Gerald M. Holder

The Metabolism and Excretion of Curcumin (1,7-Bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the Rat

Curcumin labelled with deuterium and tritium was prepared. Oral and intraperitoneal doses of [3H]curcumin led to the faecal excretion of most of the radioactivity. 2. Intravenous and intraperitoneal doses of [3H]curcumin were well excreted in the bile of cannulated rats. 3. The major biliary metabolites were glucuronides of tetrahydrocurcumin and hexahydrocurcumin. A minor biliary metabolite was dihydroferulic acid together with traces of ferulic acid. Metabolites were identified using chemical ionization mass spectrometry.

Metabolism of benzo[A]pyrene III. An evaluation of the fluorescence assay

Summary Fluorescence spectra of the twelve isomeric phenols and phenolate anions of benzo[a]pyrene have been determined. The 3- and 9-isomers had the strongest fluorescence as phenols or phenolate anions. Many of the phenolate anions have insignificant fluorescence compared to the 3-hydroxybenzo[a]pyrene anion, whereas the phenols have more comparable fluorescence. Comparison of the fluorescence in acid (i.e., phenols) and alkali (i.e., phenolate anions) produced by the phenolic products obtained from benzo[a]pyrene after incubation with hepatic microsomes or with a reconstituted system established that a substantial percentage (35–50%) of the phenolic products formed are not detected by the standard fluorimetric assay in alkali.

Negative ion chemical ionization GC/MS-MS analysis of dialkylphosphate metabolites of organophosphate pesticides in urine of non-occupationally exposed subjects

Low level exposure to organophosphate (OP) pesticides can be determined by the measurement of dialkylphosphate (DAP) metabolites in urine. An analytical method is presented here which can measure the metabolites dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), dimethyl dithiophosphate (DMDTP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP) at low levels. This was achieved by lyophilization of the urine, derivatization with pentafluorobenzyl bromide (PFBBr) and quantification by negative ion chemical ionization GC/MS-MS. The detection limits for the metabolites were 0.5 microg L(-1) DMP, 0.1 microg L(-1) DEP, 0.1 microg L(-1) DMTP, 0.04 microg L(-1) DMDTP, 0.04 microg L(-1) DETP and 0.02 microg L(-1) DEDTP. The RSD for the analytical method was 4-14% for the six metabolites. The method was used to monitor a group of non-occupationally exposed individuals in Sydney, Australia. The metabolites DMP, DEP, DMTP, DMDTP, DETP and DEDTP occurred in 73, 77, 96, 48, 100 and 2% of the samples with median values of 13, 3, 12, <1, 1 and 1 microg L(-1) respectively. The method is simple to use, sensitive and suitable for routine analysis of non-occupational exposure levels. These detection limits are between one and two orders of magnitude lower than those previously reported in the literature.

Academic Literacy Skills and Progression Rates amongst Pharmacy Students.

Abstract This article addresses relationships between academic literacy skills and progress in a university degree program. Academic literacy skills of enrolling cohorts of pharmacy students were measured on four criteria. Correlations were calculated between these literacy measures; the time taken to reach graduation; the Tertiary Entrance Rank (TER); and each final first‐year course mark. Results indicate that almost half the enrolling students lacked adequate English language resources necessary for tertiary study. More interesting was the lack of significant correlation between each of these literacy skills and the TER. Logistic regression indicated that measures on three separate literacy criteria were better predictors of university success than the TER alone. When each of these three literacy measures was combined with the TER, prediction of the time taken to reach graduation was improved above using the TER alone. The outcome of this research indicates not only the importance of identifying and su...

Comparison of rat and guinea pig as sources of the S9 fraction in the salmonella/mammalian microsome mutagenicity test

A highly significant enhancement of mutagenicity occurs with 11 polycyclic aromatic hydrocarbons when 3-methylcholanthrene-induced guinea pig liver S9 is substituted for Aroclor-induced rat liver S9 in the Ames test. The use of MC-induced guinea pig liver S9 is particularly valuable for detecting the weak mutagenicity of benz[c]acridine, which is barely positive in a standard Ames assay. However, anthracene and phenanthrene, which are generally considered not to be carcinogens, remain non-mutagenic for strain TA100. This enhancement of mutagenicity does not correlate with arylhydrocarbon hydroxylase activities of the various liver preparations and does not apply to certain other non-PAH mutagens, including beta-naphthylamine, aflatoxin B1 and 4-dimethylaminoazobenzene.

The biliary metabolism of butylated hydroxytoluene (3, 5‐di‐t‐butyl‐4‐hydroxy‐toluene) and its derivatives in the rat

The biliary metabolism of 3, 5‐di‐t‐butyl‐4‐hydroxybenzyl alcohol (BHT‐CH2OH), 3, 5‐di‐t‐butyl‐4‐hydroxybenzaldehyde (BHT‐CHO) and 3, 5‐di‐t‐butyl‐4‐hydroxybenzoic acid (BHT‐COOH) after parenteral administration has been examined in the rat and compared to that of 3, 5‐di‐t‐butyl‐4‐hydroxytoluene. Quantitative excretion and chemical examination of bile showed that in the enterohepatic circulation BHT‐COOH or its ester glucuronide is the recirculating compound from the four compounds studied. Biliary excretion data are also presented for 1, 2‐bis(3, 5‐di‐t‐butyl‐4‐hydroxyphenyl)ethane.

Studies in the metabolism of carcinogenic polycyclic heteroaromatic compounds: I. The hepatic microsomal metabolism of 7-methylbenz[c]acridine

Abstract An enzyme assay for the metabolism of the carcinogenic aza-aromatic polycyclic compound 7-methylbenz[c]acridine has been developed using a modification of a radiochemical assay described for the polycyclic aromatic hydrocarbon benzo[a]pyrene by DePierre et al. [J. W. DePierre, M. S. Moron, K. A. M. Johannesen and L. Ernster, Analyt. Biochem. 63, 470 (1975)]and Van Cantfort et al. [J. Van Cantfort, J. DeGraeve and J. E. Gielen, Biochem. biophys. Res. Commun. 79, 505 (1977)]. When the activities of control microsomes and microsomes of phenobarbital-, 3-methylcholanthrene-and 7-methylbenz[c]acridine-pretreated animals were compared, strong similarities were displayed toward oxidation of benzo[a]pyrene and 7-methylbenz[c]acridine. These similarities were seen in turnover numbers, Michaelis constants, and inducibility of both enzyme systems. 7-Methylbenz[c]acridine afforded a type I difference spectrum with 3-methylcholanthrene-pretreated microsomes. It is suggested that 7-methylbenz[c]acridine is oxidized by the same or a similar set of enzymes which is responsible for benzo[a]pyrene metabolism.

The metabolism of butylated hydroxytoluene, (3, 5‐di‐t‐butyl‐4‐hydroxytoluene) in man

The urinary metabolites of [14C]-3,5-di-t-butyl-4-hydroxytoluene (BHT) in man have been estimated by Daniel, Gage & others (1967), who found that over 50% of a 40 mg oral dose is excreted in the urine during the 24 h after dosing. The major metabolite (present to the extent of 35% of the dose) was later identified as a glucuronide of 4-carboxy-2-( 1 -carboxy-I -methylethyl)-6-( 1 -formyl-1 -methylethyl)-

Rat liver microsomal metabolites of 7-methylbenz[c]acridine

The metabolism of the weak carcinogen 7-methylbenz[c]acridine (7MBAC) was examined in rat liver microsomes from 3-methylcholanthrene(MC)-induced animals by the use of mixed 14C- and 2H-labelled substrate. The three metabolites identified by spectroscopic and chromatographic examination were 7-OHMBAC and two dihydrodiols. The dihydrodiols were assigned structures consisted with attack on the 8,9- and 5,6- or K-region of the aromatic system.

Excretory and metabolic studies of isopropyl N-(3-chlorophenyl)carbamate in the rat.

Abstract The excretion and metabolic fate of [ 14 C]isopropyl N -(3-chlorophenyl)carbamate (alkyl[ 14 C]-CIPC) and isopropyl N -(3-chloro-[ 14 C]phenyl)carbamate (ring[ 14 C]-CIPC) was investigated in the rat after both intraperitoneal and oral dosage. The 4-day urinary excretion after administration of alkyl- and ring-labelled compounds was about 50 and 85% of the administered radioactivity, respectively, and with the alkyl-labelled compound 17–20% of the administered radioactivity appeared in the respired air. Studies with neomycin-treated rats indicated that hydrolysis of the carbamate link occurred systemically in the animal rather than in its intestine, and in vitro studies suggested that the site of hydrolysis might be the liver. The 6-hr biliary excretion of radioactivity accounted for 40% of an intravenous dose.