiotics <i>via</i> cytochrome P450 pathways. Histopathologically, the natural hormone groups showed similar testicular, hepatic, muscular, gill, cerebral, renal, and intestinal tissue structures to the control, with minor DNA damage and apoptosis observed through immunohistochemistry. Conversely, the synthetic hormone groups exhibited moderate DNA damage and mild degenerative and necrotic changes in histopathology.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"628-638"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4.","authors":"Bhagawati Saxena, Pragnesh Parmar, Heena Chauhan, Pooja Singh, Ashok Kumar Datusalia, Vivek Kumar Vyas, Nagja Tripathi, Jigna Shah","doi":"10.1080/15376516.2024.2329653","DOIUrl":"10.1080/15376516.2024.2329653","url":null,"abstract":"<p><p>Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl₃) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl₃-induced neurotoxicity <i>in vitro</i> and <i>in vivo</i> studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl₃ (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (<i>h</i>MD-2) was investigated. AlCl₃ (25 mg/kg/d, <i>i.p.</i>) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, <i>i.p.</i>) was given along with AlCl₃. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with <i>h</i>MD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl₃ in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl₃-induced altered cell morphology. AlCl₃ administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl₃-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl₃ administration in rats. Thus, taxifolin may protect the brain against AD.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"703-716"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A trend over time study of hepatic Farnesoid-X-activated receptor and its downstream targets modulation by valproic acid in mice","authors":"Amir Saamaan Fattahi, Azadeh Khalili, Seyed Ali Hashemi, Parvaneh Najafizadeh, Roham Mazloom, Sara Khodayar, Gholamreza Bayat","doi":"10.1080/15376516.2024.2364192","DOIUrl":"https://doi.org/10.1080/15376516.2024.2364192","url":null,"abstract":"Valproic acid (VA) is a broad-spectrum anticonvulsant agent that acts through several molecular mechanisms to control different types of seizures. The main concern of the drug is its liver toxicity...","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":"16 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141551004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering molecular basis of pesticide-induced recurrent pregnancy loss: insights from transcriptomics analysis.","authors":"Muhammad Luthfi, R B Pandey, Yong-Chao Su, Pornthep Sompornpisut","doi":"10.1080/15376516.2024.2307975","DOIUrl":"10.1080/15376516.2024.2307975","url":null,"abstract":"<p><p>Recent studies have revealed a notable connection between pesticide exposure and Recurrent Pregnancy Loss (RPL), yet the precise molecular underpinning of this toxicity remains elusive. Through the alignment of Differentially Expressed Genes (DEGs) of healthy and RPL patients with the target genes of 9 pesticide components, we identified a set of 12 genes responsible for RPL etiology. Interestingly, biological process showed that besides RPL, those 12 genes also associated with preeclampsia and cardiovascular disease. Enrichment analysis showed the engagement of these genes associated with essential roles in the molecular transport of small molecules, as well as the aldosterone-regulated sodium reabsorption, endocrine and other factor-regulated calcium reabsorption, mineral absorption, ion homeostasis, and ion transport by P-type ATPases. Notably, the crosstalk targets between pesticide components played crucial roles in influencing RPL results, suggesting a role in attenuating pesticide agents that contribute to RPL. It is important to note that non-significant concentration of the pesticide components observed in both control and RPL samples should not prematurely undermine the potential for pesticides to induce RPL in humans. This study emphasizes the complexity of pesticide induced RPL and highlights avenues for further research and precautionary measures.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"527-544"},"PeriodicalIF":3.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}