In vitro and in vivo metabolic activation of berbamine to quinone methide intermediate

2016 ◽  
Vol 31 (4) ◽  
pp. e21876 ◽  
Author(s):  
Yao Sun ◽  
Tong Yao ◽  
Hui Li ◽  
Ying Peng ◽  
Jiang Zheng
Keyword(s):  
Metabolic Activation ◽  
Quinone Methide

Identification of Quinone Methide Intermediate Resulting from Metabolic Activation of Icaritin in Vitro and in Vivo

2019 ◽  
Vol 32 (6) ◽  
pp. 969-973
Author(s):  
Yan Chen ◽  
Xiucai Guo ◽  
Yufei Ma ◽  
Xingjia Hu ◽  
Ying Peng ◽  
...  
Keyword(s):  
Metabolic Activation ◽  
Quinone Methide

scholarly journals In vitro versus in vivo metabolic activation of mutagens.

1973 ◽  
Vol 6 ◽  
pp. 71-82 ◽  
Author(s):  
H V Malling ◽  
C N Frantz
Keyword(s):  
Metabolic Activation

scholarly journals Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianan Zhang ◽  
Morgan E. Walker ◽  
Katherine Z. Sanidad ◽  
Hongna Zhang ◽  
Yanshan Liang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Metabolic Activation ◽  
Consumer Products ◽  
Environmental Chemicals ◽  
Intestinal Microbes ◽  
Targeted Inhibition

AbstractEmerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

Studies on the dehydrogenative polymerization of monolignol β-glycosides. Part 6: Monitoring of horseradish peroxidase-catalyzed polymerization of monolignol glycosides by GPC-PDA

Holzforschung ◽  
2010 ◽  
Vol 64 (2) ◽  
Author(s):  
Yuki Tobimatsu ◽  
Toshiyuki Takano ◽  
Hiroshi Kamitakahara ◽  
Fumiaki Nakatsubo
Keyword(s):  
Horseradish Peroxidase ◽  
Reaction System ◽  
Water Soluble ◽  
Quinone Methide ◽  
Efficient Production ◽  
Hydroxyl Groups ◽  
Photodiode Array Detection ◽  
Dehydrogenative Polymerization

Abstract Horseradish peroxidase (HRP)-catalyzed dehydrogenative polymerization of guaiacyl (G) and syringyl (S)-type monolignol γ-O-glucosides, isoconiferin (iso-G) and isosyringin (iso-S), which contain a hydrophilic glucosyl unit on γ-position of coniferyl alcohol and sinapyl alcohol, respectively, was monitored by gel permeation chromatography coupled with photodiode array detection (GPC-PDA). Contrary to the conventional dehydrogenative polymerization of monolignols, the polymerization of the glycosides produces water-soluble synthetic lignins (DHPs) in a homogeneous aqueous phase. Taking advantage of this unique reaction system, the method was developed to follow the changes of molecular weights in the course of DHP formations. Moreover, PDA detection permits determination of oligomeric S-type quinone methide intermediates (QMs) formed as stable transient compounds during polymerization of iso-S. A detailed comparison of the polymerization profiles revealed entirely different behaviors of G- and S-type monomers. The data strongly support the view that the low reactivity of oligomeric S-type QMs impedes the formation of DHPs from S-type monomers. In copolymerization of G- and S-type monomers, it is conceivable that G-type phenolic hydroxyl groups serve as good nucleophilic reactants to scavenge S-type QMs resulting in efficient production of DHPs. As a consequence, the present approach can be a powerful tool to study the in vitro dehydrogenative polymerization providing further mechanistic insights into lignin polymerization in vivo.

Triazene metabolism. III. In vitro cytotoxicity towards M21 cells and in vivo antitumour activity of the proposed metabolites of the antitumour 1-aryl-3,3-dimethyltriazenes

1984 ◽  
Vol 62 (4) ◽  
pp. 396-402 ◽  
Author(s):  
Douglas J. Kohlsmith ◽  
Keith Vaughan ◽  
Stephen J. Luner
Keyword(s):  
Cell Line ◽  
Chemical Stability ◽  
Active Metabolite ◽  
Melanoma Cell Line ◽  
Antitumour Activity ◽  
Metabolic Activation ◽  
In Vitro Cytotoxicity ◽  
Structural Analogues

In vitro cytotoxicity of a series of antitumour triazenes towards the M21 melanoma cell line has been studied. Dimethyltriazenes are structural analogues of 5-(3,3-dimethyl-1-triazeno-)imidazole-4-carboxamide (Dacarbazine) and are inactive, which is consistent with the requirement for metabolic activation. Monomethyltriazenes and hydroxymethyltriazenes, the proposed metabolites of the dimethyltriazenes, are cytotoxic to the M21 cell line. A new series of 4-hydroxy-1,2,3-benzotriazines has been tested for in vitro cytotoxicity. A series of monoalkyltriazenes (Ar∙N=N∙NHR) has been tested for antitumour activity against the P388 lymphoma in vivo. Only monomethyltriazenes had significant antitumour activity, which supports the hypothesis that the monomethyltriazene is the active metabolite of the antitumour dimethyltriazenes. The activity of monomethyltriazenes in vivo is correlated with the chemical stability and t1/2 measurements in pH 7.5 phosphate buffer.

Genotoxicity Assessment of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

2005 ◽  
Vol 24 (6) ◽  
pp. 427-434 ◽  
Author(s):  
Gunda Reddy ◽  
Gregory L. Erexson ◽  
Maria A. Cifone ◽  
Michael A. Major ◽  
Glenn J. Leach
Keyword(s):  
Bone Marrow ◽  
World War Ii ◽  
Environmental Protection Agency ◽  
Bone Marrow Cells ◽  
Metabolic Activation ◽  
Maximum Tolerated Dose ◽  
Mouse Bone Marrow ◽  
Mouse Lymphoma

Hexahydro-1,3,5-trinitro-1,3,5-triazine, a polynitramine compound, commonly known as RDX, has been used as an explosive in military munitions formulations since World War II. There is considerable data available regarding the toxicity and carcinogenicity of RDX. It has been classified as a possible carcinogen (U.S. Environmental Protection Agency, Integrated Risk Information System, 2005, www.epa.gov/IRIS/subst/0313.htm ). In order to better understand its gentoxic potential, the authors conducted the in vitro mouse lymphoma forward mutation and the in vivo mouse bone marrow micronucleus assays. Pure RDX (99.99%) at concentrations ranging from 3.93 to 500 μg/ml showed no cytotoxicity and no mutagenicity in forward mutations at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells, with and without metabolic activation. This finding was also confirmed by repeat assays under identical conditions. In addition, RDX did not induce micronuclei in mouse bone marrow cells when tested to the maximum tolerated dose of 250 mg/kg in male mice. These results show that RDX was not mutagenic in these in vitro and in vivo mammalian systems.

scholarly journals Stimulation of neutrophil oxidative metabolism by the alternate pathway of complement activation: a mechanism for the spontaneous NBT test

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 843-849 ◽  
Author(s):  
RG Strauss ◽  
AM Mauer ◽  
T Asbrock ◽  
RE Spitzer ◽  
AE Stitzel
Keyword(s):  
Complement Activation ◽  
Oxidative Metabolism ◽  
Alternative Pathway ◽  
Metabolic Activation ◽  
Biologically Active ◽  
Nitroblue Tetrazolium ◽  
Human Neutrophils ◽  
Alternate Pathway

Abstract The reduction of nitroblue tetrazolium dye by human neutrophils was measured in the presence of serum in which the complement system had been activated through the alternate pathway by interaction with inulin. Neutrophils incubated with serum inulin supernatants reduced the dye and showed a general increase in oxidative metabolism. The oxidation of glucose-1–14-C by supernatant prepared from selectively depleted sera indicated that the neutrophil-stimulating factor(s) was generated through the alternate pathway of complement activation. The possibility that inulun had been ingested as a particle was ruled out by light microscopy and radiolabeling studies. The failure of neutrophils stimulated by the serum-inulun supernatants to migrate after exposure to a chemotactic agent suggested that the site of neutrophil-complement interaction was on the cell membrane. It is concluded from these results that biologically active fragments generated through the alternative pathway of complement activation can stimulate neutrophil metabolism in the absence of phagocytosis. Interaction of such fragments with circulating neutrophils in vivo and the subsequent metabolic activation of these cells is one explanation for the spontaneous reduction of nitroblue tetrazolium dye in vitro by neutrophils from patients with certain infections and inflammatory disorders.

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