XenobioticaPub Date : 2025-02-01Epub Date: 2025-04-28DOI: 10.1080/00498254.2025.2494649
R Montes de Oca Porto, D Martinez Brito, O Terrero Serrano, M T Correa Vidal
{"title":"Study of the urinary metabolites of 17ɑ-methyl-19-nortestosterone in human using gas chromatography - mass spectrometry. Preliminary results.","authors":"R Montes de Oca Porto, D Martinez Brito, O Terrero Serrano, M T Correa Vidal","doi":"10.1080/00498254.2025.2494649","DOIUrl":"10.1080/00498254.2025.2494649","url":null,"abstract":"<p><p>17ɑ-methyl-19-nortestosterone (MNT), a steroid prohibited in sport, has been marketed since the 1990s, however their use is increasingly, mainly because it is contained in nutritional supplements. The study of the metabolism of the prohibited substances for athletes allows to identify new metabolites that could increase the veracity of the results. This work studied preliminary the in-vivo metabolism of MNT.The study was conducted after a single oral administration dose using the simple quadrupole mass spectrometry coupled to gas chromatography and considering the steroids classic metabolic reactions.Nine MNT metabolites were detected in urine. Mass spectra and fragmentation patterns were proposed for each metabolite. In addition to MNT, the detection of four metabolites corroborated what is described in the specialised literature. However, to our knowledge, four other metabolites have not been explicitly described. According to the time-course, three metabolites were still detected at 96-, 84- and 72-hours port-administration. These detection windows can increase by using other instrumentations such as a triple quadrupole mass spectrometer with multiple reaction monitoring acquisition mode.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"61-70"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030343","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-04-21DOI: 10.1080/00498254.2025.2493619
Daniel A Torres-García, Victor E Balderas-Hernández, Ana P Barba de la Rosa, Antonio De Leon-Rodriguez
{"title":"Diisononyl phthalate down-regulates the expression of antioxidant genes <i>NFE2L2</i>, <i>TXN</i>, and <i>TXNRD2</i>, while diethyl-hexyl terephthalate up-regulates their expression including <i>SOD-1</i>.","authors":"Daniel A Torres-García, Victor E Balderas-Hernández, Ana P Barba de la Rosa, Antonio De Leon-Rodriguez","doi":"10.1080/00498254.2025.2493619","DOIUrl":"10.1080/00498254.2025.2493619","url":null,"abstract":"<p><p>Phthalates, widely utilised as plasticisers to enhance the flexibility of rigid materials like polyvinyl chloride, are known for their endocrine-disrupting properties and cytotoxic effects.This study investigated the impact of Diisononyl phthalate (DINP) and Diethyl-hexyl terephthalate (DEHT) on human endothelial cells (EA.hy926).The assessment focused on cell viability, reactive oxygen species (ROS) production, and the antioxidant-responsive genes expression (<i>NFE2L2</i>, <i>SOD1</i>, <i>TXN</i>, and <i>TXNRD2</i>) following exposure to varying 1, 10, and 100 µg/mL of DINP or DEHT.Cell viability was determined using MTT and lactate dehydrogenase (LDH) release assays. ROS were measured using the DCFDA assay.Gene expression analysis was conducted <i>via</i> qRT-PCR after 48 h of exposure. Results revealed that DINP 100 µg/mL significantly reduced cell viability at 11 and 17% at 48 and 72 h, respectively, whereas increased LDH release by 69% at 48 h. ROS levels also rose by 19-30%, accompanied by down-regulation of <i>NFE2L2</i>, <i>TXN</i>, and <i>TXNRD2</i>.Conversely, DEHT had no adverse effect on cell viability or LDH levels but elevated ROS production (11-14%) and induced up-regulation of antioxidant genes, including <i>SOD1</i>.The findings indicate that DINP exposure could negatively affect the cellular antioxidant response, whereas DEHT leads to up-regulation of antioxidant genes without detrimental effects on viability.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"110-120"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050898","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-04-24DOI: 10.1080/00498254.2025.2494655
Ana Elizia Cunha Carvalho, Ana Clara Rodrigues de Oliveira, Francisco de Sousa Holanda, Eduardo Libanio Reis Santos, Jeffesson de Oliveira-Lima
{"title":"Benzophenone-3 (oxybenzone) in zebrafish: histopathological and oxidative stress analysis.","authors":"Ana Elizia Cunha Carvalho, Ana Clara Rodrigues de Oliveira, Francisco de Sousa Holanda, Eduardo Libanio Reis Santos, Jeffesson de Oliveira-Lima","doi":"10.1080/00498254.2025.2494655","DOIUrl":"10.1080/00498254.2025.2494655","url":null,"abstract":"<p><p>Benzophenone-3, commonly known as oxybenzone, is an organic compound widely used in sunscreens and personal care products for protection against UVA and UVB rays. Due to its environmental persistence and potential toxicity, this study evaluated the effects of BP-3 at an environmentally relevant concentration (1 µg/L) on the gills, kidney, and antioxidant system of zebrafish (<i>Danio rerio</i>).Adult male zebrafish were randomly distributed into three groups, each with three replicates (n = 10 per group): water control, solvent control, and 1 µg/L BP-3, using a static exposure system for 96 hours. After the experiment, histopathological analyses of the gills and kidneys were performed, along with biochemical assessments of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT).Exposure to BP-3 resulted in significant histopathological alterations in the gills, including vascular congestion, epithelial detachment, edoema, and lamellar aneurysm, indicating severe damage to respiratory function. In the kidneys, glomerular capillary dilation, tubular cell vacuolisation, and focal necrosis were observed, suggesting renal dysfunction. Biochemical analyses revealed impairment of the antioxidant defense system: in the gills, SOD activity decreased, while CAT remained unchanged, indicating oxidative stress accumulation. In the kidneys, SOD activity significantly increased, while CAT decreased, suggesting enzymatic imbalance and cumulative oxidative damage.These results demonstrate that BP-3, even at low concentrations, induces significant histopathological and biochemical alterations in the gills and kidneys of <i>D. rerio</i>, highlighting its potential to compromise organ function and antioxidant defences. These findings underscore the need for stricter regulation of BP-3 release into aquatic environments to mitigate its ecotoxicological impacts and protect aquatic biodiversity.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"71-77"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043390","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-01-20DOI: 10.1080/00498254.2025.2453983
Kouji Tagawa, Yoshihiro Maruo
{"title":"Dolutegravir metabolism: impact of genetic variations on uridine diphosphate glucuronosyltransferase subfamilies.","authors":"Kouji Tagawa, Yoshihiro Maruo","doi":"10.1080/00498254.2025.2453983","DOIUrl":"10.1080/00498254.2025.2453983","url":null,"abstract":"<p><p>Dolutegravir (DTG) is a key drug used to treat human immunodeficiency virus type-1 (HIV-1) infections. Adverse events (AEs) of DTG treatment, including headache, anxiety, depression, insomnia, and abnormal dreams, are influenced by sex, body weight, age, and serum bilirubin levels. DTG is mainly metabolised by members of the uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As), especially UGT1A1.Some studies suggest a relationship between <i>UGT1A1</i> variants and AEs. The aim of this study was to identify UGT1A isoforms that exhibit DTG glucuronidation activity and determine the relationship between <i>UGT1A</i> variants and DTG glucuronidation <i>in vitro</i>.UGT1A1, UGT1A3, UGT1A9, and UGT1A10 exhibited DTG glucuronidation activity, of which UGT1A1 was the most active. Furthermore, variants of these isoforms showed decreased DTG glucuronidation activity. The different variants of <i>UGT1A</i>s, such as UGT1A1.6, UGT1A1.7, UGT1A1.35, UGT1A1.63, UGT1A3.5, UGT1A9.2, UGT1A10M59I, and UGT1A10T202I, showed reduced glucuronidation activity towards DTG in comparison with the wild-type <i>UGT1A</i>s.This study elucidates the relationship between <i>UGT1A</i> variants and the levels of glucuronidation associated with each variant.Checking for <i>UGT1A</i>s may be helpful in predicting potential toxicities and adverse effects related to DTG treatment.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"43-50"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012803","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-05-08DOI: 10.1080/00498254.2025.2494651
Binglei Yuan
{"title":"Effectiveness of pain care intervention combined with traditional Chinese medicine care in the perioperative care of patients with urinary stones.","authors":"Binglei Yuan","doi":"10.1080/00498254.2025.2494651","DOIUrl":"10.1080/00498254.2025.2494651","url":null,"abstract":"<p><p>The study investigated the effectiveness of pain care intervention combined with traditional Chinese medicine (TCM) care in the perioperative care of patients with urinary stones.Pain and urinary function recovery before and after postoperative care intervention, and Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) scores before and after care intervention in the two groups were compared. First anal discharge time, catheter retention time, first out of bed activity time, the total number of hospital days, and complications were observed in both groups after surgery, and the satisfaction scores of patients in both groups with the perioperative care were recorded.Compared with the control group, the observation group showed lower first anal discharge time, catheter retention time, first out of bed activity time, the total number of hospital days, and the incidence of complications after surgery, and the patients were more satisfied with the care.Pain care intervention combined with TCM care is beneficial in reducing postoperative pain in patients undergoing urinary stone surgery, speeding up the recovery of urinary function, improving sleep quality, anxiety, and depression, and reducing the incidence of complications.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"78-84"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038311","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-03-19DOI: 10.1080/00498254.2025.2465237
Elena A Yanovskaya, Galina A Frelikh, Alexander P Lakeev, Vera I Smolyakova, Galina A Chernysheva
{"title":"Bioavailability and dose proportionality of a highly lipophilic phenolic antioxidant.","authors":"Elena A Yanovskaya, Galina A Frelikh, Alexander P Lakeev, Vera I Smolyakova, Galina A Chernysheva","doi":"10.1080/00498254.2025.2465237","DOIUrl":"10.1080/00498254.2025.2465237","url":null,"abstract":"<p><p>IBP (2,6-diisobornyl-4-methylphenol) is a camphene derivative with unique pharmacological properties and low toxicity. It exhibits pronounced antioxidant and membrane-protective effects, making it a promising cardio- and neuroprotector.The aim of the study was investigating the pharmacokinetics of IBP in rats after intravenous (1 mg/kg) and oral administration at three doses (10, 25, 50 mg/kg). Specifically, we focused on assessing the bioavailability and dose proportionality following oral administration.Blood samples were collected <i>via</i> a jugular vein catheter, and plasma samples were analysed using a validated HPLC-MS/MS method. The calculation of pharmacokinetic parameters was performed by both non-compartmental and compartmental approaches. The proposed dosage form for intravenous administration was a multicomponent mixture containing <i>N</i>-methyl-2-pyrrolidone.Concentration of IBP in the body after intravenous administration decreased over time, exhibiting bi-exponential decay kinetics. IBP reached peak concentrations immediately and was rapidly distributed into the peripheral compartment after intravenous administration. The systemic exposure after oral administration was proportional to the dose. The calculated absolute oral bioavailability of IBP was no more than 20%.The value of the average half-life of IBP after intravenous administration exceeded similar values after oral administration by 1.5-1.6 times.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"51-60"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442192","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}
XenobioticaPub Date : 2025-02-01Epub Date: 2025-03-17DOI: 10.1080/00498254.2025.2475501
Getahun Befirdu Abza, Kristof De Vos, Pieter Annaert
{"title":"Inhibition of ABC transporters by sorafenib and lenvatinib: implications for drug-induced cholestasis.","authors":"Getahun Befirdu Abza, Kristof De Vos, Pieter Annaert","doi":"10.1080/00498254.2025.2475501","DOIUrl":"10.1080/00498254.2025.2475501","url":null,"abstract":"<p><p>Sorafenib and lenvatinib are systemic treatments for hepatocellular carcinoma. They often exhibit high intersubject pharmacokinetic variability and can cause drug-induced liver injury, yet the underlying mechanisms are poorly understood. Inhibition of some ATP-binding cassette (ABC) transporters, such as bile salt export pump (BSEP; <i>ABCB11</i>) and multidrug resistance-associated protein 2 (MRP2; <i>ABCC2</i>), which are involved in bile acid disposition, may lead to cholestatic liver injury.In this study, we investigated the inhibitory effects of sorafenib and lenvatinib on selected ABC transporters in membrane vesicles and sandwich-culture human hepatocytes (SCHH) using fluorescent probe substrates.The BSEP-mediated tauro-nor-THCA-24-DBD uptake was inhibited by sorafenib, with half-maximal inhibitory concentrations (IC<sub>50</sub>) of 30.1 μM. Transport of Lucifer yellow by BCRP was strongly inhibited by sorafenib (IC<sub>50</sub> = 2.9 μM). Only sorafenib affected MRP2 activity (IC<sub>50</sub> = 15.6 µM). Both drugs showed comparable inhibition potency on P-gp with IC<sub>50</sub> values of 12.4 μM for sorafenib and 13.9 μM for lenvatinib. Unlike lenvatinib, sorafenib decreased the biliary excretion of tauro-nor-THCA-24-DBD, a probe substrate of BSEP, in SCHH by over 40%.In conclusion, sorafenib exhibited a more pronounced inhibition of ABC transporters, including BCRP, BSEP and MRP2, than lenvatinib, which could contribute to cholestatic liver injury.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"99-109"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651035","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":"<i>In vivo</i> inhibition of CYP2E1 fails to reduce pulegone-induced liver injury in mice.","authors":"Liwen Huan, Yahong Zhang, Wenwen Liu, Hongyu Lu, Cai Zhang, Runting Yin, Zhen Ouyang, Yuan Wei","doi":"10.1080/00498254.2025.2493620","DOIUrl":"10.1080/00498254.2025.2493620","url":null,"abstract":"<p><p>Pulegone, an active component of the Chinese herb <i>Mentha haplocalyx</i> Briq., is primarily found in <i>Mentha arvensis</i> oil. It exerts toxic effects on the liver, nervous system, and kidneys, and its excessive intake leads to various adverse reactions and potentially fatal outcomes. CYP2E1 is considered the major metabolic enzyme that produces toxic metabolites of pulegone, which in turn cause toxicity in hepatocytes.This study aimed to establish a method for treating pulegone-induced acute liver injury <i>via in vivo</i> inhibition of CYP2E1 in mice.Acute liver toxicity was observed in mice intraperitoneally injected with 200 mg/kg pulegone, manifested as elevated serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), disorganisation of the hepatic lobular structure, degeneration of hepatocytes, karyopyknosis, apoptosis, and upregulation of inflammatory factors. Hepatic CYP2E1 expression was inhibited by the delivery of siRNA in lipid nanoparticles in mice.However, experimental results showed that si-<i>Cyp2e1</i> LNPs could not ameliorate acute liver injury induced by pulegone. Interestingly, bicyclol could attenuate that liver injury in mice, which may be related to the inhibition of hepatocyte apoptosis.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"121-130"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047841","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}
XenobioticaPub Date : 2025-01-01Epub Date: 2025-01-22DOI: 10.1080/00498254.2024.2448979
Fred Farris, Ayda Awaness, Joe Su
{"title":"Inorganic mercury pharmacokinetics in man: a hybrid model.","authors":"Fred Farris, Ayda Awaness, Joe Su","doi":"10.1080/00498254.2024.2448979","DOIUrl":"10.1080/00498254.2024.2448979","url":null,"abstract":"<p><p>A four-compartment model is presented that simulates inorganic mercury [Hg(II)] pharmacokinetics in blood, tissue, and excreta over a 70-day period. Simulations are validated against data collected from five human subjects, and previously analyzed.In the model, two compartments simulate Hg(II) in blood: one for mobile-Hg(II) and the other for immobile-Hg(II). Two corresponding compartments simulate Hg(II) in tissue. Mobile-Hg(II) represents Hg(II) available for transport across cell membranes. Immobile-Hg(II) represents Hg(II) that is not easily transported.Following dosing, blood total-Hg(II) droped rapidly in all subjects. Blood mobile-Hg(II) also droped rapidly with a concomitant rise in blood immobile-Hg(II). For four subjects, immobile-Hg(II) became the dominant Hg(II) species in blood by day 4. For subject five, mobile-Hg(II) remained dominant in blood for the study duration.Tissue mobile-Hg(II) declined rapidly for four of the subjects, with a simultaneous rapid rise in tissue immobile-Hg(II). In subject 5, tissue mobile-Hg(II) declined linearly, and immobile-Hg(II) accumulated slowly in tissue. For all subjects, tissue mobile-Hg(II) is the primary source of fecal Hg(II). The major source for Hg(II) excreted into the urine is immobile-Hg(II) from tissue.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"4-15"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955931","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}