Drug and Chemical Toxicology最新文献

{"title":"A 13-week oral toxicity and toxicokinetic study of cannabidiol in Sprague Dawley rats with a 4-week recovery period.","authors":"Wenhao Xia, Rendy Yanuar, Vivek Mandal, Kasper Renggli, Jenny Ho, Blaine Phillips, Gitte Nykjaer Nikolajsen, Sanne Skov Jensen, Heidi Ziegler Bruun, Julia Hoeng","doi":"10.1080/01480545.2025.2491544","DOIUrl":"https://doi.org/10.1080/01480545.2025.2491544","url":null,"abstract":"<p><p>Cannabidiol (CBD) is widely marketed as a health and wellness product. However, evidence for its effectiveness and safety remains limited. This study assessed the toxicity and toxicokinetic profile of CBD in Sprague Dawley rats over 13 weeks at low (5 mg/kg/day), mid (15 mg/kg/day), and high (150 mg/kg/day) doses, followed by a 4-week recovery period. Toxicokinetic analyses revealed no marked sex differences in systemic exposure to CBD or its metabolite 6-OH-CBD; however, female rats had slightly higher exposure to metabolites 7-OH-CBD and 7-COOH-CBD. Accumulation of CBD and its metabolites was observed following repeated oral administration of CBD. No CBD-related effects on mortality, clinical observations, or ophthalmoscopy were observed during the study. Higher food consumption was observed in rats treated with the high CBD dose group; however, this did not correlate with a statistically significant increase in body weight. A slightly higher fold increase in serum alanine aminotransferase (∼1.4-fold to 1.5-fold) was observed in the CBD high group, which was determined to be reversible. Histopathological analyses showed hepatocyte hypertrophy, but this effect was not accompanied by inflammatory changes or other microscopic lesions and resolved over the recovery period. Hypertrophy of pars distalis cells in pituitary gland and cortical cell vacuolation in adrenal glands were determined to be adaptive changes and reversible during the recovery period. The no-observed effect level was considered to be lower than the lowest tested dose (5 mg/kg/day) and no-observed adverse effect level to be the highest tested dose (150 mg/kg/day).</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962489","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":"Arylacetamides exhibit antiproliferative effects on non-transformed mammalian and vegetal cells and toxicity on crustaceans and fish embryos.","authors":"Kátia da Conceição Machado, Jurandy do Nascimento Silva, Débora Caroline do Nascimento Rodrigues, Stefânia Neiva Lavorato, João Marcelo de Castro E Sousa, Ana Amélia de Carvalho Melo-Cavalcante, Patrícia Canteri de Souza, Paulo César Meletti, Diego Sousa Moura, José Roberto de Oliveira Ferreira, Cesar Koppe Grisolia, Ricardo José Alves, Paulo Michel Pinheiro Ferreira","doi":"10.1080/01480545.2025.2492770","DOIUrl":"https://doi.org/10.1080/01480545.2025.2492770","url":null,"abstract":"<p><p>Non-clinical steps for development, validation and biosafety of new medicines and products comprises studies on cells, proteins, and animals. Herein, we evaluated the toxic activity of antitumoral 2-chloro-<i>N</i>-arylacetamides on eukaryotic dividing cells and animal replacement models. Firstly, the cytotoxicity of chloro (compound <b>2</b>), bromo (compound <b>3</b>) and nitro (compound <b>4</b>) acetamides was analyzed by fluorescent assays in fibroblasts. Next, toxicity was evaluated on <i>Allium cepa</i> meristematic cells and 48h-living <i>Artemia salina</i> larvae. Finally, embryos of <i>Danio rerio</i> (zebrafish) were exposed to the compound <b>2</b> (0.14 - 7.2 μg/mL) for 120 h exposure. All arylacetamides were cytotoxic on murine and human fibroblasts, with IC₅₀ values ranging from 1.2 μg/mL (5.6 µM = compound <b>4</b> on L-929) to 4.9 μg/mL (24 µM = compound <b>2</b> on MRC-5 cells), respectively, and inhibited root growth from 10 to 100 µg/mL, corroborated by mitotic index reduction and cell cycle arrest in interphase (<i>p</i> < 0.05) without clastogenic injuries. Compound <b>2</b> showed time- and concentration-dependent killing effects on zebrafish embryos. Its 24 h-acute toxicity at higher concentrations (1.93 and 7.2 μg/mL with 90% and 100% death) corroborated toxicity on aquatic <i>A. salina</i> organisms. After 96 h exposure at 0.52 μg/mL (2.55 µM), almost 100% of the embryos showed more than one lethal/sublethal morphological abnormality (<i>p</i> < 0.05). Then, all arylacetamides showed unspecific toxic effects, mainly the halogenated electrophile chloroacetamide. They present strong antimitotic action on vertebrate and vegetal cells, although such antiproliferative activity does not seem to be directly related to chromosomal damage inductions.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973007","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 the genotoxic and cytotoxic properties of teicoplanin: a combined laboratory and computational investigation.","authors":"Ahmet Ali Berber, Işıl Deniz Aliravci, Nihan Akinci Kenanoğlu, Şefika Nur Demir","doi":"10.1080/01480545.2025.2502446","DOIUrl":"https://doi.org/10.1080/01480545.2025.2502446","url":null,"abstract":"<p><p>In this study, the mutagenicity and carcinogenicity of the teicoplanin antibiotic were first investigated using the Vega Hub and Toxtree software through <i>in silico</i> prediction. The cytotoxic and genotoxic effects were evaluated using <i>in vitro</i> assays, including the mitotic index (MI), micronucleus (MN), nuclear division index (NDI), and Comet Assay (CA) in human lymphocytes. In the <i>in vitro</i> studies, both 24-hour and 48-hour exposures were conducted for MI, and teicoplanin significantly decreased MI compared to the control at all concentrations. In addition, a significant increase was detected in the MN frequency compared to the negative control at all concentrations. In the Comet assay, tail length significantly increased compared to the control at all concentrations except for 5.6 µg/mL, while tail moment and comet tail intensity significantly increased at all concentrations compared to the control. In conclusion, within the concentration range used in this study, teicoplanin was found to have cytotoxic and genotoxic effects.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988361","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":"Silymarin attenuates cobalt chloride-induced redox imbalance and cardio-renal dysfunctions in rats.","authors":"Temitayo Olabisi Ajibade, Okezi Michael Ohore, Oluwaseun Olarenwaju Esan, Bisi Olajumoke Adeoye, Ayodele Stephen Ake, Moses Olusola Adetona, Omolola Victoria Awoyomi, Olumayowa Olawumi Igado, Taiwo Olaide Oyagbemi, Adewunmi Victoria Adeogun, Ademola Adetokunbo Oyagbemi, Temidayo Olutayo Omobowale, Oluwafemi Omoniyi Oguntibeju, Evaristus Nwulia, Momoh Audu Yakubu","doi":"10.1080/01480545.2025.2499540","DOIUrl":"https://doi.org/10.1080/01480545.2025.2499540","url":null,"abstract":"<p><p>Silymarin is an extract of <i>Silybum marianum</i> that is used traditionally for the treatment of several diseases. This study sought to evaluate the protective effects of silymarin on cobalt chloride (CoCl₂)-induced cardio-renal toxicities in rats. Forty rats were randomly divided into four groups of 10 rats each: control; 300 mg/kg CoCl₂; CoCl₂ + 100 mg/kg silymarin; and 100 mg/kg silymarin only. All administrations were done orally. At the end of the experimental period (seven days), blood pressure parameters, markers of oxidative stress, antioxidant defense status, renal function test, histopathology and immunohistochemical expressions were evaluated on the heart and kidney tissues. Silymarin significantly (<i>p</i> < 0.05) altered CoCl₂-induced alterations in blood pressure parameters, antioxidants and markers of oxidative stress, blood urea nitrogen and creatinine. Histopathological evaluation revealed area of infiltration of the myocardium by inflammatory cells and hemorrhages in the kidney of rats exposed to CoCl₂ without silymarin treatment, but these lesions were absent in the control and silymarin groups. Increased immunohistochemical expression of cardiac troponin I and matrix metalloproteinase-2 (MMP-2) was observed in the cardiac tissues of rats exposed to CoCl₂ without silymarin treatment. The immunohistochemical expression of cystatin C was heightened, while that of angiotensin-converting enzyme 2 (ACE2) was attenuated in the CoCl₂ untreated group compared with the control and silymarin groups. In conclusion, silymarin effectively mitigated the toxic effects of CoCl₂ on the heart and kidney tissues of rats due to its ability to positively modulate the activities of endogenous antioxidants and neutralize reactive oxygen species in cardiac and renal systems.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973447","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":"Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats.","authors":"Kübra Asena Terim Kapakin, İsmail Bolat, Hatice İskender, Eda Dokumacioğlu, Esra Manavoğlu Kirman, Merve Bolat, Mevlana Gül","doi":"10.1080/01480545.2024.2391868","DOIUrl":"10.1080/01480545.2024.2391868","url":null,"abstract":"<p><p>Valproic acid (VPA) is a broad-spectrum drug that is now widely used as an antiepileptic. Although VPA has positive therapeutic effects, it also causes various toxic effects in tissues. Curcumin, a natural antioxidant found in ginger, has antibacterial and antiinflammatory activity. In this study, the toxic effects of VPA on brain, kidney, and liver tissues and the protective activity of curcumin against these effects were investigated. In this study, male Wistar-Albino rats were used. Rats were divided into 4 groups control, VPA, CUR, and CUR + VPA. Rats were administered intraperitoneal VPA and CUR intragastrically. In the study, MDA, SOD, IL-6, and IL-18 levels were measured by the ELISA method in rats. It was observed that VPA triggered oxidative stress and inflammation in tissues, while CUR administration positively regulated these parameters. Studies also showed that VPA increased the expressions of TNF-α and NF-kB in tissues, but CUR administration downregulated these expressions The findings revealed that CUR protects by preventing the oxidative stress and inflammation caused by VPA in the tissues and may be an important agent in reducing the side effects of this drug used as an antiepileptic.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"644-659"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105420","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":"Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract.","authors":"Laura E Ewing, Charles M Skinner, Mitchell R McGill, Stefanie Kennon-McGill, Kirsten Clement, Charles M Quick, Eric U Yee, D Keith Williams, Larry A Walker, Mahmoud A ElSohly, Bill J Gurley, Igor Koturbash","doi":"10.1080/01480545.2024.2388292","DOIUrl":"10.1080/01480545.2024.2388292","url":null,"abstract":"<p><p>Cannabidiol (CBD) is a major phytocannabinoid from <i>Cannabis sativa</i>. It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a novel human microphysiological system to emulate CRCE-induced hepatotoxicity and pharmacological properties demonstrated in animal models. For this purpose, C57BL6/J male mice were subjected to dosing with either 0, 61.5, 184.5, or 615 mg/kg of CRCE for 10 days. The liver-on-chip system, incorporating human primary hepatocytes, sinusoidal endothelial cells, as well as Kupffer and stellate cells was subjected to 0, 300, 1,200, or 4,400 ng/mL of CRCE (8 h exposure followed by 16 h washout) for 5 days. Administration of CRCE in mice resulted in nearly 4-fold elevations of plasma ALT at 615 mg/kg (<i>p</i> < 0.01) and a dose-dependent decrease in intrahepatic miR-122. Elevated levels of ALT, paralleled by decreased intrahepatic and increased effluent levels of miR-122, were also observed in the liver-on-chip, although these results were not statistically significant. Exposure to CRCE resulted in a robust and dose-dependent induction of key cytochrome P450 enzymes, namely <i>Cyp1a2</i>, <i>Cyp2b6</i> (<i>CYP2B10</i>), <i>Cyp2e1</i>, and <i>Cyp2c9</i> (<i>CYP2C19</i>) in both mouse livers and liver-on-chip. The results of this study demonstrate the congruence between the responses observed in mouse and human liver-on-chip experimental systems and provide evidence of the potential microphysiological systems hold for translating animal data into clinical practice.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"578-585"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ivermectin-induced toxicity in HepG2 cells and the protective effect of tetrahydrocurcumin and vitamin C.","authors":"Camila Araújo Miranda, João Rodolfo Domingues Mansano, Fábio Erminio Mingatto","doi":"10.1080/01480545.2024.2389954","DOIUrl":"10.1080/01480545.2024.2389954","url":null,"abstract":"<p><p>Ivermectin (IVM) is a semi-synthetic antiparasitic derived from abamectin, one of the natural avermectins. The liver promotes metabolism and excretion of IVM, representing a risk of toxicity to this organ. The use of antioxidants to alleviate damage caused by chemicals has been increasingly studied. Thus, the aim of this study was to evaluate the effects of IVM on HepG2 cells to elucidate the mechanisms related to its toxicity and the possible protection provided by tetrahydrocurcumin (THC) and vitamin C. HepG2 cells were treated with IVM (1-25 μM) for 24 and 48 h. IVM was cytotoxic to HepG2 cells, denoted by a dose-dependent decrease in cell proliferation and metabolic activity. In addition, IVM induced damage to the cell membrane at all tested concentrations and for both incubation times. IVM significantly decreased the mitochondrial membrane potential from concentrations of 5 μM (24 h) and 1 μM (48 h). Additionally, IVM showed a time- and dose-dependent decrease in cellular adenosine triphosphate levels. The levels of reduced glutathione were decreased in a time- and dose-dependent manner, while IVM stimulated the production of reactive oxygen and nitrogen species (RONS) at all tested doses, reaching rates above 50% following treatment at 7.5 μM (24 h) or 5 μM (48 h). Treatment with THC (50 μM) and vitamin C (50 μM) protected against IVM-induced cytotoxicity and RONS production. These results suggest that oxidative damage is involved in IVM-induced toxicity in HepG2 cells, and that THC and vitamin C can mitigate the toxic effects caused by the compound.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"595-605"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999598","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":"Exploring health beneficial effects of poisonous mushroom <i>Paxillus involutus</i> Batsch Fr.","authors":"Jovana Petrović, Jasmina Glamočlija, Stefana Cvetković, Biljana Nikolić, Uroš Gašić, Dragana Robajac","doi":"10.1080/01480545.2024.2412776","DOIUrl":"10.1080/01480545.2024.2412776","url":null,"abstract":"<p><p>In the present study, phenolic and flavonoid composition and biological properties of methanolic extract of wild growing <i>Paxillus involutus</i> collected in Serbia have been investigated. Ellagic acid was the most abundant phenolic compound (34.92 µg g-¹), followed by 5-O-caffeoylquinic acid (4.51 µg g-¹), whereas isoorientin was the most abundant flavonoid (3.42 µg g-¹). <i>P. involutus</i> turned out to be a rich source of phenolic compounds (74.67 mg GAE g-¹ d.w.), whereas total flavonoid content was significantly lower (4.05 mg QE g-¹ d.w.). As for the various investigated biological activities, methanolic extract exerted high level of antioxidant, antimicrobial and antibiofilm activities. The highest antioxidative potential was measured by TAC (350 TE mg g-¹ d.w.), whereas evaluation of antimicrobial properties showed selective antimicrobial potential toward tested pathogenic microorganisms, with resistant strain of <i>E. coli</i> being the most susceptible to the activity of the extract (MIC 0.08 mg mL-¹, MBC 0.16 mg mL-¹). Furthermore, methanolic extract of <i>P. involutus</i> demonstrated genotoxicity, severe hemolysis effects and selective cytotoxicity against colon cancer cells. From the obtained data, it may be concluded that investigated mushroom albeit being toxic for human consumption, may be considered as a source of highly bioactive components with potential application in drug development.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"616-626"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460502","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":"Mitigating aluminum chloride-induced toxicity in <i>Drosophila melanogaster</i> with peptide fractions from <i>Euphorbia</i> species.","authors":"Jola-Jesu Mercy Akano, Zainab Abiodun Molik, Amos Olalekan Abolaji, Omonike Oluyemisi Ogbole","doi":"10.1080/01480545.2024.2421916","DOIUrl":"10.1080/01480545.2024.2421916","url":null,"abstract":"<p><p>This study assessed the antioxidative and protective effects of peptide extracts from selected <i>Euphorbia</i> species on Aluminum Chloride (AlCl₃)-induced toxicity in <i>Drosophila melanogaster. Euphorbia humifusa</i> (EHU), <i>Euphorbia hirta</i> (EHI), and <i>Euphorbia graminae</i> (EHG) were screened for bioactive peptides. The crude peptide extract and partially purified peptide fractions of all the plants were subjected to preliminary antioxidants activities through 2, 2-diphenyl-1-picrylhyhdrazyl (DPPH), and nitric oxide (NO) scavenging activities. The most active peptide fraction was subjected to biochemical studies using <i>Drosophila melanogaster.</i> Flies were treated with AlCl₃ (100 mg/kg diet), peptide fraction (5 and 10 mg/kg diet), and cotreatment of AlCl₃ and the fraction, respectively. After treatment, flies were homogenized for the determination of total thiol and Glutathione (non-protein thiol) content, catalase and Glutathione-S-transferase activities, and nitric oxide (nitrite/nitrate) and hydroperoxide levels. The antioxidant screening revealed that the peptide fraction from <i>Euphorbia humifusa</i> (PEHU) was the most significant compared to the control (ascorbic acid). The PEHU (5 and 10 mg/kg diet) maintained the redox status of the flies in the biochemical study. The PEHU significantly counteracted AlCl₃-induced reduction in antioxidants (catalase, GST, GSH and Total thiol), increased nitric oxide levels, and acetylcholinesterase activity and prevented behavioral deficits flies. Hence, the peptide fraction of <i>Euphorbia humifusa</i> may shield against the life-threatening effects of free radicals associated with aluminum chloride toxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"687-696"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582191","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":"The effect of cut sizes and pH of tobacco leaf in smokeless tobacco products on the pharmacokinetics of nicotine.","authors":"Ya'ning Fu, Hongjuan Wang, Yingyan Li, Pengpeng Yu, Yue Su, Wanwan Ma, Shulei Han, Yushan Tian, Huan Chen, Hongwei Hou","doi":"10.1080/01480545.2024.2431862","DOIUrl":"10.1080/01480545.2024.2431862","url":null,"abstract":"<p><p>The absorption of nicotine from smokeless tobacco products (STPs) in humans is affected by various factors, including nicotine content, flavoring compounds, cutting format, tobacco cut sizes, and pH. In this study, participants were asked to use STP 1 for a specific period, after which the nicotine content was measured before and after use to determine the release rate using the <i>Weibull model</i>. Blood samples were collected from participants after 30 min of using STP 1 to assess nicotine pharmacokinetics. Additionally, guinea pigs were administered four types of STPs with varying pH levels, and tobacco cut sizes, but with identical nicotine content on the oral mucosa to evaluate nicotine pharmacokinetics. The human results showed that nicotine in STP was quickly released in the mouth, reaching 73.66% within 30 min. Plasma nicotine concentration in guinea pigs and human participants were comparable following STP use. Guinea pigs exposed to STPs with smaller tobacco cut sizes or higher pH absorbed more nicotine and metabolized it more slowly. The findings suggest that pH and cut size of STPs are key factors affecting nicotine absorption, while the impact of flavoring agents and other components on nicotine absorption remains to be determined.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"660-667"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750336","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}