Kidney Tissue Concentrations Research Articles

Nephrotoxicities of aluminium and/or cadmium-metallothionein in rats: creatinine excretion and metabolism of selected essential metals.

The effects of exposure to aluminium (Al) and cadmium (Cd) on urinary creatinine and protein excretion, and the concentrations of calcium, magnesium and copper in kidney and urine were studied in 32 male adult Wistar rats. The animals were divided into 8 groups, groups 1-4 given a calcium-deficient diet (0.01%, i.e. 0.01 g calcium/100 g diet weight) and groups 5-8 a calcium-adequate diet (0.9%) for 6 weeks. Single daily intraperitoneal injections of AlCl3 (10.8 mg Al/kg body weight, per day) were done on 6 consecutive days to groups 3, 4, 7 and 8 during the last week of the experiment. One single intraperitoneal injection of cadmium-metallothionein (Cd-MT, 0.4 mg Cd/kg) was administered 12 hr before the final Al dose to groups 2, 4, 6, and 8 and the rats were sacrificed 47 hr after the Cd-MT injection. The rate of creatinine clearance was significantly lower in rats injected intraperitoneally with either Cd-MT or Al, and the concentrations of magnesium and calcium in urine were lower in rats administered both Al and Cd-MT as compared to those in control groups. Histological examination showed that Al was toxic to the kidney tubule cells of rats, however, an adequate supply of calcium in food protected to some extent the renal tubules from Al toxicity as indicated by a higher creatinine clearance, and there was also less tubule damage as shown by histological examination. The copper concentrations in kidney tissue were lower in groups treated with either Al or Cd-MT.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits.

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200,000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13-18 groups (n = 5-10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6-1.4, 4.7-9.0, 4.5-18.9, 1.8-3.1, 0.9-3.0, 3.4-9.6, 5.0-16.1 and 7.4-12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 microgram/g in various tissues ranged from 5.0-11.6, 70.0-110.5, 114.0-179.8, 21.3-30.3, 4.1-24.8 and 47.8-84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.

Zinc, cadmium, mercury and selenium in polar bears (Ursus maritimus) from Central East Greenland

Muscle, liver, and kidney tissues from 38 polar bears (Ursus maritimus) caught in the Scoresby Sound area, Central East Greenland, were analysed for zinc, cadmium, mercury and selenium. In general, cadmium concentrations were low in muscle, liver and kidney tissue, with geometric means (g.m.) of 0.022 (range: <0.015–0.085), 0.841 (range: 0.092–3.29) and 13.1 (range: 1.04–115) μg Cd/g wet weight (ww) respectively. This finding can be explained by low cadmium levels in the blubber of ringed seals. The concentration of mercury in muscle tissue was low (g.m. 0.071; range: 0.039–0.193 μg Hg/g ww), whereas concentrations in liver and kidney tissue were relatively high (liver: g.m. 7.87; range: 1.35–24.8 μg Hg/g ww, and kidney: g.m. 15.2; range: 1.59–66.6 μg Hg/g ww). Mercury and cadmium were positively correlated with age in liver and kidney. Zinc was positively correlated with age in kidney, and selenium was correlated with age in liver. Contrary to other marine mammals, polar bears had higher mercury levels in the kidneys than in the liver. In all three tissues polar bears had significantly lower cadmium levels than ringed seals from the same area. Mercury levels were likewise significantly lower in the muscle tissue of polar bears than in ringed seals, whereas levels in the liver and kidney were significantly higher. The previous geographic trend for cadmium and mercury found in Canadian polar bears could be extended to cover East Greenland as well. Hence cadmium levels were higher in Greenland than in Canada, while the opposite was the case for mercury. Greenland polar bears had higher mercury and cadmium contents in livers and kidneys than polar bears from Svalbard. The mercury levels in muscle and liver tissue from polar bears from East Greenland were twice as high as found in bears from western Alaska, but half the levels found in northern Alaska. Cadmium and zinc were partially correlated in kidney tissue, and this was found for mercury and selenium as well. Cadmium and zinc showed molar ratios close to unity with the highest concentrations occurring in kidney tissue, while the levels of zinc exceeded cadmium in muscle and liver tissue by up to several decades. Mercury and selenium showed molar ratios close to unity in liver and kidneys.

Metabolism of Pyriproxyfen in Rats. 1. Absorption, Disposition, Excretion, and Biotransformation Studies with [phenoxyphenyl-14C]Pyriproxyfen

Male and female rats were given a single oral dose of [phenoxyphenyl- 14 C]pyriproxyfen [4-phenoxyphenyl (R,S)-2-(2-pyridyloxy)propyl ether] at 2 (low dose) or 1000 (high dose) mg/kg. 14 C was rapidly excreted into feces and urine, with the former route predominating (about 90% of the dose). Peak 14 C concentrations in blood, kidney, liver, and other tissues except for fat occurred 2-8 h after administration, being 0.4, 0.4, 2.5, and <0.2 μg of pyriproxyfen equivalents/g of tissue (ppm), respectively. Peak 14 C concentration in fat occurred 12-24 h after administration, being 0.3-0.5 ppm. 14 C tissue residues on the seventh day were below 0.02 and 10 ppm for the low and high doses, respectively. The major metabolic reactions were hydroxylation at the 2- or 4-position of the terminal phenyl ring, hydroxylation at the 5-position of the pyridyl ring, cleavage of the ether linkages, and conjugation of the resultant phenols with sulfuric acid. No marked sex-related differences were observed for 14 C excretion or 14 C tissue residues. However, a slight sex-related variation was found for the extent of metabolic reactions

Mercury Levels in Michigan River Otters,Lutra canadensis

ABSTRACT Mercury (Hg) concentrations were examined in kidney and/or liver tissues of 43 river otters collected from the upper and northern lower peninsulas of Michigan from 1987–1989. In general, Hg concentrations in Michigan's otters were lower than reported for other localities in the United States but higher than concentrations reported in Michigan fish species. Concentrations were significantly higher in liver tissue relative to kidney tissue, averaging 2.18 mg Hg kg−1 dry weight ± 0.25 (S.E.) in the liver and 1.50 mg Hg kg−1 dry weight ± 0.22 in the kidney. Hg concentrations in liver and kidney tissues were significantly correlated (r = 0.41, p < 0.05). When the data were pooled for all years. Hg concentrations in liver tissue were statistically (94%) higher in males than females. Additionally. Hg concentrations in kidney tissue were 18.5% higher in males than females. but this difference was not statistically significant. No statistically verifiable relationships were noted between Hg concentrations...

Increased insulin-like growth factor-II tissue concentrations during compensatory kidney growth in infantile rats.

Insulin-like growth factor (IGF)-I and IGF-II serum and kidney tissue concentrations were measured in compensatory kidney growth in infantile and adult rats. We hypothesized that the known switch from IGF-II in fetal life to IGF-I in adult life may be responsible for the different modes of compensatory kidney growth, which are mainly characterized by hyperplasia in infantile rats and hypertrophy in adult rats. While IGF-I serum concentrations increased with age in infantile rats, kidney tissue concentrations of IGF-I showed a similar increase in both age groups after uninephrectomy. In adult rats, serum and kidney tissue concentrations of IGF-II were unchanged by uninephrectomy. In infantile rats, however, a significant increase in both serum and kidney concentrations of IGF-II was observed with a maximum at day 5 after uninephrectomy. To investigate if compensatory kidney growth is dependent on hyperperfusion of the remnant kidney, the left renal artery was clipped in infantile rats. The clipped kidney showed growth retardation despite normal kidney tissue concentrations of IGF-I and IGF-II. The contralateral kidney was enlarged and IGF-II kidney concentrations were elevated. However, animals with one clipped kidney and nephrectomy of the contralateral kidney showed compensatory kidney growth of the clipped kidney combined with increased IGF-II kidney tissue concentrations. We conclude that IGF-II mainly promotes compensatory kidney growth in infantile rats by hyperplasia. Hyperperfusion of the remnant kidney seems to be unnecessary for initiation of compensatory kidney growth.

Stable isotope labeling of lead compartments in rats with ultralow lead concentrations

The role of the mammalian skeleton as an endogenous lead source is unclear. This is due in part to difficulties in distinguishing mobilized skeletal lead from other endogenous and exogenous lead sources. Therefore, we have applied ultraclean stable lead isotope techniques to label skeletal and soft tissue lead compartments within the rat with distinguishable lead isotopic signatures. Female Wistar (defined flora) rats were fed 206Pb-enriched drinking water ([Pb] = 110 ng/ml) and sacrificed after durations of 2, 4, 7, and 14 days. Blood, kidney, vertebra, and tibia tissues were analyzed for lead concentrations and stable isotopic compositions. The resulting isotopic ratios in soft (blood and kidney) and skeletal (vertebrae and tibia) tissues differed by approximately 40% after 2 days exposure to the 206Pb tracer. More than 90% of the tracer isotopic signature was contained in the soft tissues after 10 days exposure, while skeletal tissues acquired only approximately 50% of the tracer by the end of the study. Because these animals were maintained under trace metal-clean conditions, they contained lead concentrations in whole blood (0.3-3 ng/g), kidney (11-27 ng/g dry wt), and bone (35-70 ng/g dry wt) tissues that are the lowest known reported for contemporary terrestrial mammals, and they (in bone) are comparable to levels in preindustrial mammals. The elevated concentrations of lead in kidney (fresh weight) relative to levels in blood are consistent with the presence of specific lead-binding sites in the kidney at very low levels of exposure.

Mercury determination by cold vapour atomic absorption spectrometry in several biological indicators from Lake Maracaibo, Venezuela.

Two sampling sessions were carried out in Lake Maracaibo and eight sites selected in four pairs one in front of the other (El Moján-Ancón de iturre, Santa Cruz de Mara-Punta de Palmas, Maracaibo-Punta de Leiva and San Francisco-La Rita). Specimens of Cynosción acoupa Maracaiboencis (curvina, n = 5), Oligoplites palometa (palometa, n = 5), Penaeus schmitti (shrimp, n = 20), and Polymesoda arctata (mussels, n = 20) were collected. For the curvina and palometa, muscle, brain, kidney, gill, liver and heart were analysed. Shrimp and mussels were analysed whole, without the shells. Samples were lyophilized and cold digested in a mixture of sulfuric, nitric and perchloric acids, potassium permanganate and hydrogen peroxide. Spectrometric determination was carried out using cold vapour atomic absorption spectrometry and sodium borohydride as reducing agent. Accuracy was tested with a National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) RM50 Albacore Tuna, and against another method. The detection limit for Hg was 53 ng l-1. Good agreement was found between results for the analysis of SRM RM50 (Hg = 0.95 +/- 0.14 mg kg-1) and the assigned value furnished by NIST (Hg = 0.95 +/- 0.10 mg kg-1). Precision and the interference were also evaluated. Mercury concentrations in brain, kidney and heart tissues of the curvina and palometa were found to be higher than those in the muscle tissue.

Multielement Concentrations in Liver and Kidney Tissues from Five Species of Canadian Slaughter Animals

The present paper describes results of a national survey conducted between 1982 and 1989 to determine residues of arsenic, cadmium, copper, mercury, lead, selenium, and zinc in Canadian slaughter animals. Liver and kidney tissues from cattle, swine, poultry, horses, calves, and sheep were tested. Arsenic was found in most avian and porcine samples, and their respective means of 0.36 and 0.26 micrograms/g in liver were 7 to 12 times higher than mean concentrations found in the other species. Cadmium was found in the tissues of all species; however, levels were consistently highest in equine samples with mean values of 3.09 and 27.7 micrograms/g in liver and kidney, respectively. Copper levels greater than 150 micrograms/g were found predominantly in liver from calves and sheep, with values considerably lower in the remaining species. Mercury levels were low or not detected in all species except horses. Ninety % of equine kidneys and 54% of equine livers had mercury concentrations greater than 0.01 microgram/g, with mean values of 0.18 and 0.06 microgram/g, respectively. Lead was found in tissues of all species; however, values greater than 2 micrograms/g were found only in 2 kidneys from adult cattle and 1 kidney from a horse. Selenium, tested only in cattle, was found at mean concentrations of 0.28 microgram/g in liver, and 0.92 microgram/g in kidney. Relatively high zinc levels were found in livers of horses, pigs, and calves, with respective mean concentrations of 67.3, 65.6, and 70.2 micrograms/g.

Relation between renal and hepatic excretion of drugs:: XV. Organ distribution and transport of the new antiarrhythmic drug Bonnecor® in kidney and liver of rats

Following administration of various doses of 14C-labeled Bonnecor (0.15 to 0.6 mg/100 g b.wt. i.v.) renal excretion of 14C-radioactivity dominates and the total rate of excretion both via kidney and liver reaches 60% during 6 h clearance experiment, independent of the administered dose. Otherwise nearly the same concentration of 14C-radioactivity can be measured in kidney and liver tissue. An alpha- und beta-slope of disappearance from the tissue seems to exist. At different times after administration of Bonnecor (0 to 15 h) the concentrations in kidney and liver tissue are distinctly higher compared with plasma concentrations. In vitro experiments on tissue slices confirm a nearly identical degree of accumulation of 14C-radioactivity in liver and kidney. In renal cortical slices the high degree of accumulation depends on active tubular transport processes. Comparing accumulation in liver slices under aerobic and anaerobic conditions a preferential passive uptake of Bonnecor can be demonstrated. Efflux kinetics in slices from liver and kidney cortex is in accordance with this interpretation.

A Death due to Self-Administered Fentanyl

A fatality resulting from the self-administration of fentanyl is described. The decreased was a health care professional with a known history of drug abuse. At the scene, a syringe partly filled with red fluid was found. Pathological findings disclosed pulmonary congestion, hemorrhage, and aspiration of gastric contents and passive congestion in the liver and kidneys. Initial drug screening revealed the presence of fentanyl in the fluid from the syringe and diazepam/oxazepam in the urine. Fentanyl, diazepam, nordiazepam, and oxazepam in the submitted samples were simultaneously quantitated using a gas chromatograph equipped with a nitrogen-phosphorus detector. The fentanyl concentrations (micrograms/L or micrograms/kg) in serum, blood, urine, bile, liver, kidney, brain, lung, and stomach tissue were 17.7, 27.5, 92.7, 58.2, 77.5, 41.5, 30.2, 83.4, and 31.6, respectively. The tissue levels of diazepam and its metabolites were lower than the reported lethal concentrations. The fentanyl concentration in the syringe contents was 2,800 micrograms/L. The toxicological findings and circumstantial evidence of the case indicate that the death resulted primarily from fentanyl overdose.

Determination of gold accumulation in human tissues caused by gold therapy using x-ray fluorescence analysis

Human autopsy tissues from five patients with rheumatoid arthritis, who had been treated with aqueous solutions of gold and from an untreated control cadaver with the same disease, were analysed by x-ray fluorescence spectrometry using a conventional Si(Li) detection system. The gold and zinc concentrations of tissues were determined and compared to some results available in the literature. Correlation has been found between Zn and Au concentrations in heart, lung, kidney and liver tissues.

Mercury levels in Bonaparte's gulls (Larus Philadelphia) during autumn molt in the Quoddy region, New Brunswick, Canada

No significant between sex differences were detected in Hg concentrations in primary feathers, pectoral muscle, brain, liver, and kidney tissues of fall migrating juvenile and second-year Bonaparte's gulls (Larus Philadelphia) collected in the Quoddy region. Adults showed sexual differences only in the first 5 primary feathers, and in muscle, kidney and brain. Differences in Hg concentrations among age groups were reflected in the primary feathers and body tissues, but as the molt progressed, Hg concentrations decreased as they converged toward a minimum asymptotic Hg level for each tissue. This suggests that the body burden of Hg was reduced through its redistribution from the body tissues into the growing feathers. Mercury concentrations in premolt head feathers (pre-egg-laying) did not vary significantly between adult females and males, whereas Hg concentrations in postmolt feathers (post-egg-laying) were significantly lower in females, suggesting that egg-laying was also a route for Hg elimination. After the completion of the molt, the new feathers contained most of the body burden of Hg (93.0% in adults).

Norfloxacin penetration into human renal and prostatic tissues

Concurrent norfloxacin concentrations in serum, kidney, and prostatic tissue were determined in 14 patients. Mean ratios of norfloxacin concentration in tissue over concentration in serum were 6.6 +/- 2.8 for the kidney and 1.7 +/- 0.2 for the prostate samples. The levels were above the MICs of most urinary pathogens.

Tin distribution in adult rat tissues after exposure to trimethyltin and triethyltin

The time course of distribution of tin in the adult rat was determined in brain, liver, kidneys, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1, 4, 12, and 24 hr, and at 5, 10, or 22 days following injection of TMT and TET ( N = 6/time), and tissues were analyzed for total tin by atomic absorbance spectroscopy. TET exposure resulted in higher tin concentrations in brain, liver, and kidney tissues, while the two trialkyltins resulted in approximately equal tin concentrations in the heart and blood. Rates of elimination of tin (expressed as elimination rate constants, K el) were greater in all tissues following TET exposure than following TMT exposure. The concentration of tin in the brain 12 hr after TMT exposure was 4.4, 8.5, and 12.7 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across the cerebellum, medulla-pons, hypothalamus, hippocampus, and striatum following TMT exposure. These results describe major differences in the disposition and rates of elimination of tin from body tissues after TMT and TET exposure, and demonstrate that the regional disposition of tin is not related to the region-specific pathology reported following TMT exposure.

Chromium, cobalt and lanthanum in lung, liver and kidney tissue from deceased smelter workers

Lung, liver and kidney tissue concentrations of chromium, cobalt and lanthanum from 66 deceased copper smelter workers have been compared with 14 controls. Samples were taken in connection with ordinary autopsies at the local hospital. Neutron activation analysis was used. The mean exposure time for the smelter workers was 30 y, the mean time to date of death after termination of exposure was 7.4 y. A four-fold increase of chromium ( p = 0.001) and a two-fold increase of cobalt ( p < 0.001) and lanthanum ( p = 0.013) in lung tissue was found for smelter workers compared to controls. Of the smelters nearly one third died from malignancies (∼10% from respiratory cancer) and ∼45% from cardiovascular diseases. In the control group nearly 80% died from cardiovascular diseases and no malignancies were found. In lung tissues the concentration of chromium, cobalt and lanthanum did not decline with time after exposure had ended, indicating a long biological half-time. The causes of death could not be related to a single factor. The findings indicate a multifactorial genesis.

Heavy Metal Concentrations in Muscle, Liver and Kidney Tissue of Striped Dolphin,Stenella coeruleoalba, and Their Variations with Body Length, Weight, Age and Sex

The concentrations of Fe, mn, Zn, Cu, Pb, Ni, Cd and Hg in the muscle, liver and kidney of fifty nine striped dolphins captured during 1977 ~ 1980 were determined by atomic absorption spectrophotometry. The levels of most the metals examined were higher in the liver than the other tissues, except for the highest renal Cd. The frequency distribution of the metal concentrations was mostly log-normal. For all of the organs, correlation of the metal concentrations to the body length, weight and age was positive for Fe, Pb, Ni, Cd and Hg, and negative for Mn, Zn and Cu. A higher correlation of the concentrations of Fe, ??, Zn and Cu to the body length and weight than to the age indicates that the metabolic turnover is more important than age or exposure time in determining the levels of those metals. Whilst the concentration of Pb, Ni, Cd and Hg correlated closely with the age of dolphins, and this suggests that the age or exposure time is a dominant factor for accumulation of these metals.The concentrations o...

Heavy metal concentrations in muscle, liver and kidney tissue of striped dolphin, Stenella coeruleoalba, and their variations with body length, weight, age and sex.

The concentrations of Fe, Mn, Zn, Cu, Pb, Ni, Cd and Hg in the muscle, liver and kidney of fifty nine striped dolphins captured during 1977- 1980 were determined by atomic absorption spectrophotometry. The levels of most the metals examined were higher in the liver than the other tissues, except for the highest renal Cd. The frequency distribution of the metal concentrations was mostly log-normal. For all of the organs, correlation of the metal concentrations to the body length, weight and age was positive for Fe, Pb, Ni, Cd and Hg, and negative for Mn, Zn and Cu. A higher correlation of the concentrations of Fe, Mn, Zn and Cu to the body length and weight than to the age indicates that the metabolic turnover is more important than age or exposure time in determining the levels of those metals. Whilst the concentration of Pb, Ni, Cd and Hg correlated closely with the age of dolphins, and this suggests that the age or exposure time is a dominant factor for accumulation of these metals. The concentrations of Pb, Ni, Cd and Hg in the muscle, liver and kidney increased with age until 1 year, leveled off through 1 to 18 years by physical dilution with increased body weight, and thereafter steadily increased year by year, but in case of Hg such physical dilution effects were not significant. Relatively wide variation of the metal concentrations in the pup and 8-25 years females was probably due to the effects of suckling, and of parturition and lactation, respectively.

CEMENT KILN DUST IN AN ALL-CONCENTRATE DIET FOR FEEDLOT STEERS

Two groups of 16 steers were fed an all-concentrate diet with or without 3.5% cement kiln dust for 125 days. There were no differences (P &gt; 0.05) in overall animal performance between the two experimental groups. Steers fed the cement dust diet and the control diet gained an average of 1.12 and 1.24 kg/day, respectively. Both groups of cattle ate an average of 9.2 kg of feed daily. There was a significant interaction (P &lt; 0.05) between diet and length of time on feed; the cattle which were fed cement kiln dust ate slightly more than the control group in the first two thirds of the experiment and less in the last third of the experiment. Rate of liveweight gain was also lower (P &lt; 0.05) in the cattle fed cement kiln dust in the last third of the experiment. Lead concentrations in kidney tissues were significantly higher (P &lt; 0.01) in the steers fed the cement kiln dust (0.80 mg/kg, wet weight basis) than in the steers fed the control diet (0.36 mg/kg, wet weight basis). The diets had no significant (P &gt; 0.05) effect on lead concentrations in muscle tissue, blood or liver.

Heavy Metal Residues in Plants Cultivated on and in Small Mammals Indigenous to Old Orchard Soils

Six vegetables and millet were grown on the site of an old orchard which had received heavy applications of lead arsenate and organic mercury fungicides for many years. Carrots and millet absorbed about 7 ppm (dry weight) of lead, the other crops containing smaller concentrations. Concentrations of arsenic and mercury showed only modest increases in crops grown on the orchard soil as compared to controls. Lead concentrations in kidney, liver, and bone tissue of meadow voles trapped in two old orchards were markedly higher (up to 300 ppm in bone) than control animals (up to 33 ppm). Intranuclear inclusion bodies diagnostic of lead poisoning were found in the renal epithelial cells of the proximal convoluted tubules in voles from lead arsenate treated orchards.