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Biomedical subjects

J Brodeur

Publications and source records attributed to J Brodeur.

At least 73 records · Page 4Linked to original sources
PubMed1981

Plasma disappearance and biliary excretion of bromosulfophthalein in styrene-treated and styrene oxide-treated rats.

Treatment with a single ip dose of styrene (908 mg/kg) 5 h before iv injection of bromosulfophthalein (BSP) (50 mg/kg) in rats resulted in (1) a decrease (approximately 30%) in biliary flow during 10-25 min but an increase in such flow during 60-90 min after the BSP dose, (2) a delay in cumulative excretion (approximately 50%) of BSP in bile during 5-60 min (but the latter became close to the control value after 75 min, and (3) no change in plasma disappearance of BSP. The first two effects seemed to depend on the dose of styrene. After pretreatment (2 h) with styrene oxide (375 mg/kg ip), a greater diminution of bile flow (approximately 50%) and of cumulative excretion of BSP was observed during the entire 5-90 min of bile collection after BSP administration, but the plasma disappearance of BSP remained unaffected. These results suggest that intrahepatic metabolism (and not hepatic uptake) of BSP and/or its transport from liver to bile are impaired after styrene- or styrene oxide-induced liver injury.

Animals↗
PubMed1980

Influence of free fatty acid anion on the binding of warfarin to cytoplasmic proteins from rat liver.

In vitro binding studies have shown that warfarin binds strongly to both ligandins (Y) and Z protein obtained from rat liver cytosol with dissociation constants of 11.7 and 10.1 microM respectively. Increasing concentrations of oleate ion significantly increased the dissociation constant of warfarin with either protein, whereas laurate ion showed the same behavior only with Z protein. On the other hand, the binding of warfarin to liver cytoplasmic proteins in vivo was decreased in 72-h-pre-fasted rats, although such fasting failed to produce any increase in the in vivo levels of the cytoplasmic free fatty acids (FFA). However, based on the results of the in vitro binding study, it is suggested that changes in the composition of hepatic cytoplasmic free fatty acids as a result of fasting could reduce the in vivo binding of warfarin to Y and Z proteins and hence could lead to an increase of unbound warfarin in liver cytosol.

Animals↗
PubMed1980

Effects of fasting on the diuretic response and disposition of furosemide in rats.

The influence of fasting on the relationship between the disposition and diuretic effect of furosemide was studied in rats. Fasting consisted of withholding solid food, but not water, for a period of 16 h before administering furosemide (10 mg/kg, sc) or a saline vehicle. Normally fed animals also received furosemide or the vehicle. Fasting did not modify the diuretic or the natriuretic effect (per 100 g body weight) of furosemide. The distribution of total furosemide in plasma or tissues was not affected by fasting. On the other hand, fasting which produced increasing amounts of endogenous free fatty acids in plasma and kidneys increased the concentration of free furosemide in fasting plasma but not in fasting kidney or liver of rats. The in vitro binding constant of furosemide to physiological concentrations of plasma proteins was decreased from the control value by a factor of 6.5 as a result of fasting. Neither unchanged furosemide nor its metabolite in the urine was affected by fasting. Incubation of kidney cortex tissue slices with furosemide both in the presence and absence of free fatty acid indicated an inhibition of furosemide uptake in a manner closely parallel to inhibition by probenecid. Thus, failure to observe a more pronounced diuretic and saluretic effects of furosemide in fasted rats, in spite of higher concentration of free plasma furosemide, might be due to the inhibitory effect of endogenous free fatty acids and (or) other endogenous substances on the uptake of furosemide by renal tubular cells although some homeostatic control mechanisms related to fasting could also be involved.

Animals↗
PubMed1979

Effect of free fatty acid anion on the in vitro binding of 1-anilino-8-naphthalene sulfonate to cytoplasmic proteins from rat liver.

The influence of oleate ion, a free fatty acid anion, on the binding characteristics of 1-anilino-8-naphthalene sulfonate (ANS) with the cytoplasmic proteins (Y and Z) from rat liver has been examined using fluorescence spectroscopy. ANS binds strongly with both ligandin (Y) and Z protein at a single binding site with dissociation constants of 0.6 and 1.4 micron respectively. Increasing concentrations of oleate ion decreased the ANS binding with either protein by competing with the ANS binding site. Relative binding constant of oleate ion for the hepatic ligandin or Z protein was about 2 micron as determined from the competitive inhibition of ANS binding. These results suggest that variations in the hepatic cytoplasmic free fatty acid concentration may be important in regulating the capacity of Y and Z proteins to transport other organic anions.

Anilino Naphthalenesulfonates↗
PubMed1977

The influence of fasting on the disposition of warfarin in rats.

A study was undertaken to investigate the influence of fasting on the disposition of warfarin in rats. Fasting consisted of withholding solid food, but not water, immediately following warfarin (3 or 10 mg/kg s.c.) administration until sacrifice at different time intervals (3, 6, 12, 24 and 30 hours). Control animals were fed ad libitum. Total and unbound warfarin concentrations were measured in plasma and liver supernatant as well as unchanged warfarin and its metabolites in urine. The disposition of unbound warfarin was found to be markedly affected by fasting, especially at the 3 mg/kg dose: the disappearance rate of unbound warfarin from plasma was accelerated in fasted animals in contrast to that of total warfarin. In addition, unbound warfarin was cleared from plasma at a more rapid rate than total warfarin in both control and fasted animals. At the 10 mg/kg dose, the disposition of total and unbound warfarin was little affected by fasting. The concentration of unbound warfarin in the liver supernatant of fasted rats given warfarin, 3 mg/kg, was significantly increased at 6 and 24 hours of fasting. Plasma free fatty acids were significantly elevated starting at 6 hours, but no such difference was noticed with liver homogenate, except at 24 hours. The 24-hour urinary excretion of unchanged warfarin was higher in fasted rats, but fasting failed to produce any change in the excretion of warfarin metabolites. The results of the present investigation indicate that short periods of fasting influence the disposition of unbound warfarin without apparently modifying its biotransformation and further show the importance of plasma protein binding on the pharmacokinetics of warfarin.

Animals↗
PubMed1976

[Influence of various enzyme inductors and combinations of inductors on DDT residue elimination in rats].

A study was under-taken to investigate the influence of pretreatments with various hepatic microsomal enzyme inducers on the elimination of DDT residues in rats previously contaminated with p,p' -DDT at 5 mg/kg/day, during 20 days. The following inducers were used : phenobarbital (50 a mg/kg/day, i.p.), 3,4-benzopyrene (20 mg/kg/day, s.c.) and norethandrolone (20 mg/kg/day, s.c.), all given during 14 consecutive days. Each inducer was administered singly or in combination with the other two according to a 2 X 2 X 2 factorial experiment. The animals were then sacrificed for the measurement of p,p' -DDT, p,p' -DDD and p,p' -DDE residues in the blood, brain, abdominal fat, liver and kidneys. The results show that phenobarbital lowers markedly the concentration of total residues in the fat tissue and brain and that norethandrolone brings about a reduction of the residues in the blood, brain and kidneys, but not in the fat tissue. On the opposite, 3,4-benzopyrene produces an increase of the residues in the brain, liver and kidneys. Phenobarbital thus appears to be more efficacious than the other two inducers in facilitating the elimination of DDT residues from the fat tissue. In addition, it appears that under the experimental conditions used during this investigation, the elimination of DDT residues is not further accelerated by combining the inducers one with each other.

Abdomen↗
PubMed1976

The influence of fasting and stress on the response of rats to warfarin.

A study was undertaken to investigate the influence of fasting (24 hours), epinephrine (four 0.25 mg/kg s.c. doses at hourly intervals), adrenocorticotropin (two 40 I.U. s.c. doses at 2-hour intervals) and immobilization stress (4 hours) on the response of rats to some coumarin or indanedione anticoagulants. The anticoagulants were always administered first and were followed immediately or within the next hour by the appropriate challenge. Fasting produced a significant enhancement of the antiprothrombin response to warfarin (0.5 mg/kg i.v. or 0.75-3.0 mg/kg s.c.), bishydroxycoumarin (7.5 mg/kg i.p. or 10 mg/kg s.c.) and phenindione (40 mg/kg p.o). Epinephrine and immobilization stress, but not adrenocorticotropin, similarly prolonged the prothrombin time after warfarin (0.75-3.0 mg/kg s.c.). When used in the absence of anticoagulants, all challenges had no effect on the prothrombin time. In addition, fasting did not affect the response of anticoagulated animals to vitamin K. Plasma free fatty acids were significantly increased by the various challenges. The binding constant of warfarin to undiluted plasma proteins were decreased from the control value by a factor of 1.7 and 2.0 as a result of immobilization stress and fasting, respectively. Fasting per se increased the amount of bound endogenous free fatty acids per mole of protein; the latter parameter was further increased in the presence of warfarin. The present data show that fasting and stress enhance the anticoagulant response to warfarin and suggest that this might be due to an interference of endogenous free fatty acids with binding of warfarin to plasma proteins.

Adrenocorticotropic Hormone↗
PubMed1975

The effect of norethandrolone on organic ion transport by rat renal cortical slices.

Norethandrolone (NE) and other androgenic steroids have been shown to be renotropic in various species and have also been reported to have salutary effects in patients with diminished renal function. Renal cortical slices prepared from rats pretreated with NE showed an increased capability to concentrate p-aminohippuric acid (PAH). Pretreatment with NE failed to stimulate the transport of the organic base tetraethylammonium and the organic acid benzylpenicillin. Stimulation of PAH transport was observed after eight daily subcutaneous injections of NE. No stimulation was observed with shorter pretreatment intervals. When NE was given subcutaneously for 14 days at doses of 2.6 or 20 mg kg-1 day-1, significant stimulation of PAH transport was seen at all three dose levels but no dose-effect relationship was apparent. Stimulation of PAH transport was seen in female rats as well as castrated and intact males. In addition to its general anabolic properties, NE induces the synthesis of hepatic microsomal drug-metabolizing enzymes. For comparative purposes, therefore, the effect of pregnenolone-16 alpha-carbonitrile (PCN) was also investigated. This agent is a potent inducer of drug metabolism but is neither anabolic nor renotropic. When rats were pretreated with an inducing dose of PCN (75 mg kg-1 day-1 for 3 days), there was no significant stimulation of PAH transport. It would seem, then, that the stimulatory effect of NE on PAH transport is more closely associated with its generalized anabolic effect than with its ability to induce hepatic microsomal enzymes.

Aminohippuric Acids↗
PubMed1975

Fluorometric determination of delta-aminolaevulinate dehydratase activity in human erythrocytes as an index to lead exposure.

We describe a fluorometric method for determining delta-aminolaevulinate dehydratase (EC 4.2.1.24) activity in human erythrocytes and compare it with the existing colorimetric method. Incubation conditions are identical. In the proposed method, the porphobilinogen formed during incubation is converted to a stable and highly fluorescent uroporphyrin by heating for 20 min at 93 degrees C in an acidic medium in the presence of air. The correlation between results by the two methods was good (r = 0.89). We found a good negative correlation between the activity of the enzyme and the concentration of circulating lead with both methods (r = -0.61 for present method and -0.59 for colorimetric method) for groups of persons subjected to various degrees of lead exposure. Our method is more sensitive and accurate, requires less sample, and the fluorescence is more stable than is the color in the colorimetric method.

Colorimetry↗
PubMed1975

[The effect of pretreatment with enzyme inducers on the acute toxicity of DDT (1, 1-bis-(p-chlorophenyl)-2,2,2-trichloroethane) in rats].

A study was undertaken to investigate the influence of various hepatic enzyme inducers on the acute toxicity of the organohalogenated insecticide DDT. Adult female rats were pretreated with sodium phenobarbital (50 mg/kg/day during 5 days), 3-methylocholanthrene (20 mg/kg/day during 3 days), and norethandrolone (20 mg/kg/day during 14 days), and were then given 150 mk/kg of DDT per os. Phenobarbital was shown to lower the toxicity of DDT, norethandrolone had the opposite effect, and 3-methylcholanthrene was without any significant effect. After a phenobarbital pretreatment, the cerebral concentration of DDT was lowered, possibly as a result of an increased biotransformation of DDT to DDD in the liver. On the other hand, norethandrolone did not appear to modify the hepatic conversion of DDT to DDD, nor the cerebral concentration of DDT. Further studies are needed to explain the potentiating effect of norethandrolone on the acute toxicity of DDT.

Animals↗