Absorption and disposition of 203Hg in the pregnant and nonpregnant hamster following oral administration of [203Hg]methylmercuric chloride

The absorption and disposition of ²⁰³Hg was determined in pregnant and nonpregnant golden hamsters by means of γ scintillation spectroscopy. The animals were given 5 μCi [²⁰³Hg]methylmercuric chloride orally on gestational Day 9. Urine and feces were collected until Day 15, when the animals were sacrificed. Adult and fetal tissues were analyzed for ²⁰³Hg concentrations. At 12 hr postintubation, pregnant hamsters absorbed more of the administered dose (96.10 ± 0.63% vs 92.02 ± 1.35%, : < 0.05) and eliminated less methylmercury in the feces (3.90 ± 0.63% vs 7.98 ± 1.35%, P < 0.05) than nonpregnant animals. Beyond 12 hr postintubation, the absorption and elimination patterns were similar in both groups. Comparison of organs from pregnant and nonpregnant animals revealed greater methylmercury concentrations in the cerebella, pons-medullas, and spleens of pregnant females. The fetal head was found to contain significantly more methylmercury than the fetal body (P < 0.001).     

Dose-Dependence of Methylmercury Metabolism

The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of ²⁰³MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1μg/gm. Above this level, the ratio of concentration in the brain and blood was increased.

The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in blood. The total Hg concentration in feces was always more than ten times that in urine.

Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain<5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of ²⁰³MeHg, the halftime for total Hg in blood was 49±2.8 days, and in the whole body 134±2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.     

Bio-availability and pharmacokinetics of cyproterone acetate-14C and ethinyloestradiol-3H after oral administration as a coated tablet (SH B 209 AB)

Eight young women were each given 2 mg cyproterone acetate-methyle-ne-¹⁴C and 50 μg ethinyloestradiol-6,7-³H, ingredients of the contraceptive SH B 209 AB, orally in coated tablet form. The ¹⁴C and ³H activity in plasma, urine and faeces was determined up to 7 or 10 days post-administration.Cyproterone acetate was absorbed completely. The maximum plasma level was reached between 30 minutes and 3 hours after administration. At this time 2.2 ± 0.6 % of the dose was found in total plasma, which corresponds to 24 ± 6 ng cyproterone acetate equivalents/ml. At first the plasma level decreased with a half-life of 7.9 ± 1.3 hr (distribution and elimination) and later with a half-life of 2.5±0.6 d (elimination).Elimination via urine was 37 ± 5%. Up to the 10th day after administration 91±2 % of the dose had been found in urine and faeces.Ethinyloestradiol was absorbed very rapidly and almost completely. The maximum plasma level was reached only 60 ± 30 minutes after administration. At this time 10 ± 2% of the dose could be found in the plasma, which corresponds to 2.1 ± 0.5 ng ethinyloestradiol equivalents/ml. Due to processes of distribution and elimination, the plasma level dropped up to about 8 hr post-administration with a half-life of 5.1±1.5 hr, later with a half-life of 27 ± 8 hr, corresponding to the rate of elimination. Ethinyloestradiol was eliminated in urine and faeces in the ratio 4: 6. 91 ± 9 % of the dose could be recovered in this investigation.     

Effect of rat's diet on 85Sr, 115mCd,and 203Hg absorption in suckling rats

Six-day-old suckling rats were artificially fed over 8 hr with cow's milk or rat's diet labeled with ⁸⁵Sr, ^115mCd, or ²⁰³Hg. The whole-body radioactivity was determined in a double-crystal scintillation counter every 24 hr over a 6-day period. Rat's diet caused a reduction in the whole-body retention of all radioisotopes which was highest for ²⁰³Hg and lowest for ⁸⁵Sr. All sucklings were killed 6 days after the radioisotope administration and the radioactivity was determined in the carcass and in the gut. Rat's diet reduced carcass retention by about 10% for ⁸⁵Sr, and two and three times for ^115mCd and ²⁰³Hg, respectively. Rat's diet also reduced gut retention by about 20% for ⁸⁵Sr, two times for ^115mCd and eight times for ²⁰³Hg. It is concluded that dietary factors are partly responsible for the high metal absorption in sucklings. This specially applies to mercury because rat's diet caused a considerable reduction in the whole-body retention of this metal primarily by decreasing its gut retention.     

Compartmental analysis for the evaluation of biological half-lives of cadmium and mercury in mouse organs

Repeated observations on the quantitative behavior of ¹⁰⁹Cd and ²⁰³Hg in various mouse organs after a single injection of these tracers revealed the fact that a clear difference of turnover characteristics exists between these nuclides, as was quantitatively determined by the compartmental analysis using electronic computer HITAC 5020. Loss patterns of ¹⁰⁹Cd in liver, kidney, and salivary gland fitted the two-compartment model. In each organ fast and slow biological half-lives were obtained from the two observed rate constants. Data from gastrointestinal tissues or contents conformed with the one-compartment model. Loss patterns of ²⁰³Hg in most mouse organs, except brain, fitted the one-compartment model with larger rate constants which were more than 10-fold those of ¹⁰⁹Cd. By comparing the parameters obtained in the fitted exponential functions for various organs, it was possible to define the interrelationship of the metabolic flow of the elements in the different organs. In cadmium, data from kidneys, livers, and salivary glands of subcutaneously injected animals were obtained which gave a common value for the parameter reflecting the pool size. Rate constants in kidneys and salivary glands were very small thus giving extremely long biological half-lives. Decay pattern of ¹⁰⁹Cd for the whole body was also examined in detail.     

Uptake,distribution, and metabolism of inhaled ethylmercuric chloride in the rat

The uptake and the tissue distribution of ethylmercuric chloride (EMC) by inhalation and oral administration were studied in adult female rats. The pulmonary uptake of EMC linearly increases with the time of exposure and is proportional to the concentration of EMC vapor. With the exception of stomach, intestine, and hair, the tissue distribution of²⁰³Hg from pulmonary uptake is quite similar to that from oral administration. The biological halflife of EMC in the organs is longer from pulmonary uptake than from oral administration. Kidney and liver convert EMC to in-organic mercury irrespective of the routes of administration. A small amount of²⁰³Hg is found in the fetus, and the fetal liver accumulates more²⁰³Hg than the fetal kidney.Technical Paper No. 3496, Oregon Agricultural Experiment Station, Corvallis, Oregon.     

Chemical Cyanosis-Anemia Syndrome

The oral intake of 2.6μCi of methyl-mercuric nitrate Hg 203 by three clinically healthy, white, male volunteers aged 37 to 44 years resulted in an accumulation in the liver and the head of the ²⁰³Hg. The main excretory route was the feces but the urinary excretion increased with time up to 30 days after the intake. The biological half-life was found with whole body measurements to be 70 to 74 days. The decline of ²⁰³Hg in the head was less rapid than in the rest of the body. No ²⁰³Hg was found in the sperm. A very rapid uptake was found in the erythrocytes. The main activity was localized in the liver (about 50% of the contents of the body) whereas the head contained about 10% of the total body content. After infinite time a weekly unit dose of methyl mercuric nitrate Hg 203 will result in a whole body burden of 15.2 units mercury.     

Urinary fluoride levels in Saudi individuals drinking tap and bottled water

The fluoride concentration in the urine samples of 130 Saudi individuals aged 16-70 years old living in Riyadh was determined using a fluoride-specific electrode (0.9262 ± 0.703 μ g ml^?1, 0.16-4.68 μ g ml^?1). There were differences in the urinary fluoride levels of the subjects. About 45.5% of the subjects had urinary fluoride less than 0.7 μ g ml^?1. Conversely, 22.3% of the screened subjects had urinary fluoride levels higher than 1.2 μ g ml^?1; this could increase the risk of dental and skeletal fluorosis. Since drinking water is considered to be the major source of fluoride, it was measured in 88 drinking water samples. Significant correlation between fluoride in urine and drinking water was found (r = 0.4341, p = 0.0237). Bottled water had significantly higher fluoride content (0.5205 ± 0.322 μ g ml^?1) than tap drinking water (0.1046 ± 0.0447 μ g ml^?1). About 67% of the screened water samples had low fluoride concentrations (< 0.3 μ g ml^?1) which is far below the recommended level for caries control.     

Bioactive lipids are altered in the kidney of chronic undernourished rats: is there any correlation with the progression of prevalent nephropathies?

Background

Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease.

Methods

Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination.

Results

Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca²⁺ homeostasis and the enzymes responsible for important lipid mediators such as phosphatidylinositol-4 kinase, sphingosine kinase, diacylglicerol kinase and phospholipase A₂. We observed a decrease in phosphatidylinositol(4)-phosphate (8.8?±?0.9 vs. 3.6?±?0.7 pmol.mg^?1.mim^?1), and an increase in phosphatidic acid (2.2?±?0.8 vs. 3.8?±?1.3 pmol.mg^?1.mim^?1), being these lipid mediators involved in the regulation of key renal functions. Ceramide levels are augmented in kidney tissue from RBD rats (18.7?±?1.4 vs. 21.7?±?1.5 fmol.mg^?1.min^?1) indicating an ongoing renal lesion.

Conclusion

Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.

     

Reduced cholesterol levels in renal membranes of undernourished rats may account for urinary Na+ loss

Purpose

It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats.

Methods

Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration.

Results

Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls.

Conclusion

Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.     

Food mineral composition and acid–base balance in rabbits

Summary Background Alkalirich diets are often recommended in human medicine to prevent the pathological consequences of nutritional acid load in conditions of impaired renal function. Aim of the study This study was undertaken in rabbits as common laboratory animals for basic medical research to explore the impact of high versus low dietary alkali intake on systemic acid–base balance and renal control in a typical herbivore. Methods Male rabbits (2.3–4.8 kg) were kept in a metabolism cage. The 24h urine and arterial blood samples were analysed for acidbase data. The metabolic CO₂ production was measured to calculate alveolar ventilation. Three randomized groups of animals were fed ad libitum with rabbit chow providing sufficient energy but variable alkali load, assessed by the ashes’ cationanion difference. Results The average daily nutritional alkali load (± SEM) was 67.1 ± 2.2 mEq · kg^–1 (N = 58) in the group on high, 45.4 ± 2.5 mEq · kg^–1 (N = 31) in the group on normal and 1.7 ± 0.5 mEq · kg^–1 (N = 11) in the group on low alkali food. Respective mean arterial base excess values (BE) were 1.4 ± 0.3 mM, 0.3 ± 0.4 mM and 0.0 ± 0.3 mM, being significantly higher on high alkali food (P < 0.05) than in the other groups. Arterial PCO₂, alveolar ventilation and metabolic CO₂ production were not significantly different between groups. On normal and high–alkali chow, an alkaline urine (pH_u > 8.0) with 18–20mmol· kg^–1 bicarbonate/carbonate was excreted daily, typically containing an insoluble precipitate of 35–60% carbonate. On low–alkali diet, the mean pH_u decreased to 6.26 ± 0.14, due to a strong reduction of daily excreted soluble bicarbonate and precipitated carbonate to 1.2 ± 0.6 and 0.7 ± 0.2mmol· kg^–1, respectively. Thereby, nearly complete fractional base reabsorption of 97.8 ± 0.7 % was reached. Conclusion Herbivore nutritional alkaliload elicited large rates of renal base excretion including precipitates, to which the urinary tract of the rabbits appeared to be adapted. Dietary base variations were more accurately reflected in the urine than by the blood acid–base status. A strongly base–deficient diet exerted maximum impact on renal base saving mechanisms, implying a critical precondition for growing susceptibility to metabolic acidosis also in the rabbit.     

Identifying occupational and nonoccupational exposure to mercury in dental personnel

The objective of this study was to investigate the occupational and nonoccupational exposure to mercury (Hg) vapor in dental personnel by examining the relationships between blood mercury, urine mercury, and their ratio with air mercury. The method was performed on 50 occupational exposed and 50 unexposed controls (25 men and 25 women). The mercury concentrations in air and human biological samples were determined based on the National Institute for Occupational Safety and Health (NIOSH) method and standard method (SM) by a new mode of liquid-phase microextraction, respectively. The mean mercury concentrations in urine (μg Hg⁰/g creatinine) and blood were significantly higher than control group, respectively (19.41 ± 5.18 vs 2.15 ± 0.07 μg/g and 16.40 ± 4.97 vs 2.50 ± 0.02 μg/L) (p <.001). The relationships between mercury concentration in blood/urine ratio (r = .380) with dental office air are new indicators for assessing occupational exposure in dental personnel.     

Preferential Liver Accumulation of Mercury Explains Low Concentrations in Muscle of Caiman yacare (Alligatoridae) in Upper Amazon

Caiman yacare is considered one of the top predators in the Amazon basin, and understanding pollutant distribution within its tissues may help its sustainable management. As a top predator, C. yacare should have the highest mercury concentrations, but has lower Hg concentrations than carnivorous fish (Rivera et al. 2016), which are part of their diet. We compared total Hg among liver, kidney, fat, and muscle of C. yacare, and whether trends in the distribution of Hg among tissues were like other crocodilians, aquatic birds, omnivorous, and carnivorous fish. Fat had the lowest concentrations (0.025 ± 0.03 mg kg⁻¹) followed by muscle (0.15 ± 0.06 mg kg⁻¹), kidney (0.57 ± 0.30 mg kg⁻¹) and liver (1.81 ± 0.80 mg kg⁻¹). Such preferential accumulation makes C. yacare meat a safer alternative for human consumption than carnivorous fish. The relation between Hg accumulation in liver and muscle is highest in crocodilians, which has evolutive and environmental implications.

     

Occurrence of methylated mercury in a terrestrial food chain

The presence and transfer of methylated mercury (MeHg) in a terrestrial food chain were determined by radiotracer laboratory experiments and chemical analyses of field-collected organisms. [²⁰³Hg]MeHg-tagged fescue grass (Festuca sp.) at 0.65 μg MeHg/g grass (wet wt) was fed to cotton rats (Sigmodon hispidus). The rats had an assimilation efficiency (A_e) for MeHg of 99% and a biological half-life (t_b) of 9.5 days. Control S. hispidus and Festuca collected from the same populations as the experimental organisms were analyzed for MeHg and found to have, for the S. hispidus, 1.4 ± 0.2 ng/g, 1 SE, and 1.3 ± 0.3 ng/g, 1 SE, in skeletal muscle and liver, respectively; and, for Festuca (composite sample) 0.6 ng/g. Total mercury (ΣHg) for the same tissues was 119.4 ± 39 ng/g, 1 SE, 34.6 ± 8.9 ng/g, 1 SE; and 71 ng/g (composite sample), respectively. Calculations with the experimental and analytical MeHg values indicated that the feral S. hispidus would, at equilibrium, have a whole-body MeHg concentration of 1.89 ng/g. These results, compared with literature reports, indicate that feral rodents have concentration ranges of ～50 to ～160 ng/g for ΣHg, and ～1 to ～7 ng/g for MeHg. Environmental levels of mercury are likely to increase significantly; further environmental measurements and especially appropriate toxicity tests are warranted to assess the importance of MeHg in terrestrial ecosystems.     

Biliary excretion of 203Hg, 64Cu, 52Mn, and 210Pb in the rat

Cikrt, M. (1972).Brit. J. industr. Med.,29, 74-80. Biliary excretion of ²⁰³Hg, ⁶⁴Cu, ⁵²Mn, and ²¹⁰Pb in the rat. The biliary excretion of ⁵²Mn, ⁶⁴Cu, ²⁰³Hg, and ²¹⁰Pb after intravenous adminstration of ⁵²MnCl₂, ⁶⁴CuCl₂, ²⁰³HgCl₂, and ²¹⁰Pb (NO₃)₂ in non-toxic doses was studied in rats. Cumulative biliary excretion reached by 24 hours after administration in the case of ⁶⁴Cu 31·06%, of ⁵²Mn 26·7%, of ²⁰³Hg 3·8%, and of ²¹⁰Pb 6·7% of the administered dose. The excretion curve for ²⁰³Hg differed significantly from those of the other three metals. The maximum rate of excretion was reached at different periods after administration for each metal. The excretion of the metals via the wall of the gastrointestinal tract during 24 hours after administration was also studied. The excretion into faeces occurred mainly via the bile; to a lesser extent there was excretion through the wall, probably chiefly of the upper segments of the digestive tract.     

Uptake, distribution, and fate of 203Hg-ethylmercuric chloride in the guppy and the coontail

The guppy (Lebistes resticulatus) and coontail (Ceratophyllum demersum) were exposed to water containing ²⁰³Hg-labeled ethylmercuric chloride (EMC). The EMC uptake was related to the time of exposure and the concentration of EMC. Highest concentration of ²⁰³Hg was found in the internal organs of the guppy and the body has the least concentration. The biological half-life of ²⁰³Hg from EMC was approximately between 20 and 23 days. Both organisms are capable of converting the absorbed EMC to inorganic mercury with the coontail having a slightly higher rate (34%) of conversion as compared to the average of 29% for the guppy during a seven-day period.Both organisms accumulated slightly more MMC than EMC from a solution containing the same concentration of EMC or MMC. There was very little conversion of MMC to inorganic mercury by the guppy, indicating the stability of MMC in this organism. The absorbed MMC molecule was also more stable than the EMC in the coontail.     

The Effect of Maternal Dose on Lead Retention in Suckling Rats

Lead (Pb) transfer from mother to litter was investigated at the late stage of lactation after a single intraperitoneal injection of 2.0 μg Pb/ml marked with ²⁰³Pb . After 48 hr almost 20% of the maternal dose of ²⁰³Pb was found in the litter, and about 0.6 and 0.2% of the injected dose was found in the liver and kidneys of suckling rats, respectively. Similar whole-body retention was observed earlier in suckling rats after a 20 times lower dose of stable lead was injected intravenously into their mothers.     

Renal and Electrolyte Effects of Total Parenteral Nutrition

Effects of short-term (4–14 days) total parenteral nutrition on renal handling of water and electrolytes were studied retrospectively in 24 patients and prospectively in eight patients. There was 33% incidence of hyponatremia and significant reductions in serum creatinine (from 1.03 ± 0.06 to 0.88 ± 0.06 mg/dl, p < 0.001), phosphorus (from 3.2 ± 0.14 to 2.5 ± 0.17 mg/dl, p < 0.005) and uric acid (from 6.09 ± 0.38 to 3.66 ± 0.24 mg/dl, p < 0.001) were observed. Hypouricemia correlated with increased fractional excretion of urate (r = —0.81,p < 0.05). Hypophosphatemia was associated with increased tubular reabsorption of phosphate. Clearance studies in eight patients showed high urine flow rate (1.7 ± 0.2 ml/min), osmolar clearance (3.2 ± 0.7 ml/min), urinary nonelectrolyte, nonurea solute excretion (0.23 ± 0.14 mmol/min), and negative free water clearance (T^cH₂O = 1.5 ± 0.6 ml/min). These data suggest presence of compartmental shifts, expanded extracellular fluid volume, and possible direct effects on renal tubular transport functions during total parenteral nutrition. (Journal of Parenteral and Enteral Nutrition 8:546–551, 1984)     

Biological monitoring of metals in children and pregnant women in Poland

A pilot study was carried out on the concentration of cadmium, lead, mercury and selenium in blood and urine from 15 first grade school children, 7–8 years of age, living in Katowice‐Szopienice (Silesian Region), and eight pregnant women living in Krakow. The two Polish communities have high levels of pollution from the metallurgic and coal industry. The concentrations of lead in blood for the children ranged from 77 to 255 µg Pb 1^?1 with a median (Md) of 163 µg Pb 1^?1 and for the women from 32 to 64 µg Pb 1^?1 with a Md of 38 µg Pb 1^?1 The high lead levels in blood among the children were related to the distance from their home to a smelter. The analysis of lead in urine also identified the children with the highest levels of exposure. The median levels of cadmium in blood were for children 0.5 µg Cd 1^?1 and for women 0.7 µg Cd 1^?1 and in urine 0.4 µg Cd 1^?1 for children and 0.5 µg Cd 1^?1 for women. Mercury levels in blood were below 4 µg Hg 1^?1 in both groups. The concentrations of selenium in plasma and blood were low and for children the range in blood was 57 to 79 µg Se 1^?1 with a Md of 64 µg Se 1^?1. The selenium in blood for the pregnant women ranged from 30 to 86 µg Se 1^?1 with a Md of 50 µg Se 1¹.