In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

2014 ◽  
Vol 281 (3) ◽  
pp. 276-284 ◽  
Author(s):  
Hitesh V. Motwani ◽  
Margareta Törnqvist
Keyword(s):  
Enzyme Kinetics ◽  
Hemoglobin Adducts ◽  
Species Extrapolation

scholarly journals Effective Compounds From Caesalpinia sappan L. on the Tyrosinase In Vitro and In Vivo

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2092005
Author(s):  
Yun Niu ◽  
Shengfeng Wang ◽  
Changqin Li ◽  
Jinmei Wang ◽  
Zhenhua Liu ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Enzyme Kinetics ◽  
Ethanol Extract ◽  
Skin Damage ◽  
Rat Serum ◽  
Caesalpinia Sappan ◽  
Competitive Inhibitors ◽  
Ethanol Extracts

Caesalpinia sappan L. has been used as an herbal medicine to treat skin damage as a facial cleanser. In this study, 8 known compounds (1-8), (3 R,4 S)-3-(3′,4′-hydroxybenzyl)-3,4-dihydro-2″,3″-dimethyl-3 H-[1,3]dioxolo [4,5-c]chromen-7-ol (1), brazilin (2), protosappanin A (3), protosappanin C (4), protosappanin B (5), caesalpin J (6), sappanone B (7), and sappanchalcone (8), were isolated from the 70% ethanol extract of C. sappan. The effects of 8 compounds and extracts of C. sappan on tyrosinase were assayed in vitro and in vivo. The results indicated that compounds 1, 2, 4, and 7 had activating effects on the tyrosinase. The experiments of enzyme kinetics showed that compounds 3 and 6 were competitive inhibitors on tyrosinase, while compound 6 was anticompetitive inhibitor. The 70% ethanol extract of C. sappan could reduce the contents of tyrosinase in rat serum, ie, the 70% ethanol extracts of C. sappan could inhibit the formation of melanin in vivo. Compounds 2, 3, 5, and 6 promoted the formation of tyrosinase in rat serum, while compound 7 inhibited the synthesis of tyrosinase in rat serum.

scholarly journals Testing Biochemistry Revisited: How In Vivo Metabolism Can Be Understood from In Vitro Enzyme Kinetics

2012 ◽  
Vol 8 (4) ◽  
pp. e1002483 ◽  
Author(s):  
Karen van Eunen ◽  
José A. L. Kiewiet ◽  
Hans V. Westerhoff ◽  
Barbara M. Bakker
Keyword(s):  
Enzyme Kinetics ◽  
In Vivo Metabolism

Do In Vitro Enzyme Kinetics Predict In Vivo Radiotracer Kinetics?

2001 ◽  
pp. 105-108
Author(s):  
Scott E. Snyder ◽  
Theodore Bryan ◽  
Neeraja Gunupudi ◽  
Elizabeth R. Butch ◽  
Michael R. Kilbourn
Keyword(s):  
Enzyme Kinetics

scholarly journals Model Selection in Toxicology: Principles and Practice

1990 ◽  
Vol 9 (3) ◽  
pp. 291-302 ◽  
Author(s):  
Shayne C. Gad
Keyword(s):  
Model Selection ◽  
Test Organism ◽  
Class Model ◽  
Basic Principles ◽  
Human Effects ◽  
Species Extrapolation ◽  
Accuracy Of Prediction ◽  
Selection Of

The key assumptions underlying modern toxicology are that (1) animals can serve as accurate predictive models of toxicity in humans, (2) that selection of an appropriate model to use is the key to accurate prediction in humans, and (3) that understanding the strengths and weaknesses of any particular model is essential to understanding the relevance of specific findings to humans. It must first be made clear, however, that the term model encompasses more than a test organism. Then the basic principles underlying these assumptions and the general limitations of models (both in vivo and in vitro) can be critically examined. The actual practice of model selection and why it deviates from the generally accepted principles are overviewed, along with the issue of errors induced by the “high-class model” problem. Historical results as to the accuracy of prediction of human effects are summarized. Finally, the reasons that models fail to predict effects in humans in some cases are examined, along with methods and problems in cross-species extrapolation and the issue of species peculiarities.

Gas Chromatographic and Mass Spectrometric Determination of Hemoglobin Adducts of 1,3-Dinitrobenzene and 1,3,5-Trinitrobenzene in Shrew Cryptotis Parva

1999 ◽  
Vol 18 (5) ◽  
pp. 317-325 ◽  
Author(s):  
Steven R. Myers ◽  
Maria T. Pinorini-Godly ◽  
Tirumuru V. Reddy ◽  
F. Bernard Daniel ◽  
Gunda Reddy
Keyword(s):  
Acid Hydrolysis ◽  
Surface Waters ◽  
Environmental Contaminants ◽  
Gas Chromatography Mass Spectrometry ◽  
Hemoglobin Adducts ◽  
Organic Solvent Extraction ◽  
Basic Hydrolysis

1,3-Dinitrobenzene (DNB) and 1,3,5-trinitrobenzene (TNB) are used primarily in explosive compositions and munitions and have been detected as environmental contaminants of surface waters as well as ground waters near production waste disposal sites. Hemoglobin (Hb) adducts have recently been proposed as biological markers of exposure assessment for various environmental compounds, including nitroaromatics. In the present study, we have investigated the formation of DNB and TNB hemoglobin adducts in vivo and in vitro in the blood of shrew (Cryptotis parva). DNB and TNB hemoglobin adducts were detected by gas chromatography/mass spectrometry (GC/MS) after either basic (0.1 N NaOH) or acid (2 N HCl) hydrolysis followed by organic solvent extraction and derivatization of the corresponding amines. The levels of DNB-Hb adducts detected after basic hydrolysis (238.7 & pm; 50.2 pg/mg Hb) are higher than the corresponding levels detected after acid hydrolysis (52.5 & pm; 16.2 pg/mg Hb). For the TNB-Hb the levels after acid hydrolysis (132.2 & pm; 37.8 pg/mg Hb) are higher than the levels detected after basic hydrolysis (44.7 & pm; 15.3 pg-mg Hb). These results demonstrate the effectiveness of the hemoglobin adduct model for monitoring exposure to nitroaromatics.

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