In this study, we analyzed polychlorinated biphenyls (PCBs) in the blood of Yusho patients collected from medical check-ups, which were conducted in 2012. The results show that 65 PCB isomers, not including non-ortho PCBs, were detected in the blood samples, and the total concentration was 620 ng g(-1) lipid. This value was comparable to the concentration in blood samples collected in 2005, and indicated that PCB concentrations in Yusho patients remained unchanged from 2005 to 2012. Here, we focused on major and specific PCB isomers in the blood samples of Yusho patients and normal controls. Examples of the former include hexaCB-153, hexaCB-138, and heptaCB-180, which are detected in human blood, while the latter include hexaCB-156, hexaCB-157, and heptaCB-189, and are highly detected in the blood of Yusho patients. Additionally, we tried to determine why the specific isomers were highly accumulated in the blood of Yusho patients as compared to the normal controls. We therefore analyzed these isomers in the contaminated rice oil, and found that the concentrations of hexaCB-156, hexaCB-157, and heptaCB-189 were 1800, 450, and 190 ng g(-1), respectively. Notably, previous studies indicated that these isomers might not be easily metabolized in humans. Therefore, these findings demonstrated that these isomers were highly accumulated in the blood of Yusho patients.
在本研究中,我们分析了2012年进行体检的玉树患者血液中的多氯联苯(PCBs)。结果表明,血样中检出65种多氯联苯异构体,总浓度为620 ng g(-1)脂质。该值与2005年采集的血液样本中的浓度相当,表明2005年至2012年玉树患者的多氯联苯浓度保持不变。在这里,我们重点研究了玉树患者和正常人血液样本中的主要和特定的多氯联苯异构体。前者包括hexaCB-153、hexaCB-138和heptaCB-180,在人类血液中检测到,后者包括hexaCB-156、hexaCB-157和heptaCB-189,在禹州患者血液中检测到的量很高。此外,我们试图确定为什么与正常对照相比,特定的异构体在玉树患者的血液中高度积累。因此,我们在污染的米油中分析了这些异构体,发现hexaCB-156、hexaCB-157和heptaCB-189的浓度分别为1800、450和190 ng g(-1)。值得注意的是,先前的研究表明,这些异构体可能不容易在人体内代谢。因此,这些发现表明这些异构体在玉树患者的血液中高度积累。
{"title":"A Study on Polychlorinated Biphenyls Specifically--Accumulated in Blood of Yusho Patients Collected from Medical Check-Ups in 2012.","authors":"Takashi Miyawaki, Shusaku Hirakawa, Takashi Todaka, Hironori Hirakawa, Tsuguhide Hori, Junboku Kajiwara, Teruaki Hirata, Hiroshi Uchi, Masutaka Furue","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this study, we analyzed polychlorinated biphenyls (PCBs) in the blood of Yusho patients collected from medical check-ups, which were conducted in 2012. The results show that 65 PCB isomers, not including non-ortho PCBs, were detected in the blood samples, and the total concentration was 620 ng g(-1) lipid. This value was comparable to the concentration in blood samples collected in 2005, and indicated that PCB concentrations in Yusho patients remained unchanged from 2005 to 2012. Here, we focused on major and specific PCB isomers in the blood samples of Yusho patients and normal controls. Examples of the former include hexaCB-153, hexaCB-138, and heptaCB-180, which are detected in human blood, while the latter include hexaCB-156, hexaCB-157, and heptaCB-189, and are highly detected in the blood of Yusho patients. Additionally, we tried to determine why the specific isomers were highly accumulated in the blood of Yusho patients as compared to the normal controls. We therefore analyzed these isomers in the contaminated rice oil, and found that the concentrations of hexaCB-156, hexaCB-157, and heptaCB-189 were 1800, 450, and 190 ng g(-1), respectively. Notably, previous studies indicated that these isomers might not be easily metabolized in humans. Therefore, these findings demonstrated that these isomers were highly accumulated in the blood of Yusho patients.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"160-8"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33881852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Foreword. The Twenty-five Reports of the Study on Yusho--PCBs and Dioxin-Related Compounds.","authors":"Masutaka Furue","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"83-4"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33880928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yusho disease was first reported in October 1968 in western Japan. Although a previous survey revealed that Yusho patients have suffered from various symptoms for 40 years after the outbreak of Yusho, some symptoms could be caused by aging. Therefore, we compared the prevalence of symptoms and medical histories (symptoms or patient-reported diseases) between Yusho patients and healthy controls to demonstrate the effects of Yusho on health conditions. We conducted a survey of healthy controls who had already registered to a survey company and created a dataset of symptoms and medical histories. We then merged the healthy control data with the Yusho survey data obtained from The Ministry of Health, Labour, and Welfare of Japan. Statistical analyses were performed using a chi-square analysis for the incidence of symptoms. Symptoms included in the major diagnostic criteria for Yusho, such as pigmentation and acneform eruption, were expectedly higher in the Yusho patients than in the healthy individuals. Symptoms that could be caused by aging, such as general fatigue, arthralgia, and numbness in the extremities, were also significantly higher in the Yusho patients after adjustment for age, indicating the possibility that Yusho may cause various systemic symptoms and diseases.
{"title":"[Comparison of the prevalence of symptoms and medical histories between Yusho patients and healthy controls].","authors":"Manabu Akahane, Shinya Matsumoto, Yoshiyuki Kanagawa, Chikage Mitoma, Hiroshi Uchi, Takesumi Yoshimura, Masutaka Furue, Tomoaki Imamura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Yusho disease was first reported in October 1968 in western Japan. Although a previous survey revealed that Yusho patients have suffered from various symptoms for 40 years after the outbreak of Yusho, some symptoms could be caused by aging. Therefore, we compared the prevalence of symptoms and medical histories (symptoms or patient-reported diseases) between Yusho patients and healthy controls to demonstrate the effects of Yusho on health conditions. We conducted a survey of healthy controls who had already registered to a survey company and created a dataset of symptoms and medical histories. We then merged the healthy control data with the Yusho survey data obtained from The Ministry of Health, Labour, and Welfare of Japan. Statistical analyses were performed using a chi-square analysis for the incidence of symptoms. Symptoms included in the major diagnostic criteria for Yusho, such as pigmentation and acneform eruption, were expectedly higher in the Yusho patients than in the healthy individuals. Symptoms that could be caused by aging, such as general fatigue, arthralgia, and numbness in the extremities, were also significantly higher in the Yusho patients after adjustment for age, indicating the possibility that Yusho may cause various systemic symptoms and diseases.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"85-118"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33880929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dioxin and dioxin-like compounds receptor (Ahr) mainly expressed on the surface of regulatory T (Treg) cell and Th17 cell could regulate immunological functions in the Yusho patients. We prospectively analyzed data obtained in a total of 56 cases of Yusho, which include patients identified ('Nintei' ) or non-identified ( 'Minintei') or identified as a family member, at the annual health check in 2014. The number of Treg cell showed lower among identified patients compared with non-identified group or family identified group (p = 0.4184 and p = 0.291, respectively). There was also a strong correlation between serum levels of neutral fat and the number of Treg cells (p = 0.0313). These results suggest that Treg cell plays a principal role in the immune response among Yusho patients.
{"title":"[Serum Levels of Regulatory T Cell in the Yusho Patients].","authors":"Yoshiko Mine, Yutaka Kuwatsuka, Atsushi Utani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dioxin and dioxin-like compounds receptor (Ahr) mainly expressed on the surface of regulatory T (Treg) cell and Th17 cell could regulate immunological functions in the Yusho patients. We prospectively analyzed data obtained in a total of 56 cases of Yusho, which include patients identified ('Nintei' ) or non-identified ( 'Minintei') or identified as a family member, at the annual health check in 2014. The number of Treg cell showed lower among identified patients compared with non-identified group or family identified group (p = 0.4184 and p = 0.291, respectively). There was also a strong correlation between serum levels of neutral fat and the number of Treg cells (p = 0.0313). These results suggest that Treg cell plays a principal role in the immune response among Yusho patients.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"124-6"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33880931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yusho incident is an unprecedented mass food poisoning that occurred in the western area of Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations in company with systemic, ophthalmological, and mucosal symptoms for a long period. Since the outbreak of Yusho, the Study Group of Yusho has been conducting annual medical check-ups on Yusho victims. We describe here the latest research findings of chronic dioxin-induced toxicity to Yusho patients and the mechanisms of toxicities of dioxins through the aryl hydrocarbon receptor (AhR) pathway. High amounts of PCBs and PCDFs are still present in a number of patients with Yusho. The patients have persistent various symptoms, some of which were significantly associated with blood levels of PCBs, dioxins, or dioxin-like compounds. The adverse effects on the next generation are also found. According to the findings of recent basic studies, the biological and toxicological effects mediated by the AhR system have been becoming clear; therefore, the therapeutic interventions may be found in the near future.
{"title":"[Latest Findings of Yusho and Its Therapeutic Development].","authors":"Chikage Mitoma, Hiroshi Uchi, Gaku Tsuji, Saori Koga, Masutaka Furue","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Yusho incident is an unprecedented mass food poisoning that occurred in the western area of Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations in company with systemic, ophthalmological, and mucosal symptoms for a long period. Since the outbreak of Yusho, the Study Group of Yusho has been conducting annual medical check-ups on Yusho victims. We describe here the latest research findings of chronic dioxin-induced toxicity to Yusho patients and the mechanisms of toxicities of dioxins through the aryl hydrocarbon receptor (AhR) pathway. High amounts of PCBs and PCDFs are still present in a number of patients with Yusho. The patients have persistent various symptoms, some of which were significantly associated with blood levels of PCBs, dioxins, or dioxin-like compounds. The adverse effects on the next generation are also found. According to the findings of recent basic studies, the biological and toxicological effects mediated by the AhR system have been becoming clear; therefore, the therapeutic interventions may be found in the near future.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"184-94"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33881855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate chronic immune effects of polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF), anti-SSA/Ro and anti-SSB/La antibodies were studied in serum of 213 patients with Yusho and 63 control subjects in 2013. Anti-SSA/Ro antibodies were found in 4.2% (9/213) of patients with Yusho and 1.6% (1/63) of control subjects. The prevalence rates of anti-SSA/Ro antibodies in Yusho patients were not associated with blood PCB concentration or blood 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) concentration. Anti-SSB/La antibodies were found in 1.4% (3/213) of patients of Yusho, but none of controls. Furthermore, high concentrations of PCB and 2,3,4,7,8-PeCDF were present in Yusho patients with anti-SSB/La antibodies. We conclude that anti-SSB/La antibody is present in patients with Yusho, and it may be associated with PCB and 2,3,4,7,8-PeCDF in the blood.
{"title":"[Anti- SSA/Ro and Anti-SSB/ La Antibodies in Patients with Yusho].","authors":"Hiroshi Tsuji","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To investigate chronic immune effects of polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF), anti-SSA/Ro and anti-SSB/La antibodies were studied in serum of 213 patients with Yusho and 63 control subjects in 2013. Anti-SSA/Ro antibodies were found in 4.2% (9/213) of patients with Yusho and 1.6% (1/63) of control subjects. The prevalence rates of anti-SSA/Ro antibodies in Yusho patients were not associated with blood PCB concentration or blood 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) concentration. Anti-SSB/La antibodies were found in 1.4% (3/213) of patients of Yusho, but none of controls. Furthermore, high concentrations of PCB and 2,3,4,7,8-PeCDF were present in Yusho patients with anti-SSB/La antibodies. We conclude that anti-SSB/La antibody is present in patients with Yusho, and it may be associated with PCB and 2,3,4,7,8-PeCDF in the blood.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"119-23"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33880930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but also polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. We previously measured dioxins concentrations in the blood of 854 Yusho patients by annual medical examination from 2001 to 2013. We determined the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than double those of normal controls. In 2012, a new Yusho criteria was established. Family members living with a Yusho patient were also certified as Yusho patients and called Yusho family cohabitant patients. In this study, we compared the distribution of 2,3,4,7,8-PeCDF concentration in the blood of Yusho patients and Yusho family cohabitant patients. It was suspected that the distribution of 2,3,4,7,8-PeCDF concentration in Yusho family cohabitant patients would be lower than that of Yusho patients.
{"title":"[The Distribution of Dioxin Concentrations in the Blood of Yusho Patients].","authors":"Jumboku Kajiwara, Takashi Todaka, Hironori Hirakawa, Tsuguhide Hori, Teruaki Hirata, Takao Iida, Hiroshi Uchi, Masutaka Furue","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but also polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. We previously measured dioxins concentrations in the blood of 854 Yusho patients by annual medical examination from 2001 to 2013. We determined the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than double those of normal controls. In 2012, a new Yusho criteria was established. Family members living with a Yusho patient were also certified as Yusho patients and called Yusho family cohabitant patients. In this study, we compared the distribution of 2,3,4,7,8-PeCDF concentration in the blood of Yusho patients and Yusho family cohabitant patients. It was suspected that the distribution of 2,3,4,7,8-PeCDF concentration in Yusho family cohabitant patients would be lower than that of Yusho patients.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"149-53"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33881850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We measured PCBs of blood of 154 people in the Yusho medical check-up from January 2011 through December 2014 and analyzed their PCB blood patterns. Eleven examinees were newly certified as Yusho patients during these 4 years. Of these 11, we identified three Yusho patients with the A pattern, five with the B pattern, and three with the BC pattern. We found no Yusho patients with the C pattern. The B pattern was found in 27 of the 154 examinees, such that the probability that an examinee with the B pattern would be certified as a Yusho patient was about 20%. Since 2012, any family members living with a Yusho patient have also been certified as Yusho patients. The number of such family cohabitants was 16, among whom the PCB pattern was uniformly the C pattern. There were 20 examinees born after 1989, and all those examinees were Yusho-suspected persons. The total PCB concentrations of this younger-age group was less than 0.5 ng/g on average and was low compared with the normal controls.
{"title":"[Blood PCB Concentrations and their Tendencies Examined in Fukuoka 2011-2014 Annual Inspections for Yusho].","authors":"Daisuke Yasutake, Toshitaka Kogiso, Tsuguhide Hori, Takashi Miyawaki, Takamitsu Yamamoto, Jumboku Kajiwara, Teruaki Hirata, Hiroshi Uchi, Masutaka Furue","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We measured PCBs of blood of 154 people in the Yusho medical check-up from January 2011 through December 2014 and analyzed their PCB blood patterns. Eleven examinees were newly certified as Yusho patients during these 4 years. Of these 11, we identified three Yusho patients with the A pattern, five with the B pattern, and three with the BC pattern. We found no Yusho patients with the C pattern. The B pattern was found in 27 of the 154 examinees, such that the probability that an examinee with the B pattern would be certified as a Yusho patient was about 20%. Since 2012, any family members living with a Yusho patient have also been certified as Yusho patients. The number of such family cohabitants was 16, among whom the PCB pattern was uniformly the C pattern. There were 20 examinees born after 1989, and all those examinees were Yusho-suspected persons. The total PCB concentrations of this younger-age group was less than 0.5 ng/g on average and was low compared with the normal controls.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"154-9"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33881851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maternal exposure to dioxins causes a number of developmental disorders in the offspring. Previous studies have suggested that lactational exposure to 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) reduces the pup level of thyroid hormone after weaning, leading to the damage to their development including neural maturation. However, the specificity for age and dioxin congeners as well as dose dependency in terms of a reduction in pup thyroid hormone remains to be clarified. To address this issue, we investigated whether TCDD or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), one of the dioxins which caused 'Yusho' incident, affects the status of thyroid hormone during the fetal and neonatal periods. Treating pregnant rats at gestational day (GD)15 with 1 μg/kg TCDD scarcely affected the serum concentration of thyroxine, although a significant reduction by TCDD was detected at limited endpoints [GD21 and postnatal day (PND)21]. In addition, maternal exposure to TCDD (0.05-30 μg/kg) or PenCDF (1-1,000 μg/kg) did not have any change in the serum level of thyroxine in GD20 fetuses even at the maximum dose. Neither the expression of pituitary thyroid-stimulating hormone β (TSHβ) nor hypothalamic thyrotropin-releasing hormone was sensitive to TCDD treatment. In pregnant dams, TCDD decreased the serum level of thyroxine at GD20 and 21, while the pituitary expression of TSHβ was induced. These results suggest that a single administration of dioxins to pregnant rats at GD15 have little effect on the level of thyroxine in the fetuses and infants, while a reduced level of this hormone observed in the offspring at GD21 and PND21 and pregnant dams at GD20 and 21.
{"title":"[The Effect of Maternal Exposure to Dioxins on the Level of Thyroid Hormone in Developing Pups].","authors":"Yukiko Hattori, Tomoki Takeda, Junki Taura, Hiroaki Kuroki, Yuji Ishii, Hideyuki Yamada","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Maternal exposure to dioxins causes a number of developmental disorders in the offspring. Previous studies have suggested that lactational exposure to 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) reduces the pup level of thyroid hormone after weaning, leading to the damage to their development including neural maturation. However, the specificity for age and dioxin congeners as well as dose dependency in terms of a reduction in pup thyroid hormone remains to be clarified. To address this issue, we investigated whether TCDD or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), one of the dioxins which caused 'Yusho' incident, affects the status of thyroid hormone during the fetal and neonatal periods. Treating pregnant rats at gestational day (GD)15 with 1 μg/kg TCDD scarcely affected the serum concentration of thyroxine, although a significant reduction by TCDD was detected at limited endpoints [GD21 and postnatal day (PND)21]. In addition, maternal exposure to TCDD (0.05-30 μg/kg) or PenCDF (1-1,000 μg/kg) did not have any change in the serum level of thyroxine in GD20 fetuses even at the maximum dose. Neither the expression of pituitary thyroid-stimulating hormone β (TSHβ) nor hypothalamic thyrotropin-releasing hormone was sensitive to TCDD treatment. In pregnant dams, TCDD decreased the serum level of thyroxine at GD20 and 21, while the pituitary expression of TSHβ was induced. These results suggest that a single administration of dioxins to pregnant rats at GD15 have little effect on the level of thyroxine in the fetuses and infants, while a reduced level of this hormone observed in the offspring at GD21 and PND21 and pregnant dams at GD20 and 21.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"127-34"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33880932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The in vitro metabolism of 2,2',3,4,4', 5,5'-heptachlorobiphenyl (CB180) was examined using liver microsomes of rats, guinea pigs and hamsters. Of liver microsomes from untreated animals, rats and guinea pigs produced one metabolite (M-1) with the activity of 1.2 and 18.1 pmol/hr/mg protein, respectively, but hamsters did not at all. Pretreatment of phenobarbital (PB) resulted in about 32-fold increase in rats, 4-fold increase in guinea pigs and an appearance of M-1 in hamsters (15 pmol/hr/mg protein). In addition, another metabolite (M-2) was formed only by liver microsomes of PB-treated guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed no metabolite in three animals. By comparison of the GC-MS data of the metabolites with synthesized authentic samples, M-1 and M-2 was determined to be 3'-hydroxy (OH)-CB180 and 4'-OH-2,2',3,4,5,5'-hexachlorobiphenyl (CB141), respectively. These results suggest that 3'-OH-CB180 is a major metabolite and is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animals and also guinea pigs possess much higher activity to metabolize CB180 than rats and hamsters.
{"title":"[Metabolism of 2,2',3,4,4',5,5'-Heptachlorobiphenyl (CB180) by Animal Liver Microsomes].","authors":"Chiho Ohta, Koichi Haraguchi, Yoshihisa Kato, Tetsuya Endo, Osamu Kimura, Nobuyuki Koga","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The in vitro metabolism of 2,2',3,4,4', 5,5'-heptachlorobiphenyl (CB180) was examined using liver microsomes of rats, guinea pigs and hamsters. Of liver microsomes from untreated animals, rats and guinea pigs produced one metabolite (M-1) with the activity of 1.2 and 18.1 pmol/hr/mg protein, respectively, but hamsters did not at all. Pretreatment of phenobarbital (PB) resulted in about 32-fold increase in rats, 4-fold increase in guinea pigs and an appearance of M-1 in hamsters (15 pmol/hr/mg protein). In addition, another metabolite (M-2) was formed only by liver microsomes of PB-treated guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed no metabolite in three animals. By comparison of the GC-MS data of the metabolites with synthesized authentic samples, M-1 and M-2 was determined to be 3'-hydroxy (OH)-CB180 and 4'-OH-2,2',3,4,5,5'-hexachlorobiphenyl (CB141), respectively. These results suggest that 3'-OH-CB180 is a major metabolite and is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animals and also guinea pigs possess much higher activity to metabolize CB180 than rats and hamsters.</p>","PeriodicalId":12665,"journal":{"name":"Fukuoka igaku zasshi = Hukuoka acta medica","volume":"106 5","pages":"176-83"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33881854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}