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D R Bourcier

Publications and source records attributed to D R Bourcier.

9 recordsLinked to original sources
PubMed1991

Effect of ascorbic acid esters on hepatic glutathione levels in mice treated with a hepatotoxic dose of acetaminophen.

Acetaminophen (APAP) with or without ascorbyl stearate (AS) or ascorbyl palmitate (AP) was administered by gavage to male Swiss-Webster mice at a dose of 600 mg/kg for each chemical. The biochemical markers of hepatotoxicity, serum transaminases (serum glutamate pyruvate transaminase [SGPT], serum glutamate oxaloacetic transaminase [SGOT]) and serum isocitrate dehydrogenase (SICD) activities were monitored after APAP and APAP + AP or AS dosing. There were significant reductions in serum transaminase and SICD activities in the APAP- + ascorbate ester-treated animals as compared to APAP-positive controls. Oral coadministration of APAP with AP or AS did not prevent the initial hepatic GSH depletion (15 min-4 hr postdosing). However, hepatic GSH content began to rise in the APAP + AS or AP-treated animals at 4 hr and reached control values within 12 hr postdosing. Urinary mercapturate conjugates were also significantly higher in the APAP + AP or AS-treated animals as compared to APAP alone when measured over a 60-min postdosing period. Plasma sulfobromophthalein (BSP) retention was approximately eight times higher in APAP-treated animals as compared to the APAP + ascorbate ester treatments indicating maintenance of hepatic excretory functions in presence of AP or AS. Prior depletion of hepatic GSH by diethyl maleate (DEM) did not alter hepatoprotective effects of AP or AS in the presence of APAP. Hepatic ascorbate levels also peaked at 4 hours after APAP + AP or AS treatments. The possible role of L-ascorbic acid esters in GSH regeneration following co-administration of a hepatotoxic dose and APAP is discussed.

Acetaminophen↗
PubMed1988

Influence of ascorbic acid esters on acetaminophen-induced hepatotoxicity in mice.

Groups of male Swiss-Webster mice were gavaged with acetaminophen (APAP), APAP + ascorbyl stearate (AS), or APAP + ascorbyl palmitate (AP) at a dose of 600 mg/kg for each chemical. APAP alone caused a significant increase in liver weight/body weight ratio and hepatic glutathione (GSH) depletion. Co-administration of the ascorbate esters AP or AS with APAP prevented an increase in liver weight/body weight ratios and hepatic glutathione depletion. APAP + AS treatments caused significantly greater reductions in rectal temperature at 15-30 min post-dosing periods when compared to APAP + AP or AS treatments. Blood levels of APAP had the same relationship. The study indicates a correlation between APAP blood levels and antipyretic effect of APAP + AS and APAP + AP coadministrations. While both ascorbate esters probably afford protection against APAP-induced hepatotoxicity in mice by reducing the reactive intermediate back to the parent compound, the APAP + AS combination provides better therapeutic efficacy as an antipyretic at the 15-30 min post-dosing periods.

Acetaminophen↗
PubMed1984

Tissue distribution and pharmacokinetics of 3H-butylated hydroxyanisole in female mice.

Butylated hydroxyanisole (BHA), a commonly used food additive, is a phenolic antioxidant. While metabolism of BHA has been studied in dog, man, rabbit and rat, information on tissue distribution is limited to rat and dog. Time dependent distribution and elimination of 3H-BHA following a single oral dose of 50 mg/kg body weight in female Swiss-Webster mice were investigated. Animals were sacrificed at time intervals up to 168 h after dosing. Levels of 3H were determined by liquid scintillation counting in the following tissues: brain, blood, serum, fat, heart, kidney, liver, lung, skeletal muscle and spleen. In most tissues the decline of BHA (log) was nonlinear with respect to time; a biphasic, post-absorptive aspect was observed. The highest 3H activity was noted in kidney and liver 15 min after dosing. The lowest activity was in fat. In addition, a peak 3H activity was recorded at 3 and 10 h after dosing for the blood and brain, respectively. Distribution of the 3H-BHA in mouse organs is similar to that in rat.

Animals↗
PubMed1984

Cellular distribution of inorganic mercury and its relation to cytotoxicity in bovine kidney cell cultures.

A bovine kidney cell culture system was used to assess what relationship mercuric chloride (HgCl2) uptake and subcellular distribution had to cytotoxicity. Twenty-four-hour incubations with 0.05-50 micro M HgCl2 elicited a concentration-related, with 1.0 nmol/10(6) cells at the IC50. Measurement of Hg uptake over the 24-h exposure period revealed a multiphasic process. Peak accumulation was attained by 1 h and was followed by extrusion and plateauing of intracellular Hg levels. Least-squares regression analysis of the cytotoxicity and cellular uptake data indicated a potential relationship between the Hg uptake and cytotoxicity (r = 0.91). However, the subcellular distribution of Hg was not concentration-related. Mitochondria and soluble protein fractions accounted for greater than 65% of the cell-associated Hg at all concentrations. The remaining Hg was distributed between the microsomal (6-10%) and nuclear and cell debris (11-22%) fractions at all concentrations tested. Less than 20% of the total cell-associated Hg was bound with metallothionein-like protein.

Animals↗
PubMed1983

Subcellular distribution of alpha-chaconine in mouse hepatocytes.

alpha-Chaconine is a toxic steroidal alkaloid present as a glycoside in potatoes. alpha-Chaconine was previously reported to bind with cell homogenates of various tissues. The extent of binding of 3H-alpha-chaconine in various macromolecular and subcellular fractions of liver after oral administration in female Swiss-Webster mice was investigated. No binding of this alkaloid was noted with isolated DNA or RNA fractions. The proportion of bound activity increased as the time between dosing and sampling increased, although the total alkaloid present in the organelles decreased. The extent of binding did not change when the doses ranged between 1 and 10 mg/kg. Induction of liver microsomal enzymes by treatment with dibenzo[a]pyrene increased the percent binding in all fractions except the proteins in the post-microsomal supernatant. Similar treatment with Aroclor 1254 and phenobarbital failed to produce increased binding in any of the fractions.

Animals↗
PubMed1982

Accumulation and depletion of cadmium and lead in tissues and milk of lactating cows fed small amounts of these metals.

Groups of lactating cows were fed 0, 40, and 200 mg of added cadmium (as chloride) and 0, 100, and 500 mg of added lead (as acetate) per animal per day in separate experiments. Milk and blood were sampled periodically and analyzed for concentrations of metal ions. Metal feeding was discontinued after 3 mo, and selected animals were necropsied for tissue residue studies. Remaining animals were continued on control ration for another 3 mo and then killed and tissues obtained. Cadmium feeding did not produce a dose-related increase of this metal in blood, milk, or skeletal muscle. Liver and kidneys were the primary organs of cadmium accumulation, and concentration of cadmium in these organs continued to rise during 3 mo of feeding the control diet after the initial exposure period. Lead did not accumulate in skeletal muscle but showed a dose-related increase in blood, milk, bone, liver, and kidney. In most tissues there was a rapid decline of lead concentrations after cessation of treatment, except in bone. Low dietary intake of cadmium and lead do not produce an appreciable rise of these metals in edible products, e.g., milk or meat. Of the tissues analyzed, liver and kidney accumulate both cadmium and lead, and cadmium especially persists in these organs for long periods. Bone is the primary site of deposition for lead but not cadmium.

Animals↗
PubMed1981

Effects of vanadium on immunologic functions.

Exposure of mice to vanadium caused a dose-related but nonsignificant decrease in the antibody-forming cells in the spleen of animals challenged with sheep erythrocytes. Delayed hypersensitivity reaction was not affected in similarly sensitized animals. Serum immunoglobulins were also not altered by the vanadium treatment. Splenic lymphocytes obtained at 1, 4, 8 and 13 wk of exposure to 0, 1, 10, and 50 mg of vanadium per liter of drinking water showed an increased DNA synthesis related to vanadium treatment when cultured in the presence of phytohemagglutinin and pokeweed mitogen but not with bacterial lipopolysaccharide. Addition of vanadium to splenic cultures in vitro caused a marked enhancement of lymphocyte transformation at low concentrations, whereas a decreased cellular proliferation was observed at high concentrations of vanadium.

Animals↗
PubMedDate not supplied

A stationary cold-vapor technique for the determination of submicrogram amounts of mercury in biological tissues by flameless atomic absorption spectrophotometry.

A procedure is provided for the determination of mercury in animal tissue using a single unit stationary cold-vapor generator utilizing atomic absorption spectrophotometry. The entire reduction-absorption cell is fitted to the burner mount on the instrument. Sample digests are introduced into the sample compartment along with reductant, and background corrected absorbance is measured after three minutes of sample-reductant mixing. The method is sensitive to 2 ng Hg (0.50 ng/mL Hg at 0.0044 absorbance units), which corresponds to 25 ng Hg per gram wet tissue using the prescribed digestion procedure. Reproducibility and accuracy are comparable to conventional cold-vapor techniques and the fact that relatively small sample aliquots (4.0 mL) are used for analysis provides for multideterminations of Hg in a single tissue digest; this is not ordinarily possible using conventional cold-vapor methods. A total of 15 digested tissue sample can be analyzed per hour. The method is proposed as an alterative to presently used cold-vapor Hg techniques.

Animals↗