S.C. Fang

Interaction of selenium and mercury in the rat

Abstract Adult female rats were given orally a toxic (40 μmole/kg) or non-toxic (13 μmole/kg) dose of 203HgCl2 or 75Se-sodium selenite alone, 203HgCl2 plus various amounts of 75Se-selenite, non-labeled sodium selenate, seleno-methionine or seleno-cystine and 75Se-selenite plus non-labeled phenylmercuric acetate (PMA), or methylmercuric chloride (MMC). Tissue accumulation, subcellular incorporation and soluble protein binding of 203Hg and 75Se in the liver and kidney were studied. Treatment with sodium selenite modified the tissue distribution, subcellular binding and soluble protein binding of 203Hg in the rat. The 203Hg content of all tissues with the exception of kidney was higher in the selenite-treated rats, and the magnitude of increase was higher with higher dose up to a Se/Hg ratio = 1. In contrast, the 203Hg content of the kidney was decreased. Other selenium compounds also gave similar effect and the order of effectiveness is as follows: seleno-methionine > seleno-cystine > selenate > selenite. All four selenium compounds increased the incorporation of 203Hg into the crude nuclear and mitochondrial fractions and decreased that in the soluble fraction. Higher selenium dosages resulted in greater alterations. In the kidney the influence by sodium selenite on the incorporation of 203Hg was erratic and appeared to be dependent on the ratio of selenite and mercuric chloride dosages. 203Hg binding to liver-soluble proteins was altered by selenite and it was dosage-dependent. However, no significant change in 203Hg binding pattern of the kidney soluble protein was observed by simultaneously dosing with selenite. A reduction of 75Se-selenite in most tissues was caused by dosing with Hg2+, and the effect was dosage dependent. PMA and MMC gave different changes suggesting that their interactions with selenite were indeed complex. Neither mercury compound showed any effect on subcellular distribution of 75Se in both liver and kidney. However, high Hg2+ dosage abolished the two minor 75Se protein peaks in the liver and kidney soluble fractions.

The binding of various mercurial compounds to serum proteins

SummaryBinding study of Hg-labeled Hg2+, PMA, MMC and EMC to serum albumin of six mammalian species, bovine hemoglobin and bovine γglobulin is presented. Both MMC and EMC bound only weakly to serum albumin and γ-globulin and more strongly to hemoglobin; Hg2+ bound very strongly to both albumin and hemoglobin and weakly to γ-globulin; and PMA bound most strongly to albumin, next to hemoglobin and the least, to γ-globulin. The available binding sites varied from one to five per molecule of protein. Human serum albumin has the lowest association constants with all four mercurial compounds, indicating that it was not as tightly bound to mercurial compounds as found with serum albumins from other species.

The metabolism and distribution of 2,4,5-trichlorophenoxyacetic acid in female rats

Abstract [1- 14 C]-2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) was fed to pregnant and non-pregnant female rats at various dosages, and expired air, urine, feces, internal organs and tissues were analyzed for radioactivity. During the first 24 hr, 75 ± 7% of the radioactivity was excreted in the urine and 8.2 ± 4.6% in the feces. No 14 C was found in the expired air. There was no significant difference in the rate of elimination between the pregnant and nonpregnant rats, or among the dosages used. Radioactivity was detected in all tissues, with the highest concentration being found in the kidney. The maximum concentration of radioactivity in all tissues was generally reached between 6 to 12 hr after po dosing and then started to decline rapidly. Radioactivity was also detected in the fetuses and in the milk. The average biological half-life of 2,4,5-T in the organs was 3.4 hr for the adult rats and 97 hr for the newborn.

Elimination, tissue accumulation, and cellular incorporation of mercury in rats receiving an oral dose of 203Hg-labeled phenylmercuric acetate and mercuric acetate☆

Abstract The distribution of 203 Hg-labeled mercuric acetate and phenylmercuric acetate in several vital organs was studied by tracer technique after a single oral administration. The highest concentrations of mercury were found in the kidneys; next, in that order, were the liver, the lung and the heart. The accumulations in other organs were comparatively small. The major route of the excretion of both mercurials was via the feces, and small amounts were excreted in the urine. The average total excretion in 1 week reached 98% and 80% of the administered doses for inorganic mercury salt and PMA, respectively. Greater portions of these excretions were found in the first three days. Subcellular distribution of 203 Hg in rat liver and kidneys following an oral administration of PMA and inorganic mercuric salt have been investigated. The percentage distribution of mercury varied slightly between the liver and the kidney and remained quite constant throughout a 72-hour post dosage period.

The in vivo binding of mercury to soluble proteins of the rat kidney

Abstract The kinetics of the mercury-binding profiles of soluble proteins from the kidneys of rats receiving po phenylmercuric acetate (PMA) or mercuric acetate (Hg2+) were investigated. PMA and Hg2+ treatment resulted in different 203Hg-binding patterns during the first 48 hr, especially in peak 1 and 2 proteins molecular weight > 100,000 and between 40,000 and 60,000, respectively), which gradually became similar at later times. A very large portion of 203Hg was bound to a soluble protein of 8000–13,000 molecular weight (peak 3). The major characteristic of this protein is its capacity to bind mercury. Two rates of removal of PMA were observed for all kidney soluble proteins. The fast rate has a half-time of 19–22 hr; that of the slow process is 12–44 days. Only one slow rate of removal was observed with Hg2+, and the half-times were 10, 12, and 124 days for peaks 1, 2, and 3, respectively. Rats receiving multiple doses of PMA or Hg2+ also showed similar 203Hg-labeling profiles in the kidney soluble proteins, and a slight change of OD260 pattern with an increase in peak 3.

Influence of dietary selenite on the binding characteristics of rat serum proteins to mercurial compounds.

The effect of dietary selenite on the binding characteristics of serum proteins was investigated with rats. In the control serum, the maximal binding of phenylmercuric acetate (PMA) and methylmercuric chloride (MMC) to rat serum protein was approx. 18 and 9 nmoles per mg protein, respectively. The binding of Hg2+ was biphasic and it did not reach a maximum at the concentrations used. Selenite treatment caused a reduction in binding capacity of serum proteins to Hg2+ and PMA, and an increase in the binding affinities. However, there were no such changes for the binding of MMC. Selenite protection from mercury toxicity, therefore, acts not only via a change in tissue distribution and a change in the formation of seleno-proteins but, also, via a change in the binding characteristics to some mercury compounds. In the case of methylmercury, a different mechanism of protection must exist as the modification of tissue distribution, its binding to subcellular and soluble proteins and the binding characteristics remained equivocal.

Effect of DDT on photosynthesis of Selanastrum capricormutum

Abstract The effect of DDT (2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane) on carbon assimilation of a green alga, Selanastrum capricormutum was studied. DDT at concentrations between 3.6 and 36 ppb was inhibitory to the photosynthetic CO2 fixation (ethanol-soluble and/or ethanol-insoluble) and the longer the exposure to DDT, the greater the inhibition. Kinetic studies of photosynthetic CO2 fixation indicated that DDT stimulated the incorporation of carbon-14 into glycolic acid, a major compound of photorespiration and caused the concomittant suppression of flow of carbon-14 into aspartic acid, a major component of the C4-dicarboxylic acid pathway. The shift from an efficient pathway into a nonefficient pathway by DDT was interpreted to be through interruption of cyclic photophosphorylation.

A comparative study of the subcellular binding of phenylmercuric acetate and mercuric acetate in rat liver and kidney slices

Abstract Studies were made to determine the extent of uptake and the rate of binding of 203Hg-labeled phenylmercuric acetate (PMA) and mercuric acetate (Hg++) in rat kidney and liver slices at 37° and their distribution in subcellular fractions, after incubation in Krebs-Ringer phosphate solutions containing 10−4 M mercurials. The time course of uptake showed that the rat kidney slices rapidly took up both PMA and mercuric ion at the same rate while liver slices incorporated the two mercurials at a much slower rate, with PMA at about twice the rate of mercuric ion. In the study of mercury distribution in subcellular fractions the percentages of PMA or Hg++ bound to mitochondrial and microsomal fractions were low and remained almost constant during a 3-hour experimental period. The bindings of 203Hg from PMA or Hg++ into the nuclear fraction were high and tended to increase as the time of incubation increased, while the 203Hg in the soluble fraction was decreased with the time of incubation. When a comparison was made on the specific binding of mercurials, it revealed that the binding of PMA into mitochondrial, microsomal, and soluble fractions was generally 1.5 to 2 times greater than those of mercuric ion. Only in the nuclear fraction of kidney a greater binding of mercuric ion was noted. This difference in intracellular distribution may be responsible for the different toxicity of PMA and mercuric ion in biological systems.

Metabolic studies of 14C-labeled propham and chlorpropham in the female rat☆

Abstract The tissue distribution and excretion of 14C-labeled propham and chlorpropham were investigated in the adult female rat after a single oral dosage. The average 3-day urinary excretions of radioactivity were 55.9%, 82.6%, 79.5%, and 85.4% of an oral dose of chain [14C] chlorpropham, ring [14C] chlorpropham, chain [14C] propham, and ring [14C] propham, respectively. With chain [14C] chlorpropham 35.4 ± 7.5% of the administered radioactivity appeared in the respired air, whereas only 5.0 ± 0.8% was found in CO2 from chain [14C] propham. There was no significant difference in the rate of excretion or the route of elimination among rats receiving different oral dosages, ranging from less than 4 mg/kg to 200 mg/kg. The radioactivity was distributed in all tissues with highest concentration found in the kidney. The average biological half-life of 14C from chlorpropham and propham in most organs was short, ranging between 3 and 8 hr; however, in brain, fat, and muscle, the half-life was about twice the value for other organs. Both compounds were metabolized by hydrolytic and oxidative mechanisms and the resulting metabolites were excreted either as free forms or as conjugates. Subcellular distribution of 14C in the rat liver and kidney after an oral administration of chlorpropham and propham was investigated. The percentage distribution of 14C in the particulate and soluble fractions was dependent on the elapsed time after dosing.

Comparative study of uptake and tissue distribution of methylmercury in female rats by inhalation and oral routes of administration

The release of mercury to the environment from coal-fired power plants, mining, and smelting operations is of special concern since these sources are currently uncontrolled and the use of coal is expected to increase significantly. Mercury which is released into the environment becomes available for methylation. Methylation rates in ecosystems are a function of the mercury burden, bacterial population, and other physicochemical conditions. Analysis of mercury forms in the air around Tampa Bay, Florida, revealed that about 21% of mercury in the atmosphere is of methylmercury types. No detailed data concerning the uptake and absorption of inhaled vapor of methyl mercury compounds are available. This paper reports a study on the uptake and tissue accumulation of /sup 203/Hg-methylmercuric chloride following oral and inhalation administration in female rats.