Current Research in Toxicology最新文献

{"title":"The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals","authors":"Sudarat Hadpech,&nbsp;Paleerath Peerapen,&nbsp;Visith Thongboonkerd","doi":"10.1016/j.crtox.2023.100145","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100145","url":null,"abstract":"<div><p>Calcium oxalate monohydrate (COM), the most important crystal causing kidney stone disease, upregulates lamin A/C but downregulates zonula occludens-1 (ZO-1) in renal tubular cells. While roles for F-actin and α-tubulin and their association with ZO-1 are known to regulate COM-mediated tight junction (TJ) disruption, roles of lamin A/C and its interplay with ZO-1 in COM kidney stone model remain unclear and are thus the objectives of this study. Lamin A/C was knocked down in MDCK cells by silencing RNA specific for <em>LMNA</em> (siLMNA). Both wild-type (WT) and siLMNA cells were treated with COM for 48-h compared with the untreated (control) cells. Western blotting and immunofluorescence staining revealed upregulated lamin A/C and downregulated ZO-1 in the COM-treated WT cells. siLMNA successfully reduced lamin A/C expression in both control and COM-treated cells. Nonetheless, siLMNA did not reverse the effect of COM on the decreases in ZO-1 and transepithelial resistance, but further reduced their levels in both control and COM-treated cells. Protein-protein interaction analysis demonstrated that two cytoskeletal proteins (actin and tubulin) served as the linkers to connect lamin A/C with ZO-1 and occludin (both of which are the TJ proteins). Altogether, these data implicate that lamin A/C and ZO-1 are indirectly associated to control TJ function, and ZO-1 expression is regulated by lamin A/C. Moreover, COM-induced upregulation of lamin A/C most likely serves as a compensatory mechanism to cope with the downregulation of ZO-1 during COM-mediated TJ disruption.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100145"},"PeriodicalIF":3.3,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X23000439/pdfft?md5=e8d399b693a850ebd5d17503600d5d14&pid=1-s2.0-S2666027X23000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138839707","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":"The pathogenesis of albuminuria in cadmium nephropathy","authors":"Soisungwan Satarug ,&nbsp;David A. Vesey ,&nbsp;Glenda C. Gobe ,&nbsp;Kenneth R. Phelps","doi":"10.1016/j.crtox.2023.100140","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100140","url":null,"abstract":"<div><h3>Background</h3><p>Urinary cadmium excretion (E_Cd) rises with renal tissue content of the metal. Whereas glomerulopathies are sometimes associated with massive albuminuria, tubular accumulation of Cd typically causes modest albuminuria. Since β₂-microglobulinuria (E_β2M) is an established marker of proximal tubular dysfunction, we hypothesized that a comparison of albuminuria (E_alb) to E_β2M in Cd-exposed subjects would provide evidence of similar mishandling of both proteins.</p></div><div><h3>Methods</h3><p>To depict excretion rates per functional nephron, E_Cd, E_alb, and E_β2M were normalized to creatinine clearance (C_cr), a surrogate for the glomerular filtration rate (GFR). Estimation of GFR itself (eGFR) was accomplished with CKD-EPI formulas (2009). Linear and logistic regression analyses were performed to relate E_alb/C_cr, E_β2M/C_cr, and eGFR to several independent variables. Simple linear regressions of eGFR, E_alb/C_cr, and E_β2M/C_cr on E_Cd/C_cr were examined before and after adjustment of dependent variables for age. All regressions were performed after log-transformation of ratios and standardization of all variables. Increments in E_alb/C_cr and E_β2M/C_cr and decrements in eGFR were quantified through four quartiles of E_Cd/C_cr.</p></div><div><h3>Results</h3><p>As age or E_Cd/C_cr rose, E_alb/C_cr and E_β2M/C_cr also rose, and eGFR fell. In linear regressions, slopes relating E_alb/C_cr and E_β2M/C_cr to E_Cd/C_cr were similar. After adjustment of dependent variables for age, coefficients of determination (R²) for all regressions rose by a multiple, and slopes approached unity. E_alb/C_cr and E_β2M/C_cr were similarly associated with each other. Mean E_alb/C_cr and E_β2M/C_cr rose and mean eGFR fell in stepwise fashion through quartiles of E_Cd/C_cr. Whereas E_β2M/C_cr did not vary with blood pressure, E_alb/C_cr rose in association with hypertension in two of the four quartiles.</p></div><div><h3>Conclusions</h3><p>Our data indicate that Cd in renal tissue affected tubular reabsorption of albumin and β₂M similarly in a large cohort of exposed subjects. The results suggest that Cd reduced receptor-mediated endocytosis and subsequent lysosomal degradation of each protein by a shared mechanism.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100140"},"PeriodicalIF":3.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X23000385/pdfft?md5=fb62735e49213e668766e81df7ba0200&pid=1-s2.0-S2666027X23000385-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570421","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":"Lestaurtinib induces DNA damage that is related to estrogen receptor activation","authors":"Masato Ooka ,&nbsp;Shu Yang ,&nbsp;Li Zhang ,&nbsp;Kota Kojima ,&nbsp;Ruili Huang ,&nbsp;Kouji Hirota ,&nbsp;Shunichi Takeda ,&nbsp;Menghang Xia","doi":"10.1016/j.crtox.2022.100102","DOIUrl":"10.1016/j.crtox.2022.100102","url":null,"abstract":"<div><p>A number of chemicals in the environment pose a threat to human health. Recent studies indicate estradiol induces DNA damage through the activation of the estrogen receptor alpha (ERα). Given that many environmental chemical compounds act like hormones once they enter the human body, it is possible that they induce DNA damage in the same way as estradiol, which is of great concern to females with the BRCA1 mutation. In this study, we developed an antibody-based high content method measuring γH2AX, a biomarker for DNA damage, to test a subset of 907 chemical compounds in MCF7 cells. The assay was optimized for a 1536 well plate format and had a satisfactory assay performance with Z-factor of 0.67. From the screening, we identified 128 compounds that induce γH2AX expression in the cells. These compounds were further examined for their γH2AX induction in the presence of an ER inhibitor, tamoxifen. After tamoxifen treatment, four compounds induced less γH2AX expression compared to those without tamoxifen treatment, suggesting these compounds induced γH2AX that is related to ERα activation. These four compounds were chosen for further studies to assess their ERα activating capability and <em>c-MYC</em> induction. Only lestaurtinib, a selective tyrosine kinase inhibitor, induced ERα activation, which was confirmed by both ERα beta-lactamase reporter gene assay and molecular docking analysis. Lestaurtinib also increased <em>c-MYC</em> expression, a target gene of ERα signaling, measured by the quantitative PCR method. This data suggests that lestaurtinib acts as a DNA damage inducer that is related to ERα activation.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100102"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5a/a1/main.PMC9816669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508174","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":"Detail study on the interaction between perfluorooctanoic acid (PFOA) with human hemoglobin (Hb)","authors":"N.L. Dilani Perera,&nbsp;Jovany Betancourt,&nbsp;Jaroslava Miksovska,&nbsp;Kevin E. O'Shea","doi":"10.1016/j.crtox.2023.100130","DOIUrl":"10.1016/j.crtox.2023.100130","url":null,"abstract":"<div><p>Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are often referred to as legacy perfluoroalkyl substances (PFAS). Human exposure to PFAS leads to severe negative health impacts including cancers, infertility, and dysfunction in the kidneys. Steady-state absorbance, fluorescence, and circular dichroism (CD) methods were used to study the interactions between PFOA and Hb. The results demonstrate the presence of multiple PFOA binding sites on the Hb protein. The detailed analysis of the ferric hemoglobin protein (met Hb) absorbance data as a function of PFOA concentration indicates the presence of at least two binding sites with equilibrium dissociation constants of 0.8 ± (0.2) × 10⁻⁶ M and 63 ± (15) × 10⁻⁵ M. A competitive binding study with 1,8-ANS showed PFOA can bind to the same binding site as 1,8-ANS on the Hb protein. The titration curve for PFOA binding to Hb in its CO bound form (CO-Hb) yields a single equilibrium dissociation constant of 139 ± (20) × 10⁻⁶ M. PFOA binding at low concentrations occurs at the high-affinity sites leading to the destabilization of the protein structure as reflected by changes in the CD spectrum. PFOA interactions with Hb also interfere with the kinetics of CO association to this protein. The rate for CO association to Hb increases at low PFOA concentrations, whereas at elevated PFOA concentrations, the ligand association is biphasic as a new kinetic process with a different rate constant was observed. Overall, this study provides a detailed explanation of PFOA-induced structural and conformational changes to the Hb protein based on the spectroscopy data.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100130"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/0f/main.PMC10563006.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194504","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":"Phytanic acid, an inconclusive phytol metabolite: A review","authors":"Muhammad Torequl Islam ,&nbsp;Md. Shimul Bhuia ,&nbsp;João Paulo Martins de Lima ,&nbsp;Francisco Paulo Araujo Maia ,&nbsp;Ana Beatriz Herminia Ducati ,&nbsp;Henrique Douglas Melo Coutinho","doi":"10.1016/j.crtox.2023.100120","DOIUrl":"10.1016/j.crtox.2023.100120","url":null,"abstract":"<div><p>Phytanic acid (PA: 3,7,11,15-tetramethylhexadecanoic acid) is an important biometabolite of the chlorophyll-derived diterpenoid phytol. Its biological sources (occurrence) and ADME (absorption, distribution, metabolism, and elimination) profile are well-discussed in the literature. Cumulative literature suggests that PA has beneficial as well as harmful biological roles in humans and other animals. This study aimed to sketch a brief summary of PA’s beneficial and harmful pharmacological effects in test systems on the basis of existing literature reports. Literature findings propose that PA has anti-inflammatory and immunomodulatory, antidiabetic, anti-obesity, anticancer, and oocyte maturation effects. Although a high plasma PA-level mediated SLS remains controversial, it is evident to link it with Refsum’s disease and other peroxisomal enzyme deficiency diseases in humans, including RCDP and LD; ZHDA and Alzheimer’s disease; progressive ataxia and dysarthria; and an increased risk of some lymphomas such as LBL, FL, and NHL. PA exerts toxic effects on different kinds of cells, including neuronal, cardiac, and renal cells, through diverse pathways such as oxidative stress, mitochondrial disturbance, apoptosis, disruption of Na⁺/K⁺-ATPase activity, Ca²⁺ homeostasis, alteration of AChE and MAO activities, etc. PA is considered a cardiac biomarker in humans. In conclusion, PA may be one of the most important biometabolites in humans.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100120"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/e4/main.PMC10515296.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113722","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":"Ethnobotanical uses and phytochemical, biological, and toxicological profiles of Datura metel L.: A review","authors":"Tawhida Islam ,&nbsp;Iffat Ara ,&nbsp;Tariqul Islam ,&nbsp;Pankaj Kumar Sah ,&nbsp;Ray Silva de Almeida ,&nbsp;Edinardo Fagner Ferreira Matias ,&nbsp;Cícero Lucas Gomes Ramalho ,&nbsp;Henrique Douglas M. Coutinho ,&nbsp;Muhammad Torequl Islam","doi":"10.1016/j.crtox.2023.100106","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100106","url":null,"abstract":"<div><p>Datura metel L., a recognized poisonous plant in the Solanaceae family, is widely distributed in the world. Traditionally, D. metel is used in many diseases, including neurological and heart diseases; fever; catarrh; pain; diarrhea; skin diseases; chronic bronchitis; asthma; digestive disorders; and so on. It possesses many important phytochemicals that can be used to treat various types of diseases. This review aims at summarizing the traditional uses, phytochemical, biological, and toxicological profiles of D. metel based on the database reports. For this, an up-to-date (till March 20, 2023) search was made in the databases: PubMed, Google Scholar, Science Direct, Scopus, and MedLine, with relevant keywords for the published evidence. Findings suggest that the plant has many traditional uses, such as a cure for madness, epilepsy, psoriasis, heart diseases, diarrhea, mad dog bites, indigestion, etc. It possesses various important phytochemicals, including withanolides, daturaolone, datumetine, daturglycosides, ophiobolin A, baimantuoluoline A, and many others. D. metel has many important biological activities, including antioxidant, anti-inflammatory, anti-microbial, insecticidal, anti-cancer, anti-diabetic, analgesic, anti-pyretic, neurological, contraceptive, and wound healing capacity. In conclusion, the toxic plant, D. metel, can be considered a potential source of phyto-therapeutic lead compounds.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100106"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49777749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaga mushroom triterpenoids as adjuncts to minimally invasive cancer therapies: A review","authors":"Selina Plehn ,&nbsp;Sajeev Wagle ,&nbsp;H.P. Vasantha Rupasinghe","doi":"10.1016/j.crtox.2023.100137","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100137","url":null,"abstract":"<div><p>Cancer has become the second leading cause of death in the world. Integrative cancer therapy management is continuously evolving to enhance treatment outcomes. Chaga mushroom (<em>Inonotus obliquus</em>) is a parasitic fungus acclaimed to contain pharmaceutical and nutraceutical value in the fight against cancer. In particular, triterpenoid constituents derived from Chaga mushrooms have been recognized for their anti-cancer activity after distinguished cytotoxicity was repeatedly observed in cancer cells treated <em>in vitro</em> with lipophilic fractions of extract compared to aqueous ones. Studies that investigate the anti-cancer activity of Chaga mushroom triterpenoids are reviewed in this article to determine which cancer cell lines demonstrate the greatest susceptibility to them while highlighting the structure–activity relationships that are involved. Triterpenoid supplementation as an adjunct to cancer treatment may be a viable option as inotodiol and 3-β-22 α-dihydroxylanosta-8, 25-diene-24-one have been shown to exhibit anti-cancer activity similar to that of conventional drugs. Advances in addressing bioavailability challenges are also included in this review as studies include <em>in vivo</em> components.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100137"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X2300035X/pdfft?md5=873ac4385989441e838f58e4890cee10&pid=1-s2.0-S2666027X2300035X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136694410","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":"Characterization of the interferences of systemic azole antifungal drugs with adrenal steroid biosynthesis using H295R cells and enzyme activity assays","authors":"Marie-Christin Jäger,&nbsp;Friedrich L. Joos,&nbsp;Denise V. Winter,&nbsp;Alex Odermatt","doi":"10.1016/j.crtox.2023.100119","DOIUrl":"10.1016/j.crtox.2023.100119","url":null,"abstract":"<div><p>Azole antifungals, designed to inhibit fungal CYP51, have a liability to inhibit human CYP enzymes. Whilst drug-metabolizing CYPs are covered in preclinical safety assessment, those metabolizing endogenous bioactive molecules are usually not. Posaconazole and itraconazole were recently found to cause pseudohyperaldosteronism with hypokalemia and hypertension by inhibiting CYP11B1-dependent adrenal cortisol biosynthesis. Because this was overlooked in preclinical safety assessment, the present study tested whether applying adrenal carcinoma H295R cells could have predicted this liability and whether other systemic triazole antifungals interfere with adrenal steroidogenesis. Forskolin-stimulated H295R cells were exposed to systemic triazole antifungals that are currently used, and key adrenal steroids were quantified by UHPLC-MS/MS. To support the findings from the H295R model, activity assays for steroidogenic enzymes were performed. The analysis of the steroid profiles and product/substrate ratios predicted the CYP11B1 and CYP11B2 inhibition by posaconazole and itraconazole. Comparison of their steroid profiles allowed distinguishing their effects and suggested inhibition of adrenal androgen synthesis by posaconazole but not itraconazole, which was confirmed by CYP17A1 17,20-lyase activity measurements. In line with clinical observations, there was no evidence from these experiments for an inhibition of either CYP11B1/2 or CYP17A1 by voriconazole, fluconazole or isavuconazole. However, itraconazole and isavuconazole exerted an overall inhibition of steroidogenesis by a mechanism warranting further investigations. In conclusion, analyses of steroid profiles from the H295R assay and product/substrate ratios provide important information on the interference of a chemical with adrenal steroidogenesis and the underlying mechanism. This approach facilitates prioritization of further investigations, including enzyme expression and activity studies.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"5 ","pages":"Article 100119"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483343","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":"Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay","authors":"Daniel L. Villeneuve ,&nbsp;Michelle Le ,&nbsp;Monique Hazemi ,&nbsp;Adam Biales ,&nbsp;David C. Bencic ,&nbsp;Kendra Bush ,&nbsp;Robert Flick ,&nbsp;John Martinson ,&nbsp;Mackenzie Morshead ,&nbsp;Kelvin Santana Rodriguez ,&nbsp;Kelsey Vitense ,&nbsp;Kevin Flynn","doi":"10.1016/j.crtox.2022.100099","DOIUrl":"10.1016/j.crtox.2022.100099","url":null,"abstract":"<div><p>Concentrations at which global gene expression profiles in cells or animals exposed to a test substance start to differ significantly from those of controls have been proposed as an alternative point of departure for use in screening level hazard assessment. The present study describes pilot testing of a high throughput compatible transcriptomics assay with larval fathead minnows. One day post hatch fathead minnows were exposed to eleven different concentrations of three metals, three selective serotonin reuptake inhibitors, and four neonicotinoid-like compounds for 24 h and concentration response modeling was applied to whole body gene expression data. Transcriptomics-based points of departure (tPODs) were consistently lower than effect concentrations reported in apical endpoint studies in fish. However, larval fathead minnow-based tPODs were not always lower than concentrations reported to elicit apical toxicity in other aquatic organisms like crustaceans or insects. Random <em>in silico</em> subsampling of data from the pilot assays was used to evaluate various assay design and acceptance considerations such as transcriptome coverage, number of replicate individuals to sequence per treatment, and minimum number of differentially expressed genes to produce a reliable tPOD estimate. Results showed a strong association between the total number of genes for which a concentration response relationship could be derived and the overall variability in the resulting tPOD estimates. We conclude that, for our current assay design and analysis pipeline, tPODs based on fewer than 15 differentially expressed genes are likely to be unreliable for screening and that interindividual variability in gene expression profiles appears to be a more significant driver of tPOD variability than sample size alone. Results represent initial steps toward developing high throughput transcriptomics assays for use in ecological hazard screening.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100099"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/08/main.PMC9816907.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508170","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":"Zn and Se abrogate heavy metal mixture induced ovarian and thyroid oxido-inflammatory effects mediated by activation of NRF2-HMOX-1 in female albino rats","authors":"Boma F. Eddie-Amadi ,&nbsp;Anthonet N. Ezejiofor ,&nbsp;Chinna N. Orish ,&nbsp;Orish E. Orisakwe","doi":"10.1016/j.crtox.2022.100098","DOIUrl":"10.1016/j.crtox.2022.100098","url":null,"abstract":"<div><p>The thyroid is vital for the proper functioning of the female reproductive system since it regulates the metabolism and development of ovary. This is an evaluation of the essential trace elements ETE on the heavy metals mixture HMM mediated oxido-inflammatory effects in the ovary and thyroid of female albino rats. Five groups (5 female rats /group) were treated as follows for 60 days: Group 1: Deionized water only; Group 2: (Pb, Hg, Mn and Al); Group 3: HMM + ZnCl₂, 0.80 mg/kg; Group 4: HMM + Na₂SeO₃, 1.50 mg/kg; Group 5: HMM + ZnCl₂, 0.80 mg/kg and Na₂SeO₃, 1.50 mg/kg combined. On day 60 animals were euthanized, ovary and thyroid were harvested and used for, MDA, NO, antioxidants, TNF-α, IL-6, HMOX-1, Caspase-3, NF-KB, NRF2, HM and histopathology. There was significant bioaccumulation of Pb, Al, Hg and MN; elevated IL-6 and TNF-α, MDA and NO, caspase-3 and NRF2, NFKB and HMOX-1 with significant decrease in antioxidants in the HMM only group in comparison to the control. Co-treatment with ETE reversed most of these effects.</p><p>ETE may ameliorate HMM -induced ovarian and thyrotoxicity in female albino rats by blunting oxido-inflammatory activities.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"4 ","pages":"Article 100098"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520183","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}