• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.84-84
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• 2003

Lead has long been considered as a toxic environmental pollutant, which severely damages central nervous system. Lead can cause hypo- and de-myelination, and glial cells are closely related with myelination or demyelination. Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in the remodelling of the extracellular matrix in a variety of physiological and pathological processes. MMPs also seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system. In this study, we investigated whether lead affects MMP-9 expression in rat primary glial cells. Treatment of 0.1-5 ${\mu}$M lead dose- and time-dependently increased MMP-9 expression in rat primary glial cells. The activity of MMPs was determined using zymography. Lead activated Erk(1/2) but neither of the other endogenous MAP kinases, p38 or JNK. Inhibition of Erk(1/2) activation by PD98059, a MEK inihibitor, prevented lead-induced expression of MMP-9. The results of the present study suggest that lead intoxication may adversely affect brain function at least in part by inducing MMP-9 expression through Erk(1/2) activation in primary glial cells.

• Safety and Health at Work
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• v.3 no.1
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• pp.11-16
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• 2012

Lead poisoning is one of the earliest identified and most known occupational disease. Its acute effects have been recognized from antiquity when this condition principally afflicted manual workers and slaves, actually scarcely considered by the medicine of that time. The Industrial Revolution caused an epidemic of metal intoxication, urging scientists and physician of that period to study and identify specific symptoms and organ alterations related to chronic lead poisoning. During the 20th century, the acknowledgment of occupational and environmental toxicity of lead fostered public awareness and legislation to protect health. More recently, the identification of sub-clinical effects have greatly modified the concept of lead poisoning and the approaches of medicine towards this condition. Nowadays, lead poisoning is rarely seen in developed countries, but it still represents a major environmental problem in certain areas. Consequently, it may appear as a paradigm of "occupational and environmental disease," and the history of this condition seems to parallel the historical development of modern "Occupational and Environmental Health" as a more complete medical discipline.

• Journal of Preventive Medicine and Public Health
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• v.12 no.1
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• pp.43-48
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• 1979

For the purpose of further health control, D-penicillamine was orally administered to 8 persons who were employed in lead industry and suspected lead intoxication routine industrial health examination. The does of D-penicillamine was 600 mg per day and was administered orally in every other 5 days, For the laboratory analysis 24 hours urine and 10 gm of whole blood were collected every day. The results were as follows; 1. It was found that mean urinary lead excretion per day was 446.5 g/l and 394.98 g/l, respectively during the first 5-day and the second 5-day administration with D-penicillamine. 2. Mean lead excretion per day was $130.56{\pm}66.42g/l$ after first 5-day administration and $159.28{\pm}104.44g/l$ after second 5-day administration with D-penicillamine. 3. The level of urinary lead excretion after administration increased 3 to 4 times than that before administration with D-peniciilamine. 4. Blood and urinary lead level investigated after 6 months were $44.4{\pm}10.2g/100g\;and\;72.7{\pm}29.7\;g/l$ for the eight persons.

• Korean Journal of Community Nutrition
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• v.3 no.2
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• pp.167-173
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• 1998

This study was performed to assess the lead and cadmium status of children residing in urban factory area and to see if there is a difference of lead and cadmium status between the group with normal iron status. The mean lead concentration of male hair was 9.55ppm which is significantly higher than 6.61 ppm that of female. The mean lead concentration of male urine sample was 0.04ppm, 10.3ppm and $48.14\mu{g/L}$, which is higher than 0.08ppm, 6.08ppm and $20.69\mu{g/L}$ of normal group, respectively. In a suboptimal group the proportion of children whose urinary lead is higher than normal$(35\mu{g/L)$was 87.3%, whereas 2.5% for a normal group. The mean cadmium concentration of male hair was 2.58ppm, which is higher than 2.48ppm that of a female. The mean cadmium concentration of erythrocyte, hair and urine was 0.25ppm, 2.65ppm and $38.83\mu{g/L}$, which is higher than 0.20ppm, 2.40ppm and $19.78\mu{g/L}$ of the normal group, respectively. The proportion of children whose urinary cadmium level is higher than the low limit of risk of cadmium intoxication$(40\mu{g/L)}$ was 21.4%, whereas 0% for a mormal group. Urinary lead and cadmium level showed significantly negative correlation with the RBC count, hematocrit, hemoglobin and serum ferritin, whereas they had significantly positive correlation with FEP/Hb(p<0.01). There was no correlation between the IQ and the level of lead and cadmium.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.7
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• pp.959-967
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• 2005

Lead is a ubiquitous environmental and industrial pollutant that causes a major health concerns. It is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory and humans, including hematopoietic system, kidneys, liver, and reproductive system. This study was conducted to investigate the effect of Saengshik supplementation on the lead-induced toxicity in rats. Five week old male Sprague­Dawley rats were randomly assigned to five groups for six weeks as followings: control group (CT), lead acetate treated group (PT), and lead acetate groups administered with three different dosages of Saengshik $(SI2.5-12.5\%,\;S25-25\%,\;and\;S50-50\%).$ Lead acetate (12 mg/rat) was intragastrically administered daily for 6 weeks. The results were summarized as follows; Weight gain and food efficiency ratio were significantly lower (p<0.05) in lead administered group compared with those of the control group. Also, significant lead-induced alteration in blood hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and reticulocyte distribution width (RDW) were observed. In the liver of lead-exposed animals, there was an increase in the lipid peroxidation (MDA) and the level of glutathione (GSH), but superoxiede dismutase (SOD) activity did not change. Lead-exposed animals with $25\%\;and\;50\%$ Saengshik supplementation showed marked improvements in the values of MCH, MCV, and RDW. Also, the level of HCT was significantly increased by $50\%$ Saengshik supplementation. The levels of liver MDA in $12.5\%\;and\;50\%$ Saengshik administered groups and GSH level in $50\%$ Saengshik administered group were significantly decreased compared to the lead administered group. Also, hepatic SOD activity tended to increase in the presence of Saengshik supplementation. Furthermore, the accumulation of lead in liver and kidney was reduced by presence of Saneghshik supplementation. Liver lead concentration was significantly reduced by both $25\%\;and\;50\%$ Saengshik supplementations and kidney lead concentration was significantly reduced by the $25\%$ Saengshik supplementation. These results show that Saengshik may have a protective effect against lead intoxication but the mechanism of their effects remains unclear.

• 산업보건소식
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• no.46
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• pp.3-13
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• 1987

For the purpose of investigating the effect of occupational health service in terms of environmental control and health provision of workers on the improvement of worker's health, authors analysed the data of environmental measurement and health check-up of one lead using industry who started his investment to environmental improvement from 1980. Six hundred million won was invested for environmental improvement from 1980 to 1986. This investment brought about apparent improvement of working conditions of all of the workplaces from mean concentration of lead in air over 0.15mg/$m^3$ 1981 to mean concentration of lead in air less than 0.15mg/$m^3$. Environmental control reduced mean blood lead level from 51.2 $\pm$ 11.5ug/이 in 1983 to 39.2 $\pm$ 16.0ug/dl in 1986, and delta-aminolevulinic acid concentration 3.15 $\pm$ 2.1mg/l in 1982 to 1.96 $\pm$ 1. 7mg/l in 1986, respectively. Blood ZPP levels were decreased from 76.1 $\pm$ 58.9ug/dl in 1983 to 42.23 $\pm$ 30.3ug/dl in 1986. If 150ug/dl of blood ZPP is considered as unacceptable limit of lead intoxication, more than 10 percent of workers belonged to this category in 1983, but only 0.5 of workers showed their blood ZPP level over the 150ug/dl in 1986 It was observed that no workers whose work duration were less than one year showed their blood ZPP level over 100ug/dl, but there were high percentages of lead workers with high blood ZPP (over 150 ug/dl) who were working in uncontrolled had working condition and whose work duration were less than one year.

• Journal of Nutrition and Health
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• v.36 no.2
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• pp.117-124
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• 2003

This study was designed to test the effect of Korean traditional tea materials on oxygen-free radical metabolism in lead (Pb) -administered rats. Male rats were divided into normal, Pb-control (Pb-Con) and Pb-water extract of green tea (Camellia sinensis; GT) , persimmon leaf (Diospyros kaki; PL) , safflower seed (Carhamus tinctorius: SS) , Du-Zhong (Eucommia ulmoides; EU) groups, respectively. Pb intoxication was induced by administration of lead acetate (25 mg/kg. B.W., oral) weekly. The extract was administered based on 1.26 g of raw material/kg B.W./day for 4 weeks. When the GT, PL, SS and EU were supplemented to the Pb-administered rats, hepatic lipid peroxide levels were significantly lower compared to the Pb-Con group. Hepatic cytochrom P-450 content and aminopyrine N-demethylase activity was lower in the Pb-Con group than in the normal group, whereas xanthine oxidase activity was significantly elevated in Pb-administered rats. The water extract of GT, PL, SS and EU supplementation attenuated changes in enzyme activities generating reactive oxygen species in the liver. Hepatic superoxide dismutase, catalase and glucose 6-phosphate dehydrogenase activities were significantly higher in the Pb-Con group than in the normal group, while monoamine oxidase activity also tended to increase in the Pb-administered rats. However, glutathione peroxidase and glutathione S-transferase activities, and glutathione content significantly decreased through Pb intoxication. The supplementation of GT, PL, SS and EU induced alleviation changes of hepatic antioxidant enzyme activity.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.209-214
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• 2004

Lead has long been considered as a toxic environmental pollutant that severely damages the central nervous system. In various neurogenerative diseases, actrocytes become activated by proinflammatory cytokines. In the present study, we investigated whether lead (Pb$^{2+}$) affects inducible nitric oxide synthase (iNOS) expression in activated glial cells. Rat primary glial cells were stimulated with lipopolysaccharide (LPS, 1 ${\mu}$g/ml) plus IFN$_{\gamma}$(100 U/ml). Pre-treatment of Pb$^{2+}$ increased nitric oxide (NO) production in LPS/IFN$_{\gamma}$-stimulated glial cells. Lead itself, however, suppressed the basal production of NO in control glial cells. Addition of the iNOS inhibitors L-NAME (1 mM) and L-NNA (800 ${\mu}$M) prevented the Pb$^{2+}$-induced increase in NO production. Western blot analysis showed that pre-treatment of Pb$^{2+}$ augmented LPS/IFN$_{\gamma}$-induced increase in iNOS immunoreactivity, which was well correlated with the increased NO production. In addition, pre-treatment of Pb$^{2+}$ synergistically increased the iNOS mRNA expression induced by LPS and IFN${\gamma}$. The present results indicate that lead intoxication adversely affect brain function by potentiating iNOS expression and NO production in activated glial cells observed in various neurodegenerative diseases.

• Applied Microscopy
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• v.33 no.3
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• pp.205-214
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• 2003

To investigate the effect of the squalene against the lead toxicity. A healthy male of ICR mice were used for experiment. The SOD was observed after the intraperitoneal injection in mice. The ultrastructural changes of the liver were observed after the intraperitoneal injection in mice. The experimental groups were divided into two groups. Group A was control group that squalene was not treated after intraperitoneal injection of lead acetate. Group B was squalene treatment group that squalene solution was injected after intraperitoneal injection of lead acetate. All groups were used to 10 mice. The results were as follow: SOD activity in the liver, Group A was lower than in normal. But, Group B was higher than in Group A (P<0.05). In the histological observation, Group A were showed that the inner cavity of mitochondria swellen and development of cristae weakened. Swelling of lamellae of rough endoplasmic reticulum (rER) was showed. It was concluded that the SQ will be effective for the recovery of hepatic cell at lead intoxication.