Current Research in Toxicology最新文献

{"title":"In vitro-in silico study on the influence of dose, fraction bioactivated and endpoint used on the relative potency value of pyrrolizidine alkaloid N-oxides compared to parent pyrrolizidine alkaloids","authors":"Yasser Alhejji ,&nbsp;Frances Widjaja ,&nbsp;Shenghan Tian ,&nbsp;Thomas Hoekstra ,&nbsp;Sebastiaan Wesseling ,&nbsp;Ivonne M.C.M. Rietjens","doi":"10.1016/j.crtox.2024.100160","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100160","url":null,"abstract":"<div><p>Pyrrolizidine alkaloids (PAs) and their N-oxides (PA-N-oxides) are phytotoxins found in food, feed and the environment. Yet, limited data exist from which the relative potency of a PA-N-oxide relative to its corresponding PA (REP_{PANO to PA}) can be defined. This study aims to investigate the influence of dose, fraction bioactivated and endpoint on the REP_{PANO to PA} of a series of pyrrolizidine N-oxides using in vitro-in silico data and physiologically based kinetic (PBK) modeling. The first endpoint used to calculate the REP_{PANO to PA} was the ratio of the area under the concentration–time curve of PA resulting from an oral dose of PA-N-oxide divided by that from an equimolar dose of PA (Method 1). The second endpoint was the ratio of the amount of pyrrole-protein adducts formed under these conditions (Method 2). REP_{PANO to PA} values appeared to decrease with increasing dose, with the decrease for Method 2 already starting at lower dose level than for Method 1. At dose levels as low as estimated daily human intakes, REP_{PANO to PA} values amounted to 0.92, 0.81, 0.78, and 0.68 for retrorsine N-oxide, seneciphylline N-oxide, riddelliine N-oxide and senecivernine N-oxide, respectively, and became independent of the dose or fraction bioactivated, because no GSH depletion, saturation of PA clearance or PA-N-oxide reduction occurs. Overall, the results demonstrate the strength of using PBK modeling in defining REP_{PANO to PA} values, thereby substantiating the use of the same approach for other PA-N-oxides for which in vivo data are lacking.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100160"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000136/pdfft?md5=558a8507f5b1e3044fad14e8be8c39a4&pid=1-s2.0-S2666027X24000136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140052433","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":"Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre parameters to the key characteristics of carcinogens: A comprehensive model inspiring asbestos-induced cancer prevention strategies","authors":"Alessandro F. Gualtieri ,&nbsp;Erika Ferrari ,&nbsp;Luca Rigamonti ,&nbsp;Barbara Ruozi ,&nbsp;Serena Mirata ,&nbsp;Vanessa Almonti ,&nbsp;Mario Passalacqua ,&nbsp;Stefania Vernazza ,&nbsp;Silvia Di Valerio ,&nbsp;Giovanni Tossetta ,&nbsp;Salvatore Vaiasicca ,&nbsp;Antonio D. Procopio ,&nbsp;Francesca Fazioli ,&nbsp;Daniela Marzioni ,&nbsp;Armanda Pugnaloni ,&nbsp;Sonia Scarfì","doi":"10.1016/j.crtox.2024.100202","DOIUrl":"10.1016/j.crtox.2024.100202","url":null,"abstract":"<div><h3>Background</h3><div>Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects <em>in vivo</em> leading to carcinogenesis.</div></div><div><h3>Methods</h3><div><em>In vitro</em> toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite. The analysis of the <em>in vitro</em> data allowed us to assess the major fibre parameters responsible for alterations in the key characteristics of carcinogens for each investigated fibre and the intensity of their effect.</div></div><div><h3>Results</h3><div>Crystal habit and density of the fibres affect exposure but are not major parameters contributing to the KCs. For chrysotile, besides length, we found that fibre parameters that greatly contribute to the KCs are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are the fibre length, iron content and related parameters like the ferrous iron content, iron nuclearity, transition metals content and zeta potential.</div></div><div><h3>Conclusions</h3><div>The results of our study can be a starting point for developing personalized cancer screening and prevention strategies as long as the nature of the fibre of the exposed patient is known. We can speculate on a future personalized prevention therapy targeting the fibres with surface-engineered nanocarriers with active complexes that are selective for the surface charge of the fibres. For chrysotile, a complex with deferasirox that can chelate Fe²⁺ and deferoxamine that preferentially chelates Fe³⁺ is proposed with the anchorage to the silica chrysotile surface driven by aspartic acid. For crocidolite, deferiprone chelating both Fe³⁺ and Fe²⁺ combined with lysine to attract the silica crocidolite surface is proposed.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100202"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698303","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":"Lactational exposure of human infants to metal(loid)s in Sub-Saharan Africa and Mediterranean Europe: A systematic review and meta-analysis","authors":"Amarachi Paschaline Onyena ,&nbsp;Onyinyechi Bede-Ojimadu ,&nbsp;Taagbara Jolly Abaate ,&nbsp;Dokuboba Amachree ,&nbsp;Chiara Frazzoli ,&nbsp;Opeyemi M. Folorunso ,&nbsp;Beatrice Bocca ,&nbsp;Orish E. Orisakwe","doi":"10.1016/j.crtox.2024.100201","DOIUrl":"10.1016/j.crtox.2024.100201","url":null,"abstract":"<div><div>Breast milk, a fundamental component of infant nutrition, may serve as a reservoir for various metal(loid)s, which could pose significant health risks to infants of mothers exposed to toxic metals. Human exposure levels to metal(loid)s vary across regions, influenced by differences in diet, lifestyle, and environmental factors. This systematic review compares metal(loid) concentrations in breast milk from Sub-Saharan Africa (SSA) and Mediterranean Europe (Med. Europe), identifying key determinants of exposure. PubMed, Scopus, and Google Scholar were searched for articles reporting metal concentrations in human breast milk samples from SSA and Med. Europe. Weighted mean concentrations were estimated and compared between the two regions. Twenty-five studies from SSA and seventeen from Med. Europe were included in the review. Mean concentrations of cadmium (12.38 ± 1.21 µg/L vs 0.22 ± 0.51 µg/L; p &lt; 0.0001), lead (14.96 ± 8.10 µg/L vs 1.16 ± 4.00 µg/L; p &lt; 0.0001), and mercury (2.01 ± 1.37 µg/L vs 0.95 ± 4.32 µg/L; p = 0.008) were higher in breast milk samples from SSA than Med. Europe. Conversely, breast milk samples from SSA had lower concentrations of selenium (7.38 ± 2.67 µg/L vs 13.09 ± 16.89 µg/L; p &lt; 0.0001) and iron (138.78 ± 106.33 µg/L vs 371.97 ± 446.74 µg/L; p &lt; 0.0001) than those from Med. Europe. Key determinants of metal(loid)s levels in breast milk included maternal smoking, dietary patterns, and environmental exposure. There is an urgent need for effective interventions and policies to reduce metals exposure, particularly in SSA, to safeguard maternal and infant health.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100201"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698305","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":"Sesquiterpene-evoked phytochemical toxicity in PC12 neuronal cells reveals a variable degree of oxidative stress and alpha-tocopherol and glutathione-dependent protection","authors":"John Staton Laws III,&nbsp;Scott D. Smid","doi":"10.1016/j.crtox.2023.100144","DOIUrl":"https://doi.org/10.1016/j.crtox.2023.100144","url":null,"abstract":"<div><p>Phytochemicals are often promoted generally as antioxidants and demonstrate variable levels of reactive oxygen species (ROS) sequestration in vitro, which attributes to their neuroprotective bioactivity. Sesquiterpenes from cannabis and essential oils may demonstrate bifunctional properties towards cellular oxidative stress, possessing pro-oxidant activities by generating ROS or scavenging ROS directly. Sesquiterpenes can also oxidize forming sesquiterpene oxides, however the relative contribution they make to the bioactivity or cytotoxicity of complex botanical extracts more generally is unclear, while selected cannabis-prevalent terpenes such as β-caryophyllene may also activate cannabinoid receptors as part of their biological activity. In the present study, we investigated selected sesquiterpenes β-caryophyllene and humulene and their oxidized forms (β-caryophyllene oxide and zerumbone, respectively) against established antioxidants (ascorbic acid, α-tocopherol, and glutathione) and in the presence of cannabinoid receptor 1 and cannabinoid receptor 2 antagonists, to gain a better understanding of the molecular and cellular mechanisms of neuroprotection versus neurotoxicity in semi-differentiated rat neuronal phaeochromocytoma (PC12) cells. Our results demonstrate that the sesquiterpenes β-caryophyllene, humulene and zerumbone possess concentration-dependent neurotoxic effects in PC12 cells. Both β-caryophyllene- and humulene-evoked toxicity was unaffected by CB1 or CB2 receptor antagonism, demonstrating this occurred independently of cannabinoid receptors. Both glutathione and α-tocopherol were variably able to alleviate the concentration-dependent loss of PC12 cell viability from exposure to β-caryophyllene, humulene and zerumbone. During 4-hour exposure to sesquiterpenes only modest increases in ROS levels were noted in PC12 cells, with glutathione co-incubation significantly inhibiting intracellular ROS production. However, significant increases in ROS levels in PC12 cells were demonstrated during 24-hour incubation with either antioxidants or sesquiterpenes individually, and with additive toxicity exhibited in combination. Overall, the results highlight a concentration-dependent profile of sesquiterpene neurotoxicity independent of cannabinoid receptors and dissociated from the formation of reactive oxygen species as a marker or correlate to the loss of cell viability.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100144"},"PeriodicalIF":3.3,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X23000427/pdfft?md5=815a2b37a0d18927d6e43c4fbf6bf55e&pid=1-s2.0-S2666027X23000427-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138739197","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 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}