In vivo incorporation of [14C]leucine into brain protein of mice treated with methylmercury and thiol complexes of methylmercury.

The effect of methylmercury and thiol complexes of methylmercury on inhibition of protein synthesis was evaluated. Mice were injected (i.p.) with the following treatments: methylmercuric chloride, methylmercury-glutathione, methylmercury-cysteinylglycine and control (vehicle) for 10 days. Ten animals from each group were injected with [14C]leucine 90 min prior to death. The brains were removed and the extracted protein was subjected to liquid scintillation analysis. Mice receiving the methylmercury and methylmercury-glutathione treatments exhibited significantly greater weight loss than the control while the methylmercury-cysteinylglycine treatment was not significantly different than the control. Incorporation of [14C]leucine into brain protein was significantly depressed in the methylmercury (81% of control) and the methylmercury-glutathione (79% of control) treatments. Protein synthesis in mice receiving the methylmercury-cysteinylglycine complex although not significantly different than the methylmercury treatments was only 92% of the control mice.

Effect of ingested benzo[a]pyrene and cadmium on tissue accumulation, hydroxylase activity, and intestinal morphology of the black sea bass, Centropristis striata.

Black sea bass, Centropristis striata, were fed shrimp containing [14C]benzo[a]pyrene (200 ppb) in the presence and absence of cadmium (10 ppm) for 10 days. Concentrations of cadmium in muscle tissue were significantly higher when both cadmium and benzo[a]pyrene were ingested simultaneously by the fish. Results indicate that selected tissue concentrations of total benzo[a]pyrene compounds (parent and metabolites) were not affected by the presence of cadmium. The bile contained the majority of benzo[a]pyrene found for all treatments. Ingestion of both contaminants had no effect on hepatic benzo[a]pyrene hydroxylase activity. Histological evidence from the feeding study demonstrated the presence of subcellular inclusions in the intestinal columnar cells and the combined effects of both contaminants appeared greater than either alone.

The toxicity, distribution and elimination of methylmercury in mice following intracerebral injection.

Intracerebral injection of methylmercury (CH3Hg) into the mouse brain resulted in significant weight loss and the appearance of characteristic neurological disturbances associated with CH3Hg intoxication. Neurological effects appeared dependent upon a minimum injected dose of 16 micrograms of CH3Hg corresponding to a CH3Hg concentration in the brain of 32 micrograms/g. Methylmercury was rapidly eliminated from the brain resulting in 40% and 5% remaining in the brain at 10 min and 7 days, respectively. The half-lives of CH3Hg in the tissues/organs were relatively short, ranging from 1.6 days for the cerebellum to 9.9 days for the liver and intestine. At the 10 min interval following injection, 22% of the injected 203Hg was found in the red blood cells which declined to 3% at the end of 7 days. The kidney concentration of 203Hg rapidly increased to 8% of the injected dose at 4 hr and remained at 5% of the body CH3Hg burden after 8 hr. The rapid elimination of 203Hg from the brain following intracerebral injection indicates that the blood brain barrier does not play a significant role in the retention of CH3Hg.

Toxicity, distribution, and elimination of thiol complexes of methylmercury after intracerebral injection.

Intracerebral injection of CH3Hg and CH3Hg complexed with glutathione (GSH), cysteine (cys), cysteinylglycine (cys-gly), and homocysteine (homocys) resulted in differences in toxicity. Criteria based on neurological indices, mortality, and weight loss indicated that the cys-gly complex of CH3Hg was significantly less toxic than CH3Hg or the other complexes. The other complexes of CH3Hg (GSH, homocys, and cys) were also found to be less toxic than CH3Hg. The selenium status of the animal did not seem to significantly influence the toxicity of CH3Hg and the complexes. While CH3Hg complexed to cys-gly was significantly less toxic than CH3Hg alone, there were no differences observed in the CH3Hg half-life values or in the distribution of these compounds in the kidneys, brain, liver, and blood. It was observed, however, that the CH3Hg--cys-gly complex had higher fecal excretion on d 3 and 4 following intracerebral injection.

Methyl mercury and selenium interaction in relation to mouse kidney gamma-glutamyltranspeptidase, ultrastructure, and function.

The effects of methyl mercury (CH3Hg) and selenium (Se) on renal ultrastructure were investigated and correlated to changes in renal gamma-glutamyl transpeptidase (gamma-GTPase) activity, mercury (Hg) accumulation, and renal function (serum creatinine and urea nitrogen). Three experimental protocols were used to investigate CH3Hg and Se interactions of both Se-sufficient and Se-deficient mice involving ip injection of the following administered alone or in combination: CH3Hg (4.0 mg/kg) and Se (0.16 mg/kg) daily for 7 days, CH3Hg (1.0 mg/kg) and Se (0.08 mg/kg) daily for 20 days, and a single acute dose of CH3Hg (8.0 mg/kg). Acivicin (12 to 50 mg/kg), an antitumor glutamine antagonist, was also used as a highly effective specific inhibitor of the gamma-GTPase. Our results show that CH3Hg administered to Se-deficient mice for 7 or 20 days resulted in significant (p less than or equal to 0.05) but only moderate inhibition (20%) of gamma-GTPase activity and extensive renal ultrastructural damage. Acivicin-treated mice had significant inhibition of gamma-GTPase activity (80%) following a single injection while ultrastructural damage was substantial only after several days of administration. These results may indicate different modes of action of acivicin and CH3Hg. Acivicin inhibited gamma-GTPase prior to renal damage while CH3Hg produced greater pathological effects with only moderate gamma-GTPase inhibition. Renal damage from acute and chronic CH3Hg toxicity occurred after distinct neurological signs were present. Selenium administered to Se-deficient mice ameliorated both the neurotoxic effects and nephrotoxic action of CH3Hg. While Se and CH3Hg treatments caused some of the same ultrastructural pathology as the treatment with CH3Hg alone (cytoplasmic vacuolation, increased lysosomal profile, mitochondrial swelling, and extrusion of cellular masses into the tubular lumen), degeneration was not as extensive. Although the total doses administered during both the 7- and the 20-day studies were similar, mice from the chronic 20-day study showed greater ultrastructural pathological effects from CH3Hg. The primary effects of CH3Hg appeared to be on the lysosomal system, while acivicin exerted its effects on the mitochondrial and endoplasmic reticulum systems. The accumulation studies on Hg suggest that dietary Se may have only an initial protective effect against Hg accumulation in the kidney while injected Se offers longer protection.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of digestion in the black sea bass, Centropristis striata, on the chemical speciation of organically bound cadmium.

The process of digestion (in vivo and in vitro) upon the chemical form of intrinsic cadmium (Cd) in oysters was examined. Analyses of stomach contents of adult black sea bass (Centropristis striata), 6 hr after consuming oysters previously exposed to Cd, indicated that Cd was associated with five protein fractions having approximate molecular weights of greater than 160,000, 74,000, 38,000, 11,000 and less than 4000. After 24 hr of in vivo digestion, analyses of intestinal contents indicated that most of the detectable Cd was associated with smaller molecular weight compounds. Similar results were obtained in an in vitro digestion system; the Cd was associated with somewhat larger complexes than those found in the in vivo digestion. Free amino acids were present in the low-molecular weight organo-Cd fraction, suggesting a possible role of amino acids in intestinal Cd transport.