• Journal of Preventive Medicine and Public Health
• /
• 제28권4호
• /
• pp.875-884
• /
• 1995

In order to investigate the level of lead exposure of workers in litharge making industry and to evaluate how lead exposure, personal habit such as smoking and drinking affect the prevalence of lead related symptoms and other study variables, we investigate 114 workers(24 office workers and 90 lead exposed workers) in a litharge making industry. Study variables chosen were blood lead(PbB), zinc protoporphyrin in whole blood(ZPP), Hemoglobin(Hb), hematocrit (Hct), SGOT and SGPT symptom questionnaires which had 15 lead exposure related symptoms were provided to all workers and filled up by themselves and reconfirmed by physician. The results obtained were as follows; 1. The mean value of PbB, ZPP and SGOT in lead exposed group were higher than those of non-exposed group, and there were no differences of means in other study variables. 2. The smoking and drinking rate of study subjects were 65.8% and 71.0% as a whole. Smoking rates were lower in non-exposed group than exposed group, but drinking rate were not. 3. There were no differences of mean values of study variables between smoker and non-smoker in non-exposed and exposed group, but there was a difference of mean value of SGOT between drinker and lion-drinker in lead exposed group. 4. While the symptom prevalence of lead exposed group were higher in neuromuscular category than non-exposed group, those of non-exposed group were higher or same with exposed group in gastrointestinal and general symptom category. 5. The symptom prevalence of smoker were higher than non-smoker regardless of exposure. 6. The symptom prevalence of drinker were only higher in gastrointestinal symptom category than non-drinker. 7. In multiple stepwise regression analysis of lead related symptoms as dependent variable and blood lead, smoking habit, drinking habit and work duration as independent variables, drinking habit contributed to the gastrointestinal symptom category, whereas blood lead and smoking contributed to the neuromuscular symptom category. For the total symptoms work duration and smoking habit contributed significantly.

• Archives of Pharmacal Research
• /
• 제18권2호
• /
• pp.90-99
• /
• 1995

The effect of protein kinase C inhibitors, sturosporine and 1-(5-isoquinolinyl sulfonyl)-2-methyl piperazine(H7) on in vitro differentiation of erythroid progenitor cells which were isolated from spleens of mice infected with the anemia-inducing strain of Friend virus were examined. Erythropoietin-mediated differentitation of erythroid progenitor cells, as determined by the incorporation of $^{59}Fe$ into protoporphyrin, was inhibited by staurosporine and H7 in a concentration -dependent manner. Scatchard analysis of the $^3H-phorbol-12$, 13-dibutyrate binding to erythroid progenitor cells revealed that at the high affinity sites the dissociation constant was 22nM and the maximum number of $^3H-phorbol-12$, 13-dibutyrate binding to erythroid progenitor cells revealed that at the high affinity sites the dissociation constant was 22nM and the maximum number of $^3H-phorbol-12$, 13-dibutyrate binding sites per cell was approximately $3.7\times10^5$. Cytosonic protein kinase C was isolated from erthroid progenitor cells and then purified by sequential column chromatogrphy. Two isoforms of protein kinase C were found. Photoaffinity labeling of the purified protein kinase C samples with $^3H-phorbol-12$12-myristate 13-acetate followed by analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autofluorography showed radiolabeled 82-KDa pepticles. Rediolabeling of the 82-KDa peptides with $^3H-phorbol-12$myristate 13-acete was almost completely blocked by excess unlabeled phorbol 12-myristate 13-acetate was almost 12-muristate 13-acetate-promoted phosphorylation with the puyrified protein kinase C samples showed that the phosphorylation of 82-KDa peptides was increased as the concentration of phorbol 12-myristate 13-acetate was increased from $10^{-8}M{\;}to{\;}10^{-4}$M. In light of the findings that erythroid progenitor cells possessed an abundance of protein kinase C and that stauroporine and H7 inhibited erythroid differentiation, it seemed likely that protein kinase C would play a role in the erythroid progenitor cell development.

• Biomolecules & Therapeutics
• /
• 제29권6호
• /
• pp.685-696
• /
• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

• 생명과학회지
• /
• 제21권11호
• /
• pp.1625-1630
• /
• 2011

CoPP는 다양한 세포에서 HO-1의 유전자 발현과 활성을 증가시키는 강력한 유도제로 알려져 있다. HO-1는 세포 및 조직의 손상을 보호한다는 연구가 활발히 진행되고 있으나, 그 작용 기전에 대해서는 아직 잘 모르고 있다. 본 논문에서는 porphyrin 계열의 CoPP의 자극에 의해 유도되는 HO-1 유전자 발현에서 NADPH oxidase의 활성이 미치는 영향을 인간 간암세포주 HepG2에서 조사하였다. 배양 중인 HepG2 세포에서 CoPP는 HO-1의 발현을 농도의존적으로 증가시키는 것을 확인하였다. NADPH oxidase 저해제로 잘 알려져 있는 DPI를 전처리한 후 CoPP로 자극한 세포에서는 HO-1의 발현이 강력하게 억제되는 것으로 나타났다. DPI의 이런 억제 효과가 HO-1의 전사 조절인자 Nrf2의 활성에도 영향을 줄 수 있기 때문에 DPI를 전처리 한 후 CoPP 자극에 의한 Nrf2의 핵으로의 이동을 분석하였다. 그 결과, DPI는 CoPP에 의해 유도되는 Nrf2의 핵으로의 이동과 세포 내 존재하는 양을 감소시키는 것을 확인하였다. 다른 HO-1 발현 유도제로 알려져 있는 hemin에 의한 자극의 경우에도 DPI는 HepG2 세포의 HO-1의 발현을 억제하는 효과를 나타내었다. 그리고, $p47^{phox}$에 대한 siRNA를 사용하여 효과적으로 $p47^{phox}$ 유전자 발현을 knockdown 시켜서 NADPH oxidase의 활성을 억제시키는 방법을 사용하였다. 그 결과, $p47^{phox}$ silencing한 세포에 CoPP를 처리한 경우는 control siRNA를 처리한 세포와 비교할 때 HO-1 발현이 현저히 감소됨을 관찰할 수 있었다. 마지막으로, 세포 내 ROS 생성을 억제하는 GSHmee가 처리된 세포에서는 CoPP나 hemin이 Nrf2의 활성을 증가시키지 못하였고, 그 결과 HO-1의 발현을 유도하지 못하는 것을 알 수 있었는데, 이는 ROS가 CoPP나 hemin에 의한 HO-1 유전자 발현 과정에 중요한 역할을 한다는 것을 의미한다. 이를 종합해 볼 때, 인간 간암세포주 HepG2에서 CoPP나 hemin의 자극에 의한 HO-1 유전자의 발현에는 NADPH oxidase의 활성이 요구된다는 것을 알 수 있고, 그 활성은 세포 내 ROS를 생성시키는 것으로 역할을 한다고 여겨진다.

• 한국잡초학회지
• /
• 제12권2호
• /
• pp.89-101
• /
• 1992

직(直), 간접적(間接的)으로 활성산소(活性酸素)를 발생시켜 엽록소(葉綠素) 및 막파괴(膜破壞)를 일으키는 제초제(除草劑)들의 선택성기구(選擇性機構)를 명확히 하기 위해서는 제초제(除草劑)의 체내흡수(體內吸收), 이행(移行), 대사(代謝) 외(外)에 작용점(作用點)에서의 감수성(感受性), 과산화(過酸化) 능력(能力), 막(膜)의 안정성(安定性) 및 항산화(抗酸化) 능력(能力)의 차이(差異) 등(等)에 대해서도 검사(檢射)되어야 할 것이다. 본(本) 실험(實驗)에서는 대부분의 백화형(白化型) 제초제(除草劑) 처리에서 관찰되는 벼, 피 반응(反應) 차이(差異)의 일부(一部)를 이러한 관점에 기준을 두어 해석해 보고자 실험(實驗)을 수행하였다. 1. 피가 벼보다 여러 백화형(白化型) 제초제(除草劑)에 대해 민감(敏感)하였으며, 무처리(無處理)의 엽신(葉身)을 절취(切取)하여 두었을때도 노화(老化), 괴사(壞死)되는 정도가 피에서 더욱 빨라 생리적(生理的)으로 약한 특성을 보였다. 2. Oxyfluorfen 처리후의 PPIX 축적과 norflurazon 처리후의 carotene 감소율(減少率)은 벼, 피간의 선택성(選擇性)과는 상관이 없었다. 3. Lipoxygenase 활성(活性)은 피가 약 5-6배(倍)높고, 불포화지방산(不飽和脂肪酸)의 비율도 피가 벼보다 높아 과산화(過酸化)가 쉽게 일어날 수 있는 소질(素質)을 갖고 있었다. 4. Peroxidase, catalase, superoxide dismutase, glutathione reductase, ascorbic acid oxidase 등(等)의 생체중당(生體重當) 활성(活性)은 벼가 피보다 각각 3.6, 11.4, 1.5. 2.5배(倍) 더 높았다. 한편 약제처리 후 항산화(抗酸化) 효소(酵素) 유기능력(誘起能力)에 있어서는 오이 peroxidase에서와는 달리 벼, 피에서는 변화가 없거나 오히려 비슷한 정도로 활성(活性)이 떨어지는 경향이었다. 5. 항산화제(抗酸化劑) 함량(含量)의 경우 벼가 피보다 ${\alpha}$-tocopherol은 2.3배(倍) ascorbic acid는 4.1배(倍), GSH는 1.7배(倍), carotenoid는 1.8배(倍) 높았다. 따라서 유묘기(幼苗期)(3-4 엽기(葉期) 미만(未滿))의 벼, 피에 백화형(白化型) 제초제(除草劑)를 처리할 때 피가 공통적 A로 감수성(感受性)을 보였던 이유는 피가 기본적으로 가지고 있는 성질(性質) 즉 낮은 색소대사력(色素代謝力), 항산화(抗酸化) 효소(酵素)의 낮은 활성(活性), 항산화제(抗酸化劑)의 저함량(低含量), 높은 불포화(不飽和) 지방산(脂肪酸) 비율(比率), lipoxygenase의 고활성(高活性) 등(等)을 보유하고 있는데도 그 원인이 있는 것으로 생각된다.

• Journal of Preventive Medicine and Public Health
• /
• 제29권4호
• /
• pp.747-764
• /
• 1996

This study intended to obtain an useful information for health management of lead exposed workers and determine biological monitoring interval in early period of exposure by measuring the lead exposure indices and work duration in all male workers (n=433 persons) exposed less than 1 year in 6 storage battery industries and in 49 males who are not exposed to lead as control. The examined variables were blood lead concentration (PBB), Zinc-protoporphyrin concentration (ZPP), Hemoglobin (HB) and personal history; also measured lead concentration in air (PBA) in the workplace. According to the geometric mean of lead concentration in the air, the factories were grouped into three categories: A; When it is below $0.05mg/m^3$, B; When it is between 0.05 and $0.10mg/m^3$, and C; When it is above $0.10mg/m^3$. The results obtained were as follows: 1. The means of blood lead concentration (PBB), ZPP concentration and hemoglobin(HB) in all male workers exposed to lead less than 1 year in storage battery industries were $29.5{\pm}12.4{\mu}g/100ml,\;52.9{\pm}30.0{\mu}g/100ml\;and\;15.2{\pm}1.1\;gm/100ml$. 2. The means of blood lead concentration (PBB), ZPP concentration and hemoglobin(HB) in control group were $5.8{\pm}1.6{\mu}g/100ml,\;30.8{\pm}12.7{\mu}g/100ml\;and\;15.7{\pm}1.6{\mu}g/100ml$, being much lower than that of study group exposed to lead. 3. The means of blood lead concentration and ZPP concentration among group A were $21.9{\pm}7.6{\mu}g/100,\;41.4{\pm}12.6{\mu}g/100ml$ ; those of group B were $29.8{\pm}11.6{\mu}g/100,\;52.6{\pm}27.9{\mu}g/100ml$ ; those of group C were $37.2{\pm}13.5{\mu}g/100,\;66.3{\pm}40.7{\mu}g/100ml$. Significant differences were found among three factory group(P<0.01) that was classified by the geometric mean of lead concentration in the air, group A being the lowest. 4. The mean of blood lead concentration of workers who have different work duration (month) was as follows ; When the work duration was $1\sim2$ month, it was $24.1{\pm}12.4{\mu}g/100ml$, ; When the work duration was $3\sim4$ month, it was $29.2{\pm}13.4{\mu}g/100ml$ ; and it was $28.9\sim34.5{\mu}g/100ml$ for the workers who had longer work duration than other. Significant differences were found among work duration group(P<0.05). 5. The mean of ZPP concentration of workers who have different work duration (month) was as follows ; When the work duration was $1\sim2$ month, it was $40.6{\pm}18.0{\mu}g/100ml$, ; When the work duration was $3\sim4$ month, it was $53.4{\pm}38.4{\mu}g/100ml$ ; and it was $51.5\sim60.4{\mu}g/100ml$ for the workers who had longer work duration than other. Significant differences were found among work duration group(P<0.05). 6. Among total workers(433 person), 18.2% had PBB concentration higher than $40{\mu}g/100ml$ and 7.1% had ZPP concentration higher than $100{\mu}g/100ml$ ; In workers of factory group A, those were 0.9% and 0.0% ; In workers of factory group B, those were 17.1% and 6.9% ; In workers of factory group C, those were 39.4% and 15.4%. 7. The proportions of total workers(433 person) with blood lead concentration lower than $25{\mu}g/100ml$ and ZPP concentration lower than $50{\mu}g/100ml$ were 39.7% and 61.9%, respectively ; In workers of factory group A, those were 65.5% and 82.3% : In workers of factory group B, those were 36.1% and 60.2% ; In workers of factory group C, those were 19.2% and 43.3%. 8. Blood lead concentration (r=0.177, P<0.01), ZPP concentration (r=0.135, P<0.01), log ZPP (r=0.170, P<0.01) and hemoglobin (r=0.096, P<0.05) showed statistically significant correlation with work duration (month). ZPP concentration (r=0.612, P<0.01) and log ZPP (r=0.614, P<0.01) showed statistically significant correlation with blood lead concentration 9. The slopes of simple linear regression between work duration(month, independent variable) and blood lead concentration (dependent variable) in workplace with low air concentration of lead was less steeper than that of poor working condition with high geometric mean air concentration of lead. The study result indicates that new employees should be provided with biological monitoring including blood lead concentration test and education about personal hygiene and work place management within $3\sim4$ month.