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Study of reactive metabolites of foo...

Buranachokpaisan, Thitiwan.

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Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity./
Author:	Buranachokpaisan, Thitiwan.
Description:	182 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: 2726.
Contained By:	Dissertation Abstracts International72-05B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3444910
ISBN:	9781124530840

Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity.
Buranachokpaisan, Thitiwan.

Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity. - 182 p.

Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: 2726.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2011.

Biologically reactive metabolites are known for their ability to bind to nucleophilic macromolecules (DNA, proteins, lipids) and their irreversible binding to hepatic proteins is known to lead to necrosis and liver damage. Dansyl glutathione (dGSH), a fluorescent surrogate of glutathione, was used to trap reactive metabolites formed during oxidative metabolism of food additives by rat liver microsomes. dGSH was not commercially available and had to be synthesized. Synthesis of dGSH was improved to achieve a higher yield by reaction in borate buffer. The method, using fluorescent-high performance liquid chromatography for detection/quantitation and mass spectrophotometer for identification, yielded dGSH adducts that are consistent with other studies. dGSH was also found to be a substrate of microsomal glutathione S-transferase enzymes.

ISBN: 9781124530840Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity.
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100 1 $a Buranachokpaisan, Thitiwan. $3 2100992
245 1 0 $a Study of reactive metabolites of food additives and contaminant (bisphenol-A) using dansyl glutathione, and the correlation with their hepatotoxicity.
300 $a 182 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-05, Section: B, page: 2726.
500 $a Adviser: Paul E. Thomas.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2011.
520 $a Biologically reactive metabolites are known for their ability to bind to nucleophilic macromolecules (DNA, proteins, lipids) and their irreversible binding to hepatic proteins is known to lead to necrosis and liver damage. Dansyl glutathione (dGSH), a fluorescent surrogate of glutathione, was used to trap reactive metabolites formed during oxidative metabolism of food additives by rat liver microsomes. dGSH was not commercially available and had to be synthesized. Synthesis of dGSH was improved to achieve a higher yield by reaction in borate buffer. The method, using fluorescent-high performance liquid chromatography for detection/quantitation and mass spectrophotometer for identification, yielded dGSH adducts that are consistent with other studies. dGSH was also found to be a substrate of microsomal glutathione S-transferase enzymes.
520 $a To correlate the extent of adduct formation with their toxicity, selected hepatotoxic food additives were studies at low (0.1 mM) and high (1 mM) concentrations and the rates of adduct formation (nmol/min/mg microsomal protein) were measured. Using the amount of dGSH adduct of acetaminophen formed under the same conditions as a reference, the adduct formation rates of anethole and pulegone correlated well with their toxicity profiles while those of eugenol and nordihydroguaiaretic acid did not. Examination of their structures suggested different roles that phase II conjugation could play: either as detoxification, in concurrent, hence, competing with phase I oxidation, or as facilitating excretion, during the metabolism depending on the functional group a compound possesses. Studies of reactive metabolites of a compound capable of undergoing such concurrent phase II conjugation in a system without phase II capability could result in a false positive. It is concluded that the extent of dGSH adduct, representing that of reactive metabolites, formed by rat liver microsomes correlate well with hepatotoxicity profile of a compound.
520 $a The method was utilized to examine reactive metabolites of bisphenol A, a food contaminant. Four bisphenol A-related adducts were identified, characterized, including their formation kinetics, and quantitated. The extent of the 3 stable adducts was in the range of 1.5 to 11 nmol/min/mg protein. This high adduct level, however, requires additional studies to further examine the potential toxicity of bisphenol A reactive metabolites.
590 $a School code: 0190.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Health Sciences, Toxicology. $3 1017752
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0572
690 $a 0383
690 $a 0487
710 2 $a Rutgers The State University of New Jersey - New Brunswick. $b Graduate School - New Brunswick. $3 1019196
773 0 $t Dissertation Abstracts International $g 72-05B.
790 $a 0190
791 $a Ph.D.
792 $a 2011
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3444910