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1.
Int J Occup Environ Med ; 6(2): 113-21, 2015 04.
Article in English | MEDLINE | ID: mdl-25890605

ABSTRACT

BACKGROUND: Controversy exists as to the potential of asphalt fumes to induce respiratory symptoms and lung functional impairments. OBJECTIVE: To examine the respiratory effects, if any, of occupational inhalation exposure to asphalt fumes. METHODS: In this cross-sectional study, 74 asphalt workers and 110 unexposed employees were investigated. The prevalence of respiratory symptoms among subjects was investigated by a standard questionnaire. Additionally, the parameters of pulmonary function were measured both, prior to exposure and at the end of work-shift. Furthermore, to assess the extent to which workers were exposed to asphalt fumes, total particulate and the benzene-soluble fraction were measured in different worksites. RESULTS: The mean levels of exposure to total particulate and benzene-soluble fraction in asphalt fumes were estimated to be 0.9 (SD 0.2) and 0.3 (SD 0.1) mg/m^3, respectively. Mean values of FEV1, both prior to the exposure (89.58% [SD 18.69%] predicted value) and at the end of shift (85.38% [SD 19.4%]), were significantly (p<0.05) smaller than those of the comparison subjects (93.88% [SD 13.93%]). Similarly, pre-shift (87.05 [SD 8.57]) and postexposure (89.95 [SD 6.85]) FEV1/FVC ratio were both significantly (p<0.01) lower than those of the unexposed employees (107.56 [SD 9.64]). Moreover, the prevalence of respiratory symptoms such as cough and wheezing in exposed employees were 41% and 42%, respectively. The corresponding values for comparison subjects were 10.0% and 3.6%, respectively (p<0.001). The pattern of changes in parameters of lung function in asphalt workers was consistent with that of chronic obstructive lung disease. CONCLUSION: Significant decrements in the parameters of pulmonary function as well as, a significant increase in the prevalence of respiratory symptoms in asphalt paving workers compared to their unexposed counterparts provided evidence in favor of a significant association between exposure to asphalt fumes and lung function impairments.


Subject(s)
Hydrocarbons/toxicity , Inhalation Exposure/adverse effects , Occupational Exposure/adverse effects , Particulate Matter/analysis , Respiratory Tract Diseases/chemically induced , Adult , Benzene , Cough , Cross-Sectional Studies , Female , Humans , Inhalation Exposure/analysis , Male , Occupational Exposure/analysis , Respiratory Function Tests
2.
Int J Occup Environ Med ; 6(1): 41-9, 2015 01.
Article in English | MEDLINE | ID: mdl-25588225

ABSTRACT

BACKGROUND: Workers in wastewater treatment plants are exposed to a wide range of chemicals as well as biological contaminants. OBJECTIVE: To ascertain whether exposure to bio-aerosols under the normal working conditions in wastewater treatment plants is associated with any significant changes in the prevalence of respiratory symptoms and lung function capacities. METHODS: 198 employees of wastewater treatment plants and 99 unexposed persons were studied. American thoracic society (ATS) standard respiratory symptom questionnaire was used to determine the prevalence of respiratory symptoms. Pulmonary function tests were conducted for each participant. RESULTS: The prevalence of respiratory symptoms among exposed persons was significantly higher than that of unexposed people. Mean values of most pulmonary function test parameters were significantly lower in the exposed compared to the comparison group persons. CONCLUSION: Increased prevalence of respiratory symptoms and decrements in pulmonary function test parameters may be attributed to exposure to bio-aerosols released from wastewater treatment plants.


Subject(s)
Aerosols/adverse effects , Inhalation Exposure/adverse effects , Lung/drug effects , Occupational Exposure/adverse effects , Respiration Disorders/etiology , Wastewater/microbiology , Water Microbiology , Adult , Bacteria , Female , Fungi , Humans , Inhalation Exposure/analysis , Iran/epidemiology , Male , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Occupational Diseases/microbiology , Occupational Exposure/analysis , Prevalence , Respiration Disorders/epidemiology , Respiration Disorders/microbiology , Respiratory Function Tests , Surveys and Questionnaires , Water Purification
3.
Int J Occup Environ Med ; 5(2): 101-5, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24748001

ABSTRACT

Mercury is among the most toxic nonradioactive elements which may cause toxicity even at low doses. Some studies showed release of mercury from dental amalgam fillings in individuals who used mobile phone. This study was conducted to assess the effect of high-field MRI on mercury release from dental amalgam filling. We studied two groups of students with identical tooth decays requiring a similar pattern of restorative dentistry. They were exposed to a magnetic flux density of 1.5 T produced by a MRI machine. 16 otherwise healthy students with identical dental decay participated in this study. They underwent similar restorative dentistry procedures and randomly divided into two groups of MRI-exposed and control arms. Urinary concentrations of mercury in the control subjects were measured before (hour 0) and 48 and 72 hrs after amalgam restoration, using cold vapor atomic absorption spectrometry. Urinary concentrations of mercury in exposed individuals were determined before (hour 0), and 24, 48, 72 and 96 hrs after amalgam restoration. Unlike control subjects, they underwent conventional brain MRI (15 min, 99 slices), 24 hrs after amalgam restoration. The mean±SD urinary mercury levels in MRI-exposed individuals increased linearly from a baseline value of 20.70±17.96 to 24.83±22.91 µg/L 72 hrs after MRI. In the control group, the concentration decreased linearly from 20.70±19.77 to 16.14±20.05 µg/L. The difference between urinary mercury in the exposed and control group, 72 hrs after MRI (96 h after restoration),was significant (p=0.046). These findings provide further support for the noxious effect of MRI (exposure to strong magnetic field)and release of mercury from dental amalgam fillings.


Subject(s)
Dental Amalgam/chemistry , Dental Restoration, Permanent/adverse effects , Electromagnetic Fields/adverse effects , Magnetic Resonance Imaging/adverse effects , Mercury/urine , Adult , Dental Amalgam/adverse effects , Female , Humans , Male , Spectrophotometry, Atomic , Young Adult
4.
Iran Red Crescent Med J ; 14(9): 549-57, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23115717

ABSTRACT

BACKGROUND: Although dolomite is classified as a relatively non-toxic, nuisance dust, little information exists as to its potential to produce respiratory disorders following occupational exposure. The purpose of this study was, therefore, to evaluate the possible effects, if any, of heavy inhalation exposure to this chemical on the prevalence of respiratory symptoms, functional impairments and radiographic abnormalities of the lungs. METHODS: The study population consisted of a group of 39 exposed subjects engaged in digging and excavating activities that were in operation for building a local dam, as well as 40 healthy non-exposed employees that served as the referent group. Subjects were interviewed and respiratory symptoms questionnaires, as suggested by the American Thoracic Society (ATS), were completed for them. Thereafter, they underwent chest X-ray and lung function tests. Additionally, using routine gravimetric techniques, personal dust monitoring for airborne inhalable and respirable dust was carried out at different dusty work sites. Finally to determine the chemical composition of the dust, it was analyzed by X-ray fluorescence (XRF) technique. RESULTS: XRF revealed that the major component (50.52%) of the dust was calcium magnesium carbonate, dolomite. Additionally, levels of exposure to inhalable and respirable dust were estimated to be 51.7±24.31 and 23.0±18.11mg/m3, respectively. Statistical analysis of the data showed that symptoms such as regular cough, phlegm, wheezing, productive cough and shortness of breath were significantly (p<0.05) more prevalent among exposed workers. Similarly, the ratio of FEV1/FVC in exposed subjects was significantly different from that of non-exposed individuals. In contrast, no significant abnormalities were observed in the chest radiographs of both groups. CONCLUSIONS: In conclusion, while these data cast doubt on the notion that dolomite is a harmless chemical, they provide evidence in favour of the proposition that exposure to high atmospheric concentrations of this compound is likely to be associated with respiratory symptoms.

5.
Int Arch Occup Environ Health ; 80(6): 539-46, 2007 May.
Article in English | MEDLINE | ID: mdl-17165065

ABSTRACT

OBJECTIVES: The main purpose of this study was to assess and characterize the pulmonary reactions associated with occupational exposure to talc dust. METHODS: Ninety-seven talc workers and 110 unexposed employees as the reference group were randomly selected from a local rubber industry. Standardized respiratory questionnaires were administered to the subjects, they underwent chest X-ray and were examined by a specialist for any possible respiratory abnormality to be diagnosed. Furthermore, pulmonary function tests (PFTs) were measured just before and after the work shift. Moreover, to assess the extent to which workers had been exposed to talc dust, using standard methods, inhalable and respirable dust concentrations were measured in different dusty worksites. RESULTS: The average (mean +/- SD) age (years), weight (kg), height (cm) and duration of exposure to talc dust (years) for the exposed group were 35.8 +/- 6.75, 73.1 +/- 9.2, 172.3 +/- 5.9 and 11.79 +/- 5.3, respectively. The corresponding values for the non-exposed group were 36.1 +/- 6.87, 73.36 +/- 8.1, 173.2 +/- 5.7 and 0 +/- 0, respectively. Atmospheric concentrations of inhalable and respirable talc dust were estimated to be 41.8 +/- 23.52 and 19.8 +/- 8.04 mg/m(3) (mean +/- SD), respectively. Talc exposed subjects had a significantly higher prevalence of respiratory symptoms. Similarly, PFTs revealed that exposure to this lubricating agent was associated with significant decreases in the mean percentage predicted of vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)). Likewise, there was a general tendency for VC, FVC and FEV(1) to decrease as estimated cumulative exposure (years worked) increased. Moreover, there was an acute reduction in some parameters of pulmonary function such as VC, FVC and FEV(1), over the work shift. Chest radiographs of exposed workers showed that pneumoconiosis profusions were between p 0/0 and p 2/1 according to the ILO 1980 chest X-ray classification. CONCLUSIONS: These results that are in full agreement with our preliminary observations, support the notion that occupational inhalation exposure to talc is associated with both acute and chronic respiratory disorders and induces bronchitis and interstitial lung disease.


Subject(s)
Industry , Lung Diseases/epidemiology , Rubber , Talc/adverse effects , Adult , Humans , Inhalation Exposure , Iran/epidemiology , Lung Diseases/physiopathology , Male , Occupational Exposure , Oxygen Consumption/physiology , Respiratory Function Tests , Surveys and Questionnaires
6.
Pak J Biol Sci ; 10(6): 968-71, 2007 Mar 15.
Article in English | MEDLINE | ID: mdl-19069900

ABSTRACT

Fasting during holy month, Ramadan, is a religious obligation for all adult healthy Muslims. During this month Muslims are allowed to eat and drink between sunset and dawn. However, they are not allowed to eat and drink after dawn. To assess the effects of fasting on weight, BMI (Body Mass Index) and some blood indices, we recruited 28 overweight male volunteers aged 20-26 years. They were on a balanced diet of 2000 calories, containing 70 g protein, 350 g carbohydrate and 35.5 g lipid during Ramadan, while they were on a free diet before Ramadan. Subjects were requested to drink more than 6 glasses (about 1.5 L) of water or fruit juice every night between sunset to dawn during Ramadan. Serum levels of glucose, cholesterol, triglyceride as well as weight and BMI were measured in all subjects one day before and after Ramadan. Fasting resulted in significant (p<0.05) decreases in the mean values of both, weight and the BMI. Similarly, the mean values of glucose and cholesterol were significantly decreased in subjects after Ramadan, although none of these decreases reached to a level with pathological significance. Conversely, no significant changes in serum levels of triglyceride were noted.


Subject(s)
Fasting/physiology , Islam , Overweight/physiopathology , Adult , Blood Chemical Analysis , Body Mass Index , Body Weight , Fasting/blood , Humans , Male , Overweight/blood
7.
East Mediterr Health J ; 12(3-4): 340-6, 2006.
Article in English | MEDLINE | ID: mdl-17037703

ABSTRACT

A cross-sectional study of shiftwork-related problems was carried out among health care workers at hospitals of Shiraz University of Medical Sciences, Islamic Republic of Iran. Data on personal details, shift schedule and adverse effects of shiftwork were collected from 432 randomly selected subjects by questionnaire. Sleep, social and subjective problems were more prevalent in shiftworkers than day workers. Irregular shiftwork schedules caused more social and subjective problems, as well as work dissatisfaction. Voluntary selection of shiftworking produced fewer health problems.


Subject(s)
Attitude of Health Personnel , Occupational Diseases/psychology , Personnel, Hospital/psychology , Sleep Disorders, Circadian Rhythm/psychology , Work Schedule Tolerance/psychology , Academic Medical Centers , Adult , Anxiety/etiology , Cross-Sectional Studies , Depression/etiology , Fatigue/etiology , Female , Health Services Needs and Demand , Health Surveys , Humans , Iran/epidemiology , Male , Middle Aged , Night Care/psychology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Occupational Health , Personnel Staffing and Scheduling/organization & administration , Personnel, Hospital/supply & distribution , Prevalence , Quality of Life/psychology , Sleep Disorders, Circadian Rhythm/epidemiology , Sleep Disorders, Circadian Rhythm/etiology , Social Behavior , Surveys and Questionnaires , Work Schedule Tolerance/physiology , Workforce
8.
East Mediterr Health J ; 12(6): 824-33, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17333829

ABSTRACT

Data on home accidents for a 3-year period (2000-2002) were collected from health houses, health centres and hospitals involved in a home accident prevention programme in Shiraz, Islamic Republic of Iran. A total of 15 402 accidents were registered, with a mortality rate of 1.3%. Accidents were more common in women than in men (52.1% versus 47.9%) and urban than rural areas (66.3% versus 33.7%). Burns (66.5%), followed by injuries due to sharp objects (11.3%) were the most common causes. Accidents were more prevalent in children aged under 5 years, followed by 5-9 and 15-19 years of age.


Subject(s)
Accidents, Home/statistics & numerical data , Rural Health/statistics & numerical data , Urban Health/statistics & numerical data , Accidents, Home/prevention & control , Adolescent , Adult , Age Distribution , Aged , Causality , Cause of Death , Child , Child Welfare/statistics & numerical data , Child, Preschool , Female , Health Surveys , Humans , Incidence , Iran/epidemiology , Male , Middle Aged , Population Surveillance , Registries , Seasons , Sex Distribution , Surveys and Questionnaires
9.
(East. Mediterr. health j).
in English | WHO IRIS | ID: who-117159

ABSTRACT

Data on home accidents for a 3-year period [2000-2002] were collected from health houses, health centres and hospitals involved in a home accident prevention programme in Shiraz, Islamic Republic of Iran. A total of 15 402 accidents were registered, with a mortality rate of 1.3%. Accidents were more common in women than in men [52.1% versus 47.9%] and urban than rural areas [66.3% versus 33.7%]. Burns [66.5%], followed by injuries due to sharp objects [11.3%] were the most common causes. Accidents were more prevalent in children aged under 5 years, followed by 5-9 and 15-19 years of age


Subject(s)
Burns , Prevalence , Mortality , Surveys and Questionnaires , Accidents, Home
10.
(East. Mediterr. health j).
in English | WHO IRIS | ID: who-117092

ABSTRACT

A cross-sectional study of shiftwork-related problems was carried out among health care workers at hospitals of Shiraz University of Medical Sciences, Islamic Republic of Iran. Data on personal details, shift schedule and adverse effects of shiftwork were collected from 432 randomly selected subjects by questionnaire. Sleep, social and subjective problems were more prevalent in shiftworkers than day workers. Irregular shiftwork schedules caused more social and subjective problems, as well as work dissatisfaction. Voluntary selection of shiftworking produced fewer health problems


Subject(s)
Occupational Health , Sleep , Cross-Sectional Studies , Social Environment , Work , Work Schedule Tolerance
11.
J Toxicol Environ Health ; 52(3): 249-68, 1997 Oct 24.
Article in English | MEDLINE | ID: mdl-9316646

ABSTRACT

Raised concentrations of serum bile acids (SBA) following occupational exposure to a number of halogenated aliphatic hydrocarbon solvents and after in vivo exposure of experimental animals to these substances have been reported in several studies in recent years. However, the widely used nonchlorinated aromatic hydrocarbon solvent, toluene, has not been critically examined for its effect on serum bile acids. Accordingly, the effect of in vivo treatment with toluene on SBA and its direct in vitro effects on the transport of bile acids by isolated rat hepatocytes were investigated in this study. In vivo treatment with toluene (2.3 mmol/kg body weight, ip, on each of 3 consecutive days) resulted in a significant rise in the serum concentrations of total and some individual bile acids while other parameters of hepatobiliary function were unaltered. Administration of a higher dose of solvent (9.2 mmol/kg body weight, i.p.) resulted in a further increase in total SBA levels together with a significant rise in serum activities of some liver enzymes. In vitro application of noncytotoxic doses of toluene in the vapor phase to hepatocytes isolated from untreated rats resulted in a significant inhibition of the initial rate-(V0)-of uptake of cholic acid (CA). Similarly, accumulation of CA and taurocholic acid (TC) over an extended incubation time by hepatocytes exposed to toluene was significantly inhibited. Kinetic analysis revealed a noncompetitive inhibition of CA uptake as suggested by a decline in Vmax and an unaltered K(m). In contrast, the initial rate of efflux of these substates and their continuous efflux from preloaded cells were unaffected by exposure to toluene. Thus, toluene exposure inhibited the transport and accumulation of bile acids by hepatocytes in a manner largely similar to that of halogenated solvents, and this inhibition could explain the raised SBA concentrations following in vivo exposure to this solvent. These findings are consistent with and provide mechanistic data to support previous studies where increased SBA levels (in the absence of any evidence of liver injury as measured by liver enzyme tests) were reported in workers following occupational exposure to this solvent. Additionally, in full agreement with our previous investigations in which SBA levels were found to be a sensitive biological marker of exposure to halogenated aliphatic hydrocarbon solvents, the data support a similar role for SBA on exposure to toluene as well.


Subject(s)
Bile Acids and Salts/blood , Liver/drug effects , Solvents/toxicity , Toluene/toxicity , 5'-Nucleotidase/blood , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Bile Acids and Salts/metabolism , Cells, Cultured , Cholic Acids/blood , Cholic Acids/metabolism , Dose-Response Relationship, Drug , Injections, Intraperitoneal , L-Lactate Dehydrogenase/blood , Liver/enzymology , Liver/metabolism , Male , Potassium/metabolism , Rats , Rats, Sprague-Dawley , Taurocholic Acid/blood , Taurocholic Acid/metabolism , Toluene/administration & dosage
12.
Toxicology ; 120(1): 1-10, 1997 Jun 06.
Article in English | MEDLINE | ID: mdl-9160103

ABSTRACT

Occupational exposure to a mixture of two widely used aromatic hydrocarbon solvents, xylene and toluene, has been associated with a significant rise in the concentrations of serum bile acids (SBA). We have recently shown that toluene interferes with the transport of bile acids by hepatocytes and this could explain elevated SBA after occupational exposure or following in vivo administration of this compound to experimental animals. However, it is not known if xylene, like its monomethylated homologue, toluene, could interfere with the processes of bile acid transport by hepatocytes. Therefore, the present studies were undertaken to examine this possibility. Direct addition of a non-cytotoxic dose (2.5 microliters/2.8 x 10(6) cells) of xylene (in vapour phase) to hepatocytes isolated from untreated rats significantly inhibited the initial rates (determined from slope of the lines in the linear range (20-80 s)) of uptake (V0) of 10 microM cholic acid (CA) and-taurocholic acid (TC) by 37 and 48%, respectively (P < 0.05). Similarly, accumulation of these substrates by hepatocytes over an extended incubation time up to 30 min was significantly inhibited to the same extent by xylene exposure. This inhibitory effect was found to be reversible when sufficient time was allowed for the cells to recover. In contrast, the initial rates (V0) of efflux (determined from slope of the lines in the linear range (1-5 min)) of these bile acids (25 microM) and their continuous efflux (up to 30 min) from preloaded cells incubated with a similar dose of xylene were not (except for the 1 min time point) significantly different from those of controls. In conclusion, xylene interferes with the transport of bile acids by hepatocytes in a manner largely similar to that of its monomethylated homologue, toluene. These findings extend our previous observations on aliphatic and aromatic hydrocarbon solvents and provide mechanistic data at a cellular level to support a causal role for xylene (as well as toluene) in raised SBA levels of exposed individuals.


Subject(s)
Cholagogues and Choleretics/metabolism , Cholic Acids/metabolism , Liver/drug effects , Taurocholic Acid/metabolism , Xylenes/toxicity , Animals , Biological Transport , Cell Survival/drug effects , Cells, Cultured , Cholic Acid , Liver/cytology , Liver/metabolism , Male , Potassium/metabolism , Rats , Rats, Sprague-Dawley
13.
Int Arch Occup Environ Health ; 70(3): 187-94, 1997.
Article in English | MEDLINE | ID: mdl-9298401

ABSTRACT

OBJECTIVES: The objectives of this study were threefold. First, to examine the hepatic effects of occupational exposure to 1,1,2-trichloro-1,2,2-trifluoroethane (FC 113) using conventional and newer tests (serum bile acids) of hepatobiliary function. Second, to assess the effects of altered work practices that included a reduced exposure to a different halogenated solvent (trichloroethylene) on the same parameters of liver function; and finally, to gather further data to support or refute the contention that serum bile acid (SBA) levels could provide a sensitive biological marker of exposure to these solvents. DESIGN: Two groups of workers (control and exposed) in an Australian steel industry participated in the study. The exposed group (n = 5-6) comprised individuals who had either exposure to FC 113 (68.2 +/- 12.6 ppm) or trichloroethylene (8.9 +/- 3.1 ppm) during the application of these solvents in a cleaning procedure, whereas the control group (n = 7-11) was composed of non-solvent-exposed office workers in the same company. The initial investigation involved exposure to FC 113 while a follow-up study was undertaken after changes in work practices were made including replacement of FC 113 with trichloroethylene (TRI). METHODS: Standard liver function tests and individual serum bile acids (ISBA) were measured before and after exposure to solvents and simultaneously in the control subjects by enzymatic methods and high performance liquid chromatography (HPLC), respectively. RESULTS: Statistical analysis of the data showed a significant increase in the concentration of total serum bile acids (TSBA), some of the subgroups of SBA, and a few of the ISBA in workers after a period of exposure to FC 113. After TRI replaced FC 113 together with other changes in work practices to give substantial reduction in exposure to solvent, a repeat study also found elevated SBA after the cleaning procedure but to a lesser extent. No other indications of adverse liver effects, as measured by conventional parameters of hepatobiliary function, were detected. CONCLUSION: Exposure to FC 113 was clearly associated with a significant rise in SBA levels, which are sensitive indicators of liver function. This finding is consistent with, and provides further support for, our previous investigations on chlorinated aliphatic hydrocarbon solvents which showed that SBA levels are a sensitive biological marker of exposure to these solvents. Changes in work practices including replacement of FC 113 resulted in a reduced effect on SBA, consistent with lower exposures.


Subject(s)
Bile Acids and Salts/blood , Chlorofluorocarbons, Methane , Occupational Exposure , Solvents , Trichloroethylene , Adult , Chlorofluorocarbons, Ethane , Humans , Liver Function Tests , Male
14.
Chem Biol Interact ; 99(1-3): 179-92, 1996 Jan 05.
Article in English | MEDLINE | ID: mdl-8620567

ABSTRACT

In recent years chemicals including chlorinated solvents have been found to interfere with the transport of bile acids (BA) by hepatocytes, which probably accounts for the raised serum bile acids (SBA) after exposure. However, the known cholestatic agent, alpha-naphthylisothiocyanate (ANIT) has never been fully examined for its effect on these processes. Accordingly, the direct effects in vitro and the effects of in vivo treatment on bile acid transport have been investigated in this study. Direct addition of ANIT (5-100 microns) to hepatocytes isolated from untreated rats did not result in any change in uptake or efflux of taurocholic acid (TC), one of the most obviously elevated SBA in ANIT-treated rats. Additionally, accumulation of TC over an extended incubation period was not affected by ANIT. In vivo treatment with ANIT (50 mumol/kg i.p. on each of 3 consecutive days) resulted in a marked elevation of total serum bile acids (TSBA) and a slight increase in the activity of serum alkaline phosphatase (ALP) and a very mild hyperbilirubinemia, while other markers of liver injury were unaltered. In hepatocytes isolated from these rats, Km and Vmax for uptake and V0 for efflux were no different between ANIT and vehicle-treated animals. In conclusion, ANIT showed no effects on transport of BA on in vitro exposure or after treatment in vivo where SBA were clearly elevated. The lack of effects of ANIT on transport of bile acids is consistent with other postulated mechanisms of action. Furthermore, this indicates that the effects noted with solvents are not necessarily replicated by substances known to cause histopathological cholestasis.


Subject(s)
1-Naphthylisothiocyanate/pharmacology , Bile Acids and Salts/metabolism , Liver/metabolism , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Bile Acids and Salts/blood , Biological Transport/drug effects , Cell Survival/drug effects , Cholestasis/metabolism , Cholestasis/physiopathology , Kinetics , L-Lactate Dehydrogenase/blood , Male , Rats , Rats, Sprague-Dawley , Taurocholic Acid/metabolism
15.
Toxicol In Vitro ; 10(2): 173-81, 1996 Apr.
Article in English | MEDLINE | ID: mdl-20650195

ABSTRACT

In recent years workers in our laboratory have shown that several industrial chlorinated aliphatic hydrocarbon solvents interfere with the transport of bile acids by hepatocytes and this interference may account for the raised concentration of serum bile acids that has been observed after occupational exposure to solvents. There has been concern about the effects on workers of a selective solvent used in degreasing electrical equipment, 1,1,2-trichloro-1,2,2-trifluoroethane (FC 113). However, this compound has not been investigated for effects on bile acid transport. Therefore we undertook the present study to examine the direct in vitro effects of FC 113 on uptake and efflux of bile acids by isolated rat hepatocytes. FC 113, at non-cytotoxic doses after a 20-min equilibration time, showed significant (P < 0.05) inhibitory effects on the initial rate of uptake of taurocholate (TC), whereas accumulation of TC over an extended incubation time was not affected. Kinetic analysis revealed a non-competitive inhibition of TC uptake as evidenced by a decline in V(max) and an unaltered K(m). The initial rate of efflux of TC and the continuous efflux of this model substrate from preloaded cells incubated with different doses of solvent were not significantly different from those of controls. However, the highest dose of solvent inhibited the process of efflux at the early time points. The data suggest that FC 113 interferes with bile acid transport in a reversible manner similar to that of the chlorinated aliphatic hydrocarbons. It would be expected, therefore, that this solvent would cause an increase in serum bile acids in exposed workers.

16.
Toxicol In Vitro ; 10(6): 665-74, 1996 Dec.
Article in English | MEDLINE | ID: mdl-20650250

ABSTRACT

It has previously been shown that trichloroethylene (TRI) and 1,1,2-trichloro-1,2,2-tri-fluoroethane (FC 113) interfere with the transport of bile acids by isolated human and rat hepatocytes in a dose-dependent and reversible manner. This finding may explain the rise in serum bile acids (SBA) following exposure to these chemicals. However, the effect of these compounds on the transport of bile acids across the cellular membrane in the absence of confounding variables, such as interference by intracellular metabolism, binding to cytosolic proteins and intracellular conjugation, has not been investigated. Accordingly, in vitro effects of TRI and FC 113 on uptake of [(3)H]taurocholate (TC) into purified basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles were examined by a rapid filtration technique. Both TRI and FC 113 caused a dose-dependent inhibition of TC uptake into blLPM vesicles at an approximate concentration of 3 mm and 72 mum, respectively. Initial rates of TC uptake in the presence of TRI and FC 113 were significantly inhibited by 69 and 61%, respectively (P < 0.05). In contrast, these chemicals had no effect on TC uptake into cLPM vesicles. This confirms studies in intact cells where these solvents were found to inhibit the uptake of bile acids by hepatocytes rather than interfere with the process of efflux. In conclusion, and consistent with the previous findings, the data suggest that the mechanism of TRI and FC 113-induced elevation of SBA may, in part, be due to selective inhibition of bile acid transport by the parent compounds at the basolateral domain of the hepatocyte plasma membrane.

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