Study on the transport and internalization mechanism of dietary supplement nattokinase in the small intestine using animal and Caco-2 cell monolayer models
This study first evaluated the preventive effect of supplementing low dose (4000 FU (Fibrin Unit)/kg, n = 6), medium dose (8000 FU/kg, n = 6), and high dose (12000 FU/kg, n = 6) of nattokinase on carrageenan induced thrombosis in mice. Subsequently, we used the rat gut sac model, ligated intestinal loop model, and Caco-2 cell uptake model to study the intestinal transport mechanism of NK.4. Results indicate that NK is a moderately absorbed biomolecule whose transport through enterocytes is energy- and time-dependent. Chlorpromazine, nystatin and EIPA all inhibited the endocytosis of NK to varying degrees, indicating that t...
Source: Xenobiotica - November 16, 2023 Category: Research Authors: Huawei Feng Chang Liu Qingqing Liu Jie Wang Yingyue Zeng Yue Sun Man Zhang Hui Zhang Zhikui Liu Jian Zhao Hongsheng Liu Source Type: research
Predicting routes of phase I and II metabolism based on quantum mechanics and machine learning
In this study, we describe the development and validation of a 'WhichEnzyme' model that accurately predicts the enzyme families most likely to be responsible for a drug-like molecule's metabolism. Furthermore, we combine this model with our previously published regioselectivity models for Cytochromes P450, Aldehyde Oxidases, Flavin-containing Monooxygenases, UDP-glucuronosyltransferases and Sulfotransferases - the most important Phase I and Phase II drug metabolising enzymes - and a 'WhichP450' model that predicts the Cytochrome P450 isoform(s) responsible for a compound's metabolism. The regioselectivity models are based ...
Source: Xenobiotica - November 15, 2023 Category: Research Authors: Mario Öeren Peter A Hunt Charlotte E Wharrick Hamed Tabatabaei Ghomi Matthew D Segall Source Type: research
Pharmacokinetic evaluation of oxaliplatin combined with S-1 (SOX) chemotherapy in a rat model of colorectal cancer with acute kidney injury: Predictive renal biomarkers for dose optimization
This study investigated the pharmacokinetics of SOX chemotherapy and renal biomarkers in rats.AKI was prepared by renal ischemia-reperfusion injury in 1,2-dimethylhydrazine-induced colorectal cancer model rats. Serum creatinine (sCr) levels were determined as a renal biomarker. After administration of S-1 (2 mg/kg tegafur) and oxaliplatin (5 mg/kg), drug concentrations of tegafur, 5-FU, and platinum were measured in the plasma and tumors.No alterations in the area under the plasma concentration-time curve (AUC0-24h ) values of 5-fluorouracil were observed between control and AKI model rats. The tumor concentrations of 5-fl...
Source: Xenobiotica - November 15, 2023 Category: Research Authors: Takumi Tanaka Shinji Kobuchi Yukako Ito Toshiyuki Sakaeda Source Type: research
Predicting routes of phase I and II metabolism based on quantum mechanics and machine learning
In this study, we describe the development and validation of a 'WhichEnzyme' model that accurately predicts the enzyme families most likely to be responsible for a drug-like molecule's metabolism. Furthermore, we combine this model with our previously published regioselectivity models for Cytochromes P450, Aldehyde Oxidases, Flavin-containing Monooxygenases, UDP-glucuronosyltransferases and Sulfotransferases - the most important Phase I and Phase II drug metabolising enzymes - and a 'WhichP450' model that predicts the Cytochrome P450 isoform(s) responsible for a compound's metabolism. The regioselectivity models are based ...
Source: Xenobiotica - November 15, 2023 Category: Research Authors: Mario Öeren Peter A Hunt Charlotte E Wharrick Hamed Tabatabaei Ghomi Matthew D Segall Source Type: research
Pharmacokinetic evaluation of oxaliplatin combined with S-1 (SOX) chemotherapy in a rat model of colorectal cancer with acute kidney injury: Predictive renal biomarkers for dose optimization
This study investigated the pharmacokinetics of SOX chemotherapy and renal biomarkers in rats.AKI was prepared by renal ischemia-reperfusion injury in 1,2-dimethylhydrazine-induced colorectal cancer model rats. Serum creatinine (sCr) levels were determined as a renal biomarker. After administration of S-1 (2 mg/kg tegafur) and oxaliplatin (5 mg/kg), drug concentrations of tegafur, 5-FU, and platinum were measured in the plasma and tumors.No alterations in the area under the plasma concentration-time curve (AUC0-24h ) values of 5-fluorouracil were observed between control and AKI model rats. The tumor concentrations of 5-fl...
Source: Xenobiotica - November 15, 2023 Category: Research Authors: Takumi Tanaka Shinji Kobuchi Yukako Ito Toshiyuki Sakaeda Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css-MRTpo method and chimeric mice with humanised livers
Xenobiotica. 2023 Nov 8:1-26. doi: 10.1080/00498254.2023.2280785. Online ahead of print.ABSTRACTPredicting plasma concentration-time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css-MRTpo, an empirical method, using chimeric mice with humanised livers capable of generating human-disproportionate metabolites.Azilsartan and AZ-M2 were administered to humanised chimeric mice, and pharmacokinetic parameters were obtained. Pharmacokinetic data for DS-1971a and DS-M1 in humanised chimeric mice were obtained from the literature. T...
Source: Xenobiotica - November 8, 2023 Category: Research Authors: Hidetaka Kamimura Shotaro Uehara Nao Yoneda Hiroshi Suemizu Source Type: research
Tree shrew cytochrome P450 2E1 is a functional enzyme that metabolises chlorzoxazone and < em > p < /em > -nitrophenol
In this study, a novel CYP2E1 was isolated from tree shrew liver and was characterised in comparison with human, dog, and pig CYP2E1. Tree shrew CYP2E1 and human CYP2E1 showed high amino acid sequence identity (83%) and were closely related in a phylogenetic tree.Gene and genome structures of CYP2E1 were generally similar in humans, dogs, pigs, and tree shrews. Tissue expression patterns showed that tree shrew CYP2E1 mRNA was predominantly expressed in liver, just as for dog and pig CYP2E1 mRNAs. In tree shrews, recombinant CYP2E1 protein and liver microsomes metabolised chlorzoxazone and p-nitrophenol, probe substrates of...
Source: Xenobiotica - November 7, 2023 Category: Research Authors: Genki Ushirozako Norie Murayama Kyoko Tsukiyama-Kohara Hiroshi Yamazaki Yasuhiro Uno Source Type: research
Tree shrew cytochrome P450 2E1 is a functional enzyme that metabolises chlorzoxazone and < em > p < /em > -nitrophenol
In this study, a novel CYP2E1 was isolated from tree shrew liver and was characterised in comparison with human, dog, and pig CYP2E1. Tree shrew CYP2E1 and human CYP2E1 showed high amino acid sequence identity (83%) and were closely related in a phylogenetic tree.Gene and genome structures of CYP2E1 were generally similar in humans, dogs, pigs, and tree shrews. Tissue expression patterns showed that tree shrew CYP2E1 mRNA was predominantly expressed in liver, just as for dog and pig CYP2E1 mRNAs. In tree shrews, recombinant CYP2E1 protein and liver microsomes metabolised chlorzoxazone and p-nitrophenol, probe substrates of...
Source: Xenobiotica - November 7, 2023 Category: Research Authors: Genki Ushirozako Norie Murayama Kyoko Tsukiyama-Kohara Hiroshi Yamazaki Yasuhiro Uno Source Type: research
< em > N, N < /em > -dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an < em > in vitro < /em > investigation
Xenobiotica. 2023 Nov 2:1-8. doi: 10.1080/00498254.2023.2278488. Online ahead of print.ABSTRACTN, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT.This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high-...
Source: Xenobiotica - November 2, 2023 Category: Research Authors: Emma Eckern äs Alicia Macan-Sch önleben Moa Andresen-Bergstr öm Sofia Birgersson Kurt-J ürgen Hoffmann Michael Ashton Source Type: research
< em > N, N < /em > -dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an < em > in vitro < /em > investigation
Xenobiotica. 2023 Nov 2:1-10. doi: 10.1080/00498254.2023.2278488. Online ahead of print.ABSTRACTN, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the metabolic pathways are poorly understood. Increasing this understanding is an essential aspect of ensuring safe and efficacious use of DMT.This work aimed to investigate the cytochrome 450 (CYP) mediated metabolism of DMT by incubating DMT with recombinant human CYP enzymes and human liver microsomes (HLM) followed by analysis using high...
Source: Xenobiotica - November 2, 2023 Category: Research Authors: Emma Eckern äs Alicia Macan-Sch önleben Moa Andresen-Bergstr öm Sofia Birgersson Kurt-J ürgen Hoffmann Michael Ashton Source Type: research
