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Biomedical subjects

J K Piotrowski

Publications and source records attributed to J K Piotrowski.

At least 19 recordsLinked to original sources
PubMed2000

Hepatotoxicity of tetrabromobisphenol-A: effects of repeated dosage in rats.

Tetrabromobisphenol-A (TBBP-A) is used as a reactive flame retardant and as an intermediate in the production of other flame-retardants. In our study, TBBP-A was administered intragastrically, daily for 7 or 7-28 days at three dose levels. Significant changes of biochemical indicators were noted with regard to glutathione (GSH), malondialdehyde (MDA) and 5-aminolevulinate dehydratase (ALA-D). The level of GSH was lowered by the two higher doses (female rats only) and MDA was elevated by the highest dose (male rats only). The ALA-D activity reacted in opposite directions for both sexes. Other indicators did not yield any conclusive results. The 28-day study was performed on female rats. For GSH and MDA the medium dose resulted in a systematic increase. Insignificant changes in ALA-D activity in the liver were observed throughout the experiment. The activity of 5-aminolevulinate synthase had a decreasing tendency at 250 mg/kg of TBBP-A during the whole time of observation. Other general indices such as the activity of gamma-glutamyltransferase, concentration of microsomal proteins and the level of cytochrome P-450 did not show any significant changes. The most pronounced changes were noted with regard to indicators of porphyrogenic action. The results suggest that TBBP-A is capable of disturbing the heme metabolism in rats.

Animals↗
PubMed2000

Hepatotoxicity of monobromobenzene and hexabromobenzene: effects of repeated dosage in rats.

The aim of the study was to determine whether monobromobenzene (BB) and hexabromobenzene (HBB) administered repeatedly (for 28 days) to female rats resulted in disturbances of heme synthesis. 5-Aminolevulinate dehydratase (ALA-D) and 5-aminolevulinate synthase (ALA-S) activities were slightly changed and the concentration of glutathione increased. The excretion of 5-aminolevulinic acid (ALA-U) in urine after all doses of BB and HBB increased already in the first week. After BB administration, increased excretion of coproporphyrins was detected only at the highest dose. The increased excretion of coproporphyrins following the administration of HBB could be observed already at the lowest dose (15 mg/kg). The excretion of uroporphyrins increased after two higher doses (75 and 375 mg/kg) in the fourth week of exposure. HBB also caused elevation of microsomal P450 level. The data suggest porphyrogenic activity of HBB; whereas in the case of BB we cannot exclude that elevated excretion of ALA-U resulted from kidney impairment.

5-Aminolevulinate Synthetase↗
PubMed2000

Circadian variations in hepatotoxicity of carbon tetrachloride in mice.

Male mice of Balb/C strain were administered i.p. carbon tetrachloride, in single doses of 35 and 145 mg/kg, given at variable time of the day. The activity of alanine aminotransferase (ALAT) in serum, and the hepatic level of malondialdehyde (MDA) as well as reduced glutathione (GSH) were adopted as indicators of toxicity. In selected groups, liver histopathology was carried out. The experiment was performed in two series differing in the dynamics of observations. A differentiation of the intensity of toxic effects was found dependent on the time of the day at which animals were administered the xenobiotic. This was especially evident for a lower dose: given in the morning it produced no effects, whereas given in the evening it resulted in distinct elevation of toxicity indicators. Additionally, the correlation was checked between the histopathological evaluation (semiquantitative expression) and serum ALAT activity. A high correlation (r = 0.98) allows for basing the evaluation of liver necrosis on the ALAT activity alone.

Analysis of Variance↗
PubMed1999

The disposition and metabolism of 1,3-dibromobenzene in the rat.

The distribution, excretion and metabolism of 1,3-dibromobenzene following a single i.p. administration to rats 100 or 300 mg/kg was investigated using radiotracer [3H] and GC-MS technique. After 72 hours about 74 to 90% were excreted in urine. The highest radioactivity was observed in the liver, kidneys and fat tissue. Later on a steady decline of radioactivity was apparent in all investigated tissues except for blood cells and the sciatic nerve, where constant levels were noted. In urine the following substances were identified and quantified by GC peak areas: unchanged 1,3-DBB (18%), dibromophenols (34%), dibromothiophenols (28%), dibromothioanisole (1.8%), bromophenol (5.5%), bromohydroxythiophenols (5%), and bromohydroxythioanisole (7.5%).

Absorption↗
PubMed1998

Metal composition of human hepatic and renal metallothionein.

This article is based on data on the levels of metals (Cd, Zn, Cu) and metallothionein (MT) determined radiochemically with 203Hg in renal cortex and liver of 137 autopsy cases. From this number, for 23 cases, the gel filtration of the cytoplasmic fraction of the organs was performed. The molar content of metals in the MT fraction (Sephadex G-50) amounted to 46.9, 50.2, and 2.0% for Cd, Zn, and Cu in renal cortex, respectively, and to 8.3, 83.6, and 9.1% for Cd, Zn, and Cu in the liver, respectively. In parallel with the increase of Cd and MT in renal cortex, increasing saturation was found of the MT fraction by Cd, occurring at the expense of Zn and Cu. Equimolar amounts of Cd and Zn in the MT fraction are found at Cd level of 0.5 micromol Cd/g wet wt of renal cortex. In the liver, analogous dependency (elevation of %Zn, depression of %Cd and %Cu) were observed in relation to Zn and MT levels in this organ. The basic level of Zn (not bound with MT) was estimated at 0.5 micromol/g for both renal cortex and liver. A deficit of non-MT Zn in kidneys is proposed as an alternative mechanism of toxic Cd action.

Cadmium↗
PubMed1998

Urinary cadmium as indicator of renal cadmium in humans: an autopsy study.

OBJECTIVE: To estimate the equivalent cadmium levels in renal cortex and in urine, as based on autopsy analysis of subjects not exposed to cadmium occupationally. METHODS: The levels of Cd were determined in renal cortex, liver, urine and urinary bladder of 39 subjects deceased at the age 42 +/- 14 years. Flame atomic absorption spectrometry (kidneys, liver) and flameless AAS (urine, bladder) were used. RESULTS: The urinary cadmium level determined post mortem is strongly correlated with the renal Cd levels. Eliminating cases with high urinary proteins and extrapolating from sets of data with elevated urinary protein concentration to its normal range yielded a value of 1.7 microg/g creatinine as equivalent to the renal level of 50 microg/g w.w. CONCLUSIONS: It seems possible to use monitoring data for cadmium in urine and in renal cortex in a coherent way.

Adolescent↗
PubMed1996

The levels of cadmium, zinc and copper in the renal cortex and liver of the inhabitants of the copper basin.

Tissues were analysed from 60 subjects deceased at the age of 18-82 (mean 49 years), inhabitants of the southwestern region of Poland (Legnica Copper Basin). Mean cadmium, zinc and copper concentrations determined by flame AAS were for renal cortex 41.8; 47.8 and 2.3 micrograms Me/g tissue, respectively. The respective levels in the liver were 2.3; 51.6 and 4.6 micrograms Me/g tissue (w.w.). A broad range of cadmium levels was found in renal cortex (4.2-129.3.micrograms/g), with the highest values in the 40-60 age group. The effect of tobacco smoking is more evident than in other countries: 26.3 micrograms/g in non-smokers vs. 54.6 micrograms/g in smokers. Similar proportions were found by computing the whole body burden of cadmium. Compared with other regions of Poland the environmental exposure of humans to cadmium is moderate, however, it is higher than in other European countries.

Adolescent↗
PubMed1995

The diurnal rhythm of hepatotoxic action of chloroform.

Mice were administered with chloroform at 10 a.m., 2 p.m. and 6 p.m. and the signs of hepatotoxicity were measured 18 or 24 hrs later. The levels of alanine aminotransferase (ALT) in serum, and malondialdehyde (MDA) in the liver were higher after the evening administration compared to the morning one. The decrements of reduced glutathione (GSH) levels in the liver followed a similar pattern. It is concluded that the susceptibility of mice to the toxic effect of chloroform follows a circadian rhythm.

Alanine Transaminase↗
PubMed1995

Investigations on acute hepato- and nephrotoxicity of pentabromophenol.

Pentabromophenol (PBP) was administered in a single or repeated doses to mice or in a single dose to rats. Slight changes were noted in the level of SGPT in mice serum and GSH in the liver, with a more pronounced increase of MDA after a single dose. Following repeated administration, gamma-GT and MDA were elevated. The nephrotoxic action of PBP in rats was manifested by the decreased of renal GSH levels, as well as by an increase in protein contents and the number of renal epithelial cells in urine. As a result, limited hepatotoxicity was found only in mice. The nephrotoxicity in rats was comparable with that for 2-bromophenol described earlier.

Acute Disease↗
PubMed1993

Cadmium, zinc, copper, and metallothionein levels in the kidney and liver of inhabitants of upper Silesia (Poland).

The levels of Cd, Zn, Cu and metallothionein (MT) were determined in renal cortex and liver of 75 subjects decreased in the period 1986-1989 in the area of Upper Silesia (Katowice). The mean age of the population studied was 53.6 +/- 14.6 years. The determined levels (mean +/- SD) were: 43.1 +/- 23.5 micrograms Cd/g; 52.5 +/- 17.4 micrograms Zn/g; 2.2 +/- 0.7 microgram Cu/g; 0.80 +/- 0.36 mumol Hg/g in renal cortex and 3.5 +/- 2.5 micrograms Cd/g; 82.8 +/- 34.3 micrograms Zn/g; 4.5 +/- 2.6 micrograms Cu/g; 0.69 +/- 0.44 mumol Hg/g in the liver. The level of Cd in renal cortex was 40% higher in smokers compared to nonsmokers and was independent of the gender. Whole-body retention of Cd was 34.1 +/- 18.5 mg; smoking elevated the value from 27.1 to 38.2 mg. Compared with a similar study made in central Poland (Lódź), a significant difference was found only regarding the level of Zn and MT in the liver, pointing to the possibility that exposure to this element in the region of Upper Silesia may be higher.

Adult↗
PubMed1993

Cadmium, zinc, and copper levels in the kidneys and liver of the inhabitants of north-eastern Poland.

Concentrations of Cd, Zn, and Cu were determined in the renal cortex and the liver of 79 persons who died in 1991 in Białystok and its vicinity. The mean concentrations were: 30.5 +/- 27.7 micrograms Cd/g, 37.6 +/- 18.5 micrograms Zn/g, 2.6 +/- 2.5 micrograms Cu/g, and 2.1 +/- 2.2 micrograms Cd/g, 52.4 +/- 20.5 micrograms Zn/g, 4.0 +/- 2.1 micrograms Cu/g, respectively, in the renal cortex and the liver, at the mean age of 51.1 +/- 19.1 years. Smokers showed almost twice higher Cd levels in the cortex than non-smokers. The mean whole body retention calculated for cadmium was 18.9 +/- 15.9 mg. Smoking increases it by about 60%--from 13.7 mg in non-smokers to 22.8 mg in smokers. In the inhabitants of the investigated region cadmium levels (kidney, liver, whole body retention) were lower than in persons from Lodz and Katowice regions.

Adult↗
PubMed1992

Effects of 3-methylcholanthrene or diethyl maleate on the hepatotoxicity of acetaminophen.

This report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg-1 with or without pretreatment with 3-methylcholanthrene (3MCh) or diethyl maleate (DEM). The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione. Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidation.

Acetaminophen↗
PubMed1992

Intestinal absorption of inorganic mercury in rat.

203Hg-Mercuric chloride was administered intragastrically to female rats. The absorption rate evaluated for a broad range of doses was found constant for low and medium range, and higher for high doses. Mercury was determined in internal organs and intestines. The time-course of intestinal mercury indicated that a deposit formed initially in the mucosa was further absorbed into the circulation. No indication was found of a protection mechanism based on exfoliation of the mucosal deposits of metal.

Animals↗
PubMed1991

Protective effect of zinc in the hepatotoxicity of bromobenzene and acetaminophen.

Mice of the Balb'c strain were administered bromobenzene (BB) or acetaminophen (AA) i.p., in single doses of 400 and 300 mg/kg, respectively. In the blood activity of SGOT and SGPT as well as SDH was determined. In the liver the level of metallothionein (MT), malondialdehyde (MDA) and glutathione (GSH) was measured. The level of MT as well as GSH (determined as non-protein SH groups) showed a significant increase following administration of zinc alone. Joint action of zinc and either BB or AA resulted in a decrease of GSH which was less pronounced than expected for each of the xenobiotics alone. The protective effect of zinc reflected in the reduction of the increase of SGPT and SGOT activity was apparent shortly (4 h) after administration of AA. A day after injection of AA alone the activity of enzymes was lower and the rate of decline followed the sequence SGPT greater than SGOT greater than SDH. For BB, both the toxic effect and the protective influence of zinc were apparent 24 h following administration. At 4 h in a group receiving BB alone no changes of the indicatory enzymes in blood were noted.

Acetaminophen↗
PubMed1991

The hepatotoxic action of chloroform: short-time dynamics of biochemical alterations and dose-effect relationships.

Chloroform was administered ip to Balb/c mice as a single dose ranging from 1/8 to 1 of the approximate lethal dose. At different time periods after administration, mice were sacrificed. Serum glutamate-pyruvate transaminase (SGPT) and sorbitol dehydrogenase (SDH) as well as glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Increased SGPT and SDH levels were found for all doses exceeding 1/8 of the approximate lethal dose. The depletion of GSH level was kept within 40% for all doses. A 2-4 fold increase of hepatic MDA level was found. The depletion of hepatic GSH and, to some extent the increase of serum SGPT and SDH, occurred in biphasic fashion. Dose-effect functions for these biochemical alterations could only be constructed for the second, delayed phase of action. It is postulated that the hepatotoxicity of chloroform is mainly dependent on radical formation in the course of biotransformation.

Alanine Transaminase↗
PubMed1991

Toluene determination in capillary blood as a biological indicator of exposure to low levels of toluene.

The possibility of evaluating occupational exposure to toluene at low levels (50-150 mg/m3), based on the determination of unchanged substances in capillary blood, was investigated. The volunteers were exposed in a toxicological chamber; during and after exposure venous and capillary blood samples were analysed by gas chromatography using the headspace technique. Toxicokinetic data point out that determination of toluene should be performed in blood samples collected 15-20 min after termination of exposure. The toluene concentration in capillary blood may reflect the toluene dose absorbed during the workshift only in the case of constant exposure. Otherwise, this measurement refers to the rate of toluene absorption, mainly in the last 2 hours of daily exposure.

Adult↗