Biomedical subjects

G W Lucier

Publications and source records attributed to G W Lucier.

At least 163 records · Page 9Linked to original sources

PubMed1975

Induction and suppression of hepatic and extrahepatic microsomal foreign-compound-metabolizing enzyme systems by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on a number of hepatic and extrahepatic foreign-compound-metabolizing enzyme systems in microsomes from rats, rabbits and guinea pigs were investigated. Following TCDD treatment, the N-demethylation of benzphetamine, aminopyrine and ethylmorphine was suppressed in hepatic microsomes from male but not from female rats. However, both cytochrome P-450 and benzpyrene hydroxylase were significantly stimulated in hepatic microsomes from both male and female rats at doses as small as 1 mug TCDD/kg body weight. The inductive effect on rat hepatic microsomal enzymes was considerably more persistent than the suppressive effect. Following a single oral dose of 25 mug TCDD/kg weight, benzpyrene hydroxylase of male rat liver microsomes remained significantly elevated for 73 days but the suppression of benzphetamine N-demethylase had gone after 35 days. The induction of benzpyrene hydroxylase in male rat liver microsomes by TCDD was independent of the age of the rat and the levels to which this enzyme was increased was similar in male rats of all ages. However, the suppression of benzphetamine N-demethylase in male rat liver microsomes was age related: the suppression was seen only in adult animals and in the very young (10 days old) the enzyme was actually induced by TCDD. Inductive effects appeared in both smooth and rough-surfaced hepatic microsomes from male rats but the suppression of N-demethylation occurred only in the smooth-surfaced microsomes (SER). In microsomes from extrahepatic tissues of the rat, induction of mixed-function oxidases (MFOs) by TCDD occurred only in the kidney. However, UDPglucuronyltransferase was induced in microsomes from lung, kidney, intestine and brain but not testes. The response in the rabbit and guinea pig to TCDD differed considerably from that in the rat. Benzpyrene hydroxylase was unaffected in hepatic microsomes from the guinea pig and actually suppressed in microsomes from rabbit liver. Benzphetamine N-demethylase was also suppressed in rabbit liver microsomes. Glucuronyl-transferase was unaffected by TCDD in microsomes from liver, lung or kidney of the rabbit and guinea pig. The only lung enzyme responsive to TCDD was biphenyl 4-hydroxylase of the rabbit and guinea pig. Suppression was not observed in any of the extraheptic tissues studied and may be confined to only certain hepatic systems.

Animals↗

PubMed1975

Methylmercury-cholinesterase interactions in rats.

The interaction of methylmercury hydroxide (MMH) and cholinesterases was studied in male and female rats. MMH administered subcutaneously in doses of 10 mg/kg for 2 days reduced the level of plasma cholinesterase (ButChE) by 68% in females and 47% in males while brain acetylcholinesterase (AChE) was unaffected. Normal females had higher but more variable ButChE levels than normal males. In a time-course experiment, a single dose of MMH (10 mg/kg) reduced ButChE levels when mercury levels reached 22 mug/ml in the blood. A 10% reduction in brain AChE was observed at 72 hours; however, mercury reached a concentration of only 2.0 mug/g in brain tissue. The determination of the Michaelis constant Km and maximum velocity value Vmax for butyrylcholine and ButChE in control and MMH-treated (1 mg/kg) animals indicated that MMH reduced Vmax only. Since no loss in ButChE activity occurred when MMH and control plasma were incubated in vitro, MMH is not a direct inhibitor of ButChE. Because only the inactive monomeric form of ButChE contains free sulfhydryl groups, it is postulated that MMH combines covalently with the sulfur, preventing formation of active enzyme. By analogy, it is believed this is also the case with AChE.

Animals↗

PubMed1975

Placental transfer of cadmium in rats: influence of dose and gestational age.

Placental transfer rates of cadmium were investigated in rats in relation to dose (0.1, 0.4, and 1.6 mg Cd/kg) and the gestational age (12, 15, and 20 days) when rats were treated. Pregnant rats were injected intravenously with a single dose of 109CdCl2 (approximately 20 muCi/animal), and animals were sacrificed after 24 hr. 109Cd concentrations were measured in the fetus, placenta, maternal liver, and blood. Cadmium crossed the placenta at all doses and at all gestational ages tested. However, higher percentages of administered cadmium accumulated in the fetus with increasing dose and increasing gestational age. For example, after pregnant rats were injected with low, middle, and high doses of Cd on day 12 of gestation, fetuses accumulated 0.0001, 0.0028, and 0.0095 per cent of the injected dose, respectively. Percentages of administered Cd detected in placental tissue did not change consistently with dose but Cd levels did increase with gestational age. Placental to maternal blood Cd concentration ratios increased with gestational age but not with dose. Maternal liver to fetal liver concentration ratios were 295, 137, and 27 for low, middle and high doses, respectively, 24 hr after pregnant rats were treated on day 20 of gestation. These results are discussed in relation to placental damage, metallothionein inducibility, and fetotoxicity.

Animals↗

PubMed1975

Phenobarbital protection against methyl mercury neophrotoxicity.

Phenobarbital injections to rats given a low oral dose level of methl mercury for 2 or 4 wk decreased methyl mercury-induced ultrastructural alterations in kidney proximal tubule cells, increased urinaryexcretion of inorganic mercury and increased blood concentrations of methylmercury. These effects were not seen after 2 wk of treatment but were highly significant after 4 wk.

Animals↗

PubMed1975

The effects of chronic oral methyl mercury exposure on the lysosome system of rat kidney. Morphometric and biochemical studies.

This report describes morphometric and biochemical changes in the renal lysosome system of rats exposed to 3, 5, or 10 p.p.m. concentrations of methyl mercury hydroxide in their drinking water for 4 weeks. Increased numbers of dense, granular lysosomes, previously found to contain mercury, were observed in tubule cells of rats receiving the 3 and 5 p.p.m. dose levels but not those of the 10 p.p.m. group. Tubule cells from animals given the 10 p.p;m. dose level displayed proteinaceous vacuoles with dense crystalloid structures, apical cytoplasmic extrusion, and cellular degeneration; Mitochondrial swelling within tubule cells of treated animals showed a marked dose-response relationship. Renal microsomal activity levels of ss-glucuronidase were strongly inhibited by methyl mercury hydroxide exposure at all dose levels, whereas the activity levels of acid phosphatase were unchanged. Lysosomal beta-glucuronidase was also inhibited by methyl mercury hydroxide exposure, whereas lysosomal acid phosphatase showed approximately a 2-fold increase in activity. The results are discussed in relation to the role of lysosomes in mediating the nephrotoxic effects of methyl mercury and other toxic trace metals.

Acid Phosphatase↗

PubMed1974