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Original Article
The Role of CYP2B6*6 Gene Polymorphisms in 3,5,6-Trichloro-2-pyridinol Levels as a Biomarker of Chlorpyrifos Toxicity Among Indonesian Farmers
Jen Fuk Liem, Dwi A. Suryandari, Safarina G. Malik, Muchtaruddin Mansyur, Dewi S. Soemarko, Aria Kekalih, Imam Subekti, Franciscus D. Suyatna, Bertha Pangaribuan
J Prev Med Public Health. 2022;55(3):280-288.   Published online May 16, 2022
DOI: https://doi.org/10.3961/jpmph.21.641
  • 3,026 View
  • 136 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary Material
Objectives
One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used.
Methods
A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants.
Results
The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/*6. TCPy concentrations were higher among participants with CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy.
Conclusions
The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.
Summary

Citations

Citations to this article as recorded by  
  • Human CYP2C19 Substrate and Inhibitor Characterization of Organophosphate Pesticides
    Patricia A. Vignaux, Pratik Shriwas, Andre Revnew, Garima Agarwal, Thomas R. Lane, Craig A. McElroy, Sean Ekins
    Chemical Research in Toxicology.2023; 36(9): 1451.     CrossRef
  • The determinants of thyroid function among vegetable farmers with primary exposure to chlorpyrifos: A cross-sectional study in Central Java, Indonesia
    Jen Fuk Liem, Imam Subekti, Muchtaruddin Mansyur, Dewi S. Soemarko, Aria Kekalih, Franciscus D. Suyatna, Dwi A. Suryandari, Safarina G. Malik, Bertha Pangaribuan
    Heliyon.2023; 9(6): e16435.     CrossRef
Review
Environmental Mercury and Its Toxic Effects
Kevin M. Rice, Ernest M. Walker, Miaozong Wu, Chris Gillette, Eric R. Blough
J Prev Med Public Health. 2014;47(2):74-83.   Published online March 31, 2014
DOI: https://doi.org/10.3961/jpmph.2014.47.2.74
  • 50,560 View
  • 1,172 Download
  • 636 Crossref
AbstractAbstract PDF

Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

Summary

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Special Article
Methylmercury Exposure and Health Effects
Young-Seoub Hong, Yu-Mi Kim, Kyung-Eun Lee
J Prev Med Public Health. 2012;45(6):353-363.   Published online November 29, 2012
DOI: https://doi.org/10.3961/jpmph.2012.45.6.353
  • 25,844 View
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AbstractAbstract PDF

Methylmercury is a hazardous substance that is of interest with regard to environmental health, as inorganic mercury circulating in the general environment is dissolved into freshwater and seawater, condensed through the food chain, ingested by humans, and consequently affects human health. Recently, there has been much interest and discussion regarding the toxicity of methylmercury, the correlation with fish and shellfish intake, and methods of long-term management of the human health effects of methylmercury. What effects chronic exposure to a low concentration of methylmercury has on human health remains controversial. Although the possibility of methylmercury poisoning the heart and blood vessel system, the reproductive system, and the immune system is continuously raised and discussed, and the carcinogenicity of methylmercury is also under discussion, a clear conclusion regarding the human health effects according to exposure level has not yet been drawn. The Joint FAO/WHO Expert Committee on Food Additives proposed to prepare additional fish and shellfish intake recommendations for consumers based on the quantified evaluation of the hazardousness of methylmercury contained in fish and shellfish, methylmercury management in the Korea has not yet caught up with this international trend. Currently, the methylmercury exposure level of Koreans is known to be very high. The starting point of methylmercury exposure management is inorganic mercury in the general environment, but food intake through methylation is the main exposure source. Along with efforts to reduce mercury in the general environment, food intake management should be undertaken to reduce the human exposure to methylmercury in Korea.

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Original Article
Acute Testis Toxicity of Bisphenol A Diglycidyl Ether in Sprague-Dawley Rats.
Yun Jung Yang, Shin Young Lee, Kyung Yong Kim, Yeon Pyo Hong
J Prev Med Public Health. 2010;43(2):131-137.
DOI: https://doi.org/10.3961/jpmph.2010.43.2.131
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AbstractAbstract PDF
OBJECTIVES
Bisphenol A diglycidyl ether (BADGE) is a liquid compound obtained by condensation of two molecules of epichlorohydrin with one molecule of bisphenol A. General and reproductive toxicity with BADGE has been reported higher than 1000 mg/kg/day. This study was performed to show the effects of acute exposure to BADGE below 1000 mg/kg/day on the testis in adult male rats. METHODS: BADGE was administered by gastric lavage in a single dose of 500, 750, 1000, and 2000 mg/kg/day in 8-week old male SPF Sprague-Dawley rats. The right testis was processed for light microscopic analysis. The left testis was homogenized and spermatids were counted to determine the daily sperm production and daily abnormal sperm production. The sperm count, sperm motility, and incidence of abnormal sperm were estimated in the epididymis. In testicular sections, the seminiferous tubules were observed for qualitative changes. The progression of spermatogenesis was arbitrarily classified as full-matured, maturing, and immature. The specimen slide was observed at 3 points and 10 seminiferous tubules were evaluated at each point. RESULTS: The male rats exposed to single oral dose of BADGE at 750, 1000, and 2000 mg/kg/day were significantly increased the number of immature and maturing sperm on the testis. There were no significant differences with respect to sperm head count, sperm motility, and sperm abnormality in the BADGE treatment groups. CONCLUSIONS: These results suggest that single oral exposure of BADGE 750 mg/kg/day can affect adult male testis development.
Summary

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Review
Adverse Drug Reaction Surveillance System in Korea.
Nam Kyong Choi, Byung Joo Park
J Prev Med Public Health. 2007;40(4):278-284.
DOI: https://doi.org/10.3961/jpmph.2007.40.4.278
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AbstractAbstract PDF
Despite extensive researches and pre-market clinical trials, only limited information on the adverse drug reactions (ADRs) of a drug can be collected at the time of market approval from regulatory agency. ADRs constitute a major public health problem. Post-marketing surveillance of drugs is important to detect signals for ADR. In Korea, one of the main methods for monitoring the safety of marketed drugs is spontaneous reporting system of suspected ADRs. Re-examination and re-evaluation system are in force for monitoring safety of new market approval drugs and currently under marketing drugs, respectively. Recently, regional pharmacovigilance centers were designated from Korean Food and Drug Administration for facilitating ADR surveillance. Over recent years, with the development of information technology, there has been an increased interest in establishing data mining system for detecting signals from Health Insurance Review Agency database. The purpose of this paper is to review the current status of Korean ADR surveillance system and suggest the possible solutions for developing active pharmacovigilance system in Korea.
Summary

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Research Support, Non-U.S. Gov't
Developmental Toxicity by Exposure to Bisphenol A Diglycidyl Ether during Gestation and Lactation Period in Sprague-dawley Male Rats.
Un jun Hyoung, Yun Jung Yang, Su Kyoung Kwon, Jae Hyoung Yoo, Soon Chul Myoung, Sae Chul Kim, Yeon Pyo Hong
J Prev Med Public Health. 2007;40(2):155-161.
DOI: https://doi.org/10.3961/jpmph.2007.40.2.155
  • 5,569 View
  • 90 Download
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AbstractAbstract PDF
OBJECTIVES
Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. METHODS: Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. RESULTS: Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. CONCLUSIONS: These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.
Summary

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Original Articles
Comparative Hepatotoxicity Assessment of Cadmium and Nickel with Isolated Perfused Rat Liver(IPRL).
Bong Suk Cha, Seung Jun Wang, Sei Jin Chang, Jung Woo Lee
Korean J Prev Med. 2000;33(1):117-124.
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AbstractAbstract PDF
OBJECTIVES
It is the objective of this study to compare hepatotoxicity of nickel chloride and cadmium chloride with each other through IPRL(Isolated Perfused Rat Liver) method. METHODS: Biochemical indicator of hepatic function such as AST(aspartate aminotransferase), ALT(alanine aminotransferase), LDH(lactate dehydrogenase) and perfusion flow rate were used as the indicator of hepatotoxicity. Oxygen consumption rate were used as viability indicator. 300(+/-50) g - weighted rats were allocated randomly to each group(0 micrometer, 50 micrometer, 200 micrometer NiCl2 and CdCl2 exposure) by 5, totally 25. After Krebs-Ringer bicarbonate buffer solution flowed into the portal vein and passed the liver cell, it flowed out of vena cava. Liver was administered with each NiCl2 and CdCl2 of each concentration and observed with buffer solution sampling time. Buffer which got out of liver was sampled and then biochemical indicator of hepatotoxicity was measured. RESULTS: AST, ALT, and LDH in buffer increased with sampling time much more in CdCl2 exposure group than NiCl2 exposure group in both 50 and 200 micrometer and statistical significance was verified with 2-way repeated ANOVA. Viability was decreased more and more in all substances during passed time. CONCLUSIONS: It is inferred that CdCl2 has stronger hepatotoxicity than NiCl2. IPRL method would be used widely for acute hepatotoxicity when considerating the benefit of it.
Summary
In Vitro Magnetometric Evaluation for Toxicity to Alverolar Macrophage of Arsenic Compounds.
Young Chae Cho
Korean J Prev Med. 1999;32(4):467-472.
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AbstractAbstract PDF
OBJECTIVES
This study was conducted to evaluate the cytotoxicity of gallium arsenide(GaAs), indium phosphide(InP) and indium arsenide(InAs) all of which are used as the semiconductor eletments in semiconductor industry. METHODS: Cytotoxicity in the alveolar macrophage was evaluated by the measurement of in vitro magnetometry, LDH release assay and histological examination. RESULTS: The relaxation curves by the in vitro magnetometry showed that GaAs has the cytotoxicity for the alveolar macrophage which is more significant in the higher dosages, while this cytotoxicity is not appeared in the groups added with InP or InAs or PBS. In the decay constant for two minutes after magnetization, GaAs-added groups showed a significant decrease with increasing doses, but both InP- and InAs-added groups did not show any significance. The LDH release assay showed a dose-dependent increasing tendency in the GaAs-, InP- and InAs-added groups. In terms of cellular morphological changes, GaAs-added groups revealed such severe cellular damages as prominent destructions in cell membranes and their morphological changes of nucleus, while InP- and InAs-added groups remained intact in intracellular structures, except for cytoplasmic degenerations. CONCLUSIONS: It is suggested that GaAs is more influential to cytotoxicity of alveolar macrophages than InP and InAs.
Summary
Nitric Oxide-Mediated Cytotoxicity of Manganese in Basal Ganglia Neuronal Cells.
Dong Hoon Shin, Yong Wook Jung, Jae Hoon Bae, Dae Kyu Song, Won Kyun Park, Bok Hyun Ko, Doo Hie Kim
Korean J Prev Med. 1999;32(4):459-466.
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AbstractAbstract PDF
OBJECTIVES
We have investigated to manifest whether manganese-induced neurotoxicity is mediated by nitric oxide(NO) in the rat primary neuronal cultures and assess the effect of Mn2+ on the N-methyl-D aspartate(NMDA) receptors. METHODS: We have used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay to examine the effect of cytotoxicity of MnCl2 in neuronal cells . NO production was determined by measuring nirites, a stable oxidation product of NO. The neurons in the rat that contains neuronal nitric oxide synthase(nNOS) were examined by immunofluorescence and confocal microscopy. The effects of Mn2+ on the NMDA receptors was assesed by the whole cell voltage clamp technique. RESULTS: We showed that the NO release and NOS expression were increased with 500uM MnCl2 treatment and an NOS inhibitors, NG-nitro-L-arginine , prevented neurotoxicity elicited by manganese. In the electrophysiological study, Mn2+ does not block or activate the NMDA receptors and not pass through the NMDA receptors in a neurons of basal ganglia. CONCLUSIONS: It is concluded that manganese neurotoxicity in basal ganglia was partially mediated by nitric oxide in the cell culture model.
Summary
Study on the Exposure Levels of Organic Solvents and Subjective Symptoms of Dry-cleaning Workers.
Soo Young Kim, Jeong Yun Kim, Yeon Kyeng Lee, Sok Goo Lee, Young Soo Lee, Young Chae Cho, Tae Young Lee, Dong Bae Lee
Korean J Prev Med. 1998;31(4):628-643.
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AbstractAbstract PDF
To investigate the exposure levels of organic solvents and subjective symptoms of dry-cleaning workers, 77 male and 52 female dry-cleaning workers who had been worked in a small city of Chungnam province, and a large city, Taejon were selected for the study group. Air concentrations of organic solvents in the working environment were analyzed, and subjective symptoms of dry-cleaning workers were surveyed, from July to August 1996. The results obtained were as follows: 1. The concentrations of organic solvents in the working environment were within permissible TLV-TWA limits. 2. For the 13 symptom clusters, the most frequently complained symptom clusters were fatigue as 71.3%, and followed by depression and urinary disturbances as 53.5% and 51.9%. Other symptom clusters complained were below 50%. 3. Positive response rates of subjective symptoms were significantly higher in worker groups such as lived in a large city, female, higher education level, more frequently alcohol drinking, higher concentration of organic solvent in working environment, work in alone. 4. Workers who had used solvent B showed 2.3 point higher scores of subjective symptoms than those of solvent A. Of the subjective symptoms scores, amnesia and nervousness were higher in solvent B user group than solvent B user group. 5. As a result of factor analysis, 3 factors such as depression, urinary disturbance and neurologic disturbance were selected. 6. As a result of the logistic regression analysis, sex, the number of fellow workers, working time, region, job tenure, smoking, alcohol drinking, ventilating system, concentration of organic solvent in working environment and place of residence were selected for the related variables For the conclusion, even though the concentrations of organic solvents in the working environments of dry-cleaning workers were within permissible limit of TLV-TWA, many dry-cleaning workers complained symptoms, such as fatigue, depression, urinary disturbances and so on. And the factors affecting to the symptoms of dry-cleaning workers were the number of fellow workers, work hours, region, job tenure, smoking and alcohol drinking.
Summary
In Vitro Assessment of Cytotoxicity and Mutagenicity of Rock Wool Fibers.
Yun Chul Hong, Kwan Hee Lee
Korean J Prev Med. 1997;30(3):555-566.
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AbstractAbstract PDF
This study was carried out to evaluate the cytotoxicity of rock wool fibers(RWFs) such as cell division disturbance, chromosomal and DNA damage, and mutagenicity using cultured cells. RWFs were the man made mineral fibers. In order to find the correlation between the cytotoxicity of RWFs and the phagocytic capacity of cells, the phagocytic processes were observed using scanning electron microscope. Cell division disturbance by RWFs was evaluated by the formation of multinucleated giant cells. The chromosomal damage was evaluated by the micronucleus formation. For the evaluation of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) formation was measured utilizing calf thymus DNA. Mutagenicity was determined by the point mutation of HGPRT and the effect of RWFs on cell transformation was also observed. 1. Compared with the results of chrysotile, RWFs were no or little effect on the cell growth according to the results done by the tests of cell proliferation inhibition and relative plating efficiency. 2. The frequency of multinucleated giant cell formation was increased by the treatment of RWFs and it was dose-dependent. However, the effect of RWFs was weaker than that of chrysotile. 3. The number of micronuclei formed in the RWFs treated cells was between those of cells treated with chrysotile and those of untreated cells. 4. The 2 fold increase in the formation of 8-OH-dG in calf thymus DNA was observed in the cells treated with RWFs in the presence of H2O2. On the other hand, chrysotile had no effect on the 8-OH-dG formation. 5. RWFs had no effect on the HGPRT point mutation and cell transformation. These results showed that RWFs could induce chromosomal damage, cell division disturbance and oxidative DNA damage in the RWFs treated cells.
Summary
Phototoxic Dermatosis among Coal-tar Pitch Workers.
Cheol Jung, Hyun Sul Lim, Doo Hie Kim, Yeol Oh Sung
Korean J Prev Med. 1997;30(1):145-156.
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AbstractAbstract PDF
Interview survey and dermatological examination have been performed to investigate the health problems of workers continuously exposed to coal-tar pitch. The phototoxicity of coal-tar pitch was confirmed by the photopatch tests for six healthy adults. The main results are followings; 1. There was no special history of allergic diseases in both the exposed and non-exposed group. 2. The frequency of the phototoxic dermatosis and the coal-tar acne in the exposed group was significantly greater(p<0.05) than that of the control group. In the exposed group, the phototoxic dermatosis and the coal-tar acne were observed in nine workers(90%) and seven workers(70%), respectively. However, those disease were not observed in the control group. 3. Five results(83%) were positive to the photopatch test for coal-tar pitch 48 hours after UVA irradiation. But the lesion was subsiding 72 hours after UVA irradiation. 4. Malignant cancers were not reported among workers ever exposed to coal-tar pitch. In conclusion, it appears that workers exposed to coal-tar pitch have high risks of phototoxic dermatosis and coal-tar acne. A health policy should be provided to prevent phototoxic dermatosis among coal-tar pitch workers. More studies are required to determine malignancy.
Summary
An experimental study on the effect of maltol against oxygen toxicity.
Sung Joo Hwang, Soo Hon Cho, Dork Ro Yon
Korean J Prev Med. 1993;26(4):551-564.
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AbstractAbstract PDF
Since the widespread application of hyperbaric oxygenation in clinical medicine, the problems of oxygen toxicity have been attracting a deep interest from the researchers on hyperbaric medicine as a practical issue. Among extensive research trials, the study on the protective agents oxygen toxicity occupied one of the most challenging field. As the mechanisms of oxygen toxicity, the role of the oxygen free radicals produced by peroxidation process are strongly accepted by the leading researchers on oxygen toxicity, the probable protective effects of antioxidant against oxygen toxicity are sustaining a sufficient rational. Maltol(2-methyl-3-hydroxy-gamma-pyrone) which is known to be a component of Korean red ginseng has been reporting to have an antioxidant action. But, further study is needed to provide definite evidence for this compound to be an antioxidant, since the action was based on the results which were obtained under in vitro experiment. In this study, the author attempted to evaluate the effect of maltol as protective agent against oxygen toxicity through the observation of death rate, convulsion rate, time to convulsion and microscopic pathological changes in some organs of experimental rats exposed to various conditions. The findings observed are as follows: 1) The death rate, convulsion rate, time to convulsion, lung/weight ratio and microscopic pathological finding of lung were identified as reliable objective and quantitative indices for oxygen toxicity. 2) Maltol showed excellent protective effect against pulmonary oxygen toxicity as an antioxidant.
Summary
A Study on The Effect of Hyperoxia on EKG Findings of Rabbits.
Soo Jin Lee, Jae Cheol Song, Hung Bae Park
Korean J Prev Med. 1992;25(1):34-43.
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AbstractAbstract PDF
To investigate the effect of hyperoxia on EKG findings and to evaluate the applicability of EKG as noninvasive monitoring index of oxygen toxicity, 38 rabbits were continuously exposed to 6 different conditions-3 hyperbaric oxygenations (HBO-2.5, 3.5 and 5ATA, 100% O2), normobaric oxygenation (NBO, 100% O2), hyperbaric aeration (HBA-5ATA, 21% O2) and normobaric aeration (NBA, 21% O2)-for 120 minutes and their EKG and time to dyspnea and convulsion were recorded. Dyspnea and death were observed in exposure conditions of HBO-3.5 and HBO-5 (Positive rate of dyspnea; 10%, 100%, death; 10%, 25%, respectively) only, and convulsion in 4 oxygenation groups (NBO; 20%, HBO-2.5; 20%, HBO-3.5; 20%, HBO-5; 88%). Abnormal EKG findings included arrhythmia and ST-T changes and the incidences was increasing with doses(partial pressure of oxygen). In addition to EKG change, findings observed during exosure were dyspnea and convulsion in the order of appearence and when non specific ST-T change was accepted as positive (abnormal) finding, the frequency of abnormal EKG was statistically significant(p<0.01), but when it was excluded from positive results, the frequency of EKG change was not significant(p>0.05). These results suggest that the effect of hyperoxia on heart is myocardial ischemia and arrhythmia, that oxygenation more than 3.5ATA causes myocardial damage in 120 minutes exposure, and that EKG is valuable as monitoring index of oxygen toxicity.
Summary
Interaction of Sodium Selenite on Neurotoxicity Induced by Methylmercuric Chloride.
J S Park, H M Lee, Y Chung, D C Shin, J H Roh, Y H Moon
Korean J Prev Med. 1992;25(1):13-25.
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AbstractAbstract PDF
This study was conducted to investigate the mechanism of protective effect by sodium selenite in Methylmercuric chloride neurotoxicity, increasing intracellular Ca2+ concentration of the neuron. Methylmercuric chloride of 3 mg/kg of body weight was administered simultaneously with sodium selenite of 5 mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride(25 micrometer, 50 micrometer, 100 micrometer) and sodirum selenite(200 micrometer) on free intrasynaptosomal Ca2+ concentration were studied using the fluorescent Ca2+ indicator fura2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succinic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular Ca2+ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal Ca2+ concentration were measured with fura2 in vitro.The results were summarized as follows; 1. The combined administration of CH3HgCl and Na2SeO3 and pretreatment of Na2SeO3 according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of CH3HgCl only. 2. The combined administration of CH3HgCl and Na2SeO3 and pretreatment of Na2SeO3 increased more succinic dehydrogense and acetylcholinesterase activities compared to the administration of CH3HgCl only. Particularly pretreatment of Na2SeO3 significantly more compared to the administration of CH3HgCl only. The concentration of adenosine-5'-triphosphate in Na2SeO3 treatment groups revealed a favourable effect compared to the administration of CH3HgCl only. 3. Intracellular Ca2+ concentration in administration of CH3HgCl only was increased significantly more than control group in all test hours but was increased significantly more at 48 hous only after treatment in combined administration of CH3HgCl and Na2SeO3 and pretreatment of Na2SeO3 according to time interval more decreased significantly intracellular Ca2+ concentration compared to the administration of CH3HgCl only. 4. Free intrasynaptosomal Ca2+ concentration in the combined administration of CH3HgCl and Na2SeO3 was decreased (24%-40%) significantly more than the administration of CH3HgCl only. From the above results, the specific dosage of Na2SeO3 decreased increment of intracellular Ca2+ concentration induced by administration of CH3HgCl. These findings suggest the protective mechanism of Na2SeO3 on the neurotoxicity of CH3HgCl.
Summary

JPMPH : Journal of Preventive Medicine and Public Health