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Effects of Aminotriazole on Lung Toxicity of Paraquat Intoxicated Mice (Paraquat중독에 의한 폐독성에 미치는 Aminotriazole의 영향)

  • Lee, Seung-Il;An, Gi-Wan;Chung, Choon-Hae
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.222-230
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    • 1994
  • Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

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Respiratory Failure of Acute Organophosphate Insecticide Intoxication (유기인제 중독에 의한 호흡부전)

  • Shin, Kyeong-Cheol;Lee, Kwan-Ho;Park, Hye-Jung;Shin, Chang-Jin;Lee, Choong-Ki;Chung, Jin-Hong;Lee, Hyun-Woo
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.3
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    • pp.363-371
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    • 1999
  • Background: Because of the widespread use and availability of agricultural insecticides, acute organophosphate poisoning as a suicide or an accident is becoming the most common type of poisoning and serious problem in Korea. The mortality of organophosphate poisoning varied from 10 to 86 percent. The cause of death was thought to be a combination of excessive bronchial secretion, bronchospasm, respiratory muscle paralysis and depression of respiratory center, summarily respiratory failure. We evaluated the respiratory complications in patients with acute organophosphate intoxication to determine the predisposing, factors to respiratory failure and to reduce the incidence of respiratory failure or mortality. Method: We conducted a retrospective study of 111 patients with the discharge diagnosis of organophosphate poisoning who were hospitalized at Yenugnam University Hospital during the 5 years. The diagnosis of organophosphate poisoning has based on the followings (1) a history of exposure to an organophosphate compounds. (2) the characteristic clinical signs and symptoms. (3) decrease in the cholinesterase activity in the serum. Results: Respiratory failure developed in 31(28%) of 111 patients with acute organophosphate poisoning. All cases of respiratory failure developed within 96 hours after poisoning and within 24 hours in 23 patients. The 80 patients who did not develop respiratory failure survived. In 31 patients with respiratory failure, 15(44%) patients were dead. The patients with respiratory failure had more severe poisoning, that is, the lower level of serum cholinesterase activity on arrival, the higher mean dosage of atropine administered within first 24 hours. In 16 patients with pneumonia, 14 patients developed respiratory failure. In 5 patients with cardiovascular collapse, 2 patients developed respiratory failure. There was no correlation to between age, sex, the use of pralidoxime and respiratory failure. The serum cholinesterase level in survivors at time of respiratory failure and weaning was $66.05{\pm}85.48U/L$, $441{\pm}167.49U/L$, respectively. Conclusion: All the respiratory failure complications of acute organophosphate poisoning occurred during the first 96 hours after exposure. The severity of poisoning and pneumonia were the predisposing factors to respiratory failure. Aggressive treatment and prevention of the above factors will reduce the incidence of respiratory failure.

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Effect of the Inhibition of PLA2 and PAF on the Neutrophilic Respiratory Burst and Apoptosis (호중구의 Respiratory Burst에 미치는 PLA2 및 PAF와 영향 : In vitro에서의 호중구의 산소기 생성 및 Apoptosis에 관한 연구)

  • Lee, Young-Man;Kim, Sang-Gyung;Park, Yoon-Yub
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.6
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    • pp.887-897
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    • 2000
  • Background : Since the exact pathogenesis of sepsis-induced ARDS has not been elucidated, the mechanisms of enhanced neutrophilic respiratory burst were probed in endotoxin primed neutrophils associated with the roles of phospholipase A2(PLA2), platelet activating factor(PAF) and apoptosis. Methods : In isolated fresh human neutrophils, effects of the inhibition of PLA2 and PAF on the apoptosis were examined by the method of Annexin-FITC/dual PIflow cytometry. The roles of PLA2 and PAF on the neutrophilic respiratory burst were also examined by measuring oxidant generation in cytochrome-c reduction assay. Activities of the PLA2 and lysoPAF acetyltransferase (lysoPAF AT) of the neutrophils were determined to understand the effect of endotoxin on these enzymatic activities which may be related to the neutrophilic respiratory burst and apoptosis. In addition, the role roles of PLA2 and PAF in neutrophilic adhesion to bovine endothelial cells were examined in vitro by neutrophil adhesion assay. To investigate the effect of oxidants on pulmonary surfactant, cytochemical ultrastructural microscopy was performed. To inhibit PLA2 and PAF, non-specific PLA2 inhibitor mepacrine (100 nM) and WEB 2086 (100 nM) or ketotifen fumarate (10 ${\mu}g$/ml) were used respectively in all in vitro experimental sets. WEB 2086 is PAF receptor antagonist, and ketotifen fumarate is a lyso PAF AT inhibitor. Results: The mapacrine treatment, provided and the endotoxin (ETX) treatment, resulted in increased apoptosis of neutrophils (p<0.001) while treatments of WEB 2086 and ketotifen did not. The inhibition of PLA2 and PAF decreased (p<0.001) production of oxidants from PMA-stimulated neutrophils. While endotoxin increased the PLA2 activity of neutrophils (p<0.01), mepacrine supressed (p<0.001) the activity, provided after treatment of ETX. The lyso PAF actyltransferase activity (lyso PAF AT) increased (p<0.01) after treatment of ETX. In contrast, mepacrine, WEB 2086 and ketotifen showed a tendency of decreasing the activity after treatment of ETX. The treatment of ETX incresed (p<0.001) neutrophil adhesion to endothelial cells, which was reversed by inhibition of PLA2 and PAF (p<0.01). The binding of oxidants to pu1monary surfactant was identified histologically. Conclusions : The enhanced neutrophilic respiratory burst by ETX plays a pivotal role in the pathogenesis of ARDS in terms of oxidayive oxidative stress. Increased production of oxidants from neutrophils is mediated by the activations of PLA2 and lyso PAF AT.

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The Priming Effect of IFN-$\gamma$ and Numbers of IFN-$\gamma$ Receptors in Patients with Chronic Refractory Tuberculosis (난치성 결핵 환자의 단핵구에서 IFN-$\gamma$ 활성화 효과 및 IFN-$\gamma$ 수용체의 숫적 변화에 대한 연구)

  • Lee, Jae-Cheol;Yoo, Chul-Gyu;Lee, Choon-Taek;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.304-310
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    • 1999
  • Background: IFN-$\gamma$ plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-$\gamma$ caused by a defective IFN-$\gamma$ receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-$\gamma$ in the development of chronic refractory tuberculosis. Methods: The LPS-induced TNF-$\alpha$ production with or without IFN-$\gamma$ priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-$\gamma$ receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-$\gamma$ is related to IFN-$\gamma$ receptor deficiency or not. Results: The ratio of TNF-$\alpha$ produced in response to stimulation with INF-$\gamma$ and LPS to LPS alone was $13.5{\pm}7.6$ in controls, $10.8{\pm}6.4$ in recently diagnosed tuberculosis patients and $6.7{\pm}3.9$ in chronic refractory tuberculosis patients. The priming effect of IFN-$\gamma$ significantly decreased in chronic refractory tuberculosis patients compared with that in controls(p=0.002). However, IFN-$\gamma$ receptor deficiency was detected in one of chronic refractory tuberculosis patients. Conclusion: The decrease of the priming effect of IFN-$\gamma$ may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-$\gamma$ receptor deficiency.

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Outcomes in Relation to Time of Tracheostomy in Patients with Mechanical Ventilation (기계호흡환자의 기관절개 시행 시기에 따른 결과 분석)

  • Shin, Jeong-Eun;Shin, Tae-Rim;Park, Young-Mi;Nam, Jun-Sik;Cheon, Seon-Hee;Chang, Jung-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.365-373
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    • 1999
  • Background: Despite widespread use of tracheostomy in intensive care unit, it is still controversial to define the best timing from endotracheal intubation to tracheostomy under prolonged mechanical ventilation. Early tracheostomy has an advantage of easy airway maintenance and enhanced patient mobility whereas a disadvantage in view of nosocomial infection and tracheal stenosis. However, there is a controversy about the proper timing of tracheostomy. Methods: We conducted a retrospective study of the 35 medical and 15 surgical ICU patients who had admitted to Ewha Womans University Mokdong Hospital from January 1996 to August 1998 with the observation of APACHE III score, occurrence of nosocomial infections, and clinical outcomes during 28 days from tracheostomy in terms of early (n=25) vs. late (n=25) tracheostomy. We defined the reference day of early and late tracheostomy as 7th day from intubation. Results: The number of patients were 25 each in early and late tracheostomy group. The mean age were $48{\pm}18$ years in early tracheostomy group and $63{\pm}17$ years in late tracheostomy group, showing younger in early tracheostomy group. The median duration of intubation prior to tracheostomy was 3 days and 13 days in early and late tracheostomy groups. Organs that caused primary problem were nervous system in 27 cases(54%), pulmonary 14(28%), cardiovascular 4(8%), gastrointestinal 4(8%) and genitourinary 1(2%) in the decreasing order. Prolonged ventilation was the most common reason for the purpose of tracheostomy in both groups. APACHE m scores at each time of intubation and tracheostomy were slightly higher in late tracheostomy group but not significant statistically. Day to day APACHE III scores were not different between two groups with observation upto 7th day after tracheostomy, Occurrence of nosocomial infections, weaning from mechanical ventilation, and mortality showed no significant difference between two groups with observation of 28 days from tracheostomy. The mortality was increased as the APACHE m score upto 7 days after tracheostomy increased, but there were no increment for the mortality in terms of the time of tracheostomy and the days of ventilator use before tracheostomy, Conclusion: The early tracheostomy seems to have no benefit with respect to severity of illness, nosocomial infection, duration of ventilatory support, and mortality. It suggests that the time of tracheostomy is better to be decided on clinical judgement in each case. And in near future, prospective, randomized case-control study is required to confirm these results.

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The Prognostic Value of Fibroblastic Foci Quantity in Patients with Usual Interstitial Pneumonia (UIP 환자에서 측정된 Fibroblastic Foci량이 예후에 미치는 영향)

  • Park, Sung-Woo;Lee, Young-Mok;Lee, June-Hyeuk;Kim, Ki-Up;Kim, Do-Jin;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Kim, Hyun-Jo;Youm, Wook
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.6
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    • pp.540-549
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    • 2001
  • Background : Usual interstitial pneumonia (UIP) is a progressive fibrous lung disease with occasional fatal outcomes. However, the extent and rate of progression varies markedly from one patient to another. As a result, it is difficult to determine the time of the initial treatment and assess the disease activity and course. Fibroblast foci (FF) is well known to synthesize collagen actively by their myofibroblasts component. However, the prognostic value of the FF have not been evaluated in patients with VIP. Therefore this study was undertaken to determine how the number of fibroblastic foci can reflect the disease activity and progression. Methods: Twenty patients with UIP(M : F=13 : 7), who were diagnosed by a surgical lung biopsy. The number of fibroblastic foci was analyzed in terms of its correlation with the clinical manifostations, pulmonary function test, arterial blood gas analysis, and a bronchoalveolar lavage(BAL). Results : The number of fibroblastic foci did not correlate with the various lung function tests and the other clinical parameters. Interestingly, the percentage of neutrophils in the bronchoalveolar lavage fluid did correlate with the quantity of the normalized Vv of FF(r=0.60, p<0.05). The patients were divided into 2 groups, group I and II, arbitrarily, according to the value of the normalized Vv. The clinical parameters and the PIT results were not different between the two groups. In particular, the survival rate between the two groups according to the Kaplan-Meier analysis were not different. Conclusion : A large number of FF does not imply a bad prognosis in patients with UIP.

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The Differences in Resting Pulmonary Function in Relation to the Nutritional status of Patients with Chronic Obstructive Pulmonary Disease (만성폐쇄성폐질환 환자의 영양상태에 따른 안정시 폐기능 차이)

  • Mun, Yeung-Chul;Yu, Sung-Keun;Park, Hye-Jung;Park, Jong-Won;Shin, Kyeong-Cheol;Chung, Jin-Hong;Lee, Kwan-Ho;Kim, Jung-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.6
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    • pp.570-578
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    • 2001
  • Background: With cases of chronic obstructive pulmonary disease(COPD), weight loss and low body weight have been found to correlate with increased mortality and poor prognosis. Therefore, nutritional aspects are an important part of the treatment in cases of COPD. In Korea, there is only limited data available for the changes of resting pulmonary function in relation to nutritional status. This study was carried out to investigate the differences of resting pulmonary function in relation to the nutritional status of patients with COPD. Method : 83 stable patients, with moderate to severe COPD, were clinically assessed for their nutritional status and resting pulmonary function. The patients' nutritional status was evaluated by body weight and fat-free mass (FFM), which was assessed by bioelectrical impedance analysis. According to their nutritional status, the 83 patients were divided into two groups, designated as the depleted, and non-depleted, groups. Result : Of the 83 patients, 31% were characterized by body weight loss and depletion of FFM, whereas 28% had either weight loss or depleted FFM. In the depleted group, significantly lower peak expiratory flow rate(p<0.05) and Kco(p<0.01), but significantly higher airway resistance(Raw, p<0.05) were noted. There was no difference for the non-depleted group in forced expiratory volume at one second, residual volume, inspiratory vital capacity, or total lung capacity. Maximal inspiratory pressure($P_{Imax}$) was also significantly lower in the depleted group(p<0.05). Conclusion : We conclude, from our clinical studies, that nutritional depletion is significantly associated with the change in resting pulmonary function for patients with moderate to severe COPD.

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The Differences of Anthropometric and Polysomnographic Characteristics Between the Positional and Non-positional Obstructive Sleep Apnea Syndrome (체위 의존성 및 체위 비의존성 폐쇄성 수면 무호흡증후군의 신체계측인자 및 수면구조의 차이)

  • Park, Hye-Jung;Shin, Kyeong-Cheol;Lee, Choong-Kee;Chung, Jin-Hong;Lee, Kwan-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.6
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    • pp.956-963
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    • 2000
  • Backgrounds : Obstructive sleep apnea syndrome(OSA) can divided into two groups, positional(PP) and non-positional(NPP) obstructive sleep apnea syndrome, according to the body position while sleeping. In this study, we evaluated the differences of anthropometric data and polysomnographic recordings between the two types of sleep apnea syndrome. Materials : Fifty patients with OSA were divided two groups by Cartwright's criteria. The supine respiratory disturbance index (RDI) was at least two times higher than the lateral RDI in the PP group, and the supine RDI was less than twice the lateral RDI in the NPP group. This patients underwent standardized polysomnographic recordings. The anthropometric data and polysomnographic data were analyzed, statistically. Results : Of all 50 patients, 30% were found to be positional OSA. BMI was significantly higher in the PP group(p<0.05). Total sleep time was significantly longer in the PP group (350.6$\pm$28.2min, 333.3$\pm$46.0min, (p<0.05). Sleep efficiency was high in the PP group(89.6$\pm$6.4%, 85.6$\pm$9.9%, p<0.05). Deep sleep was significantly higher and light sleep was lower in the PP group than in the NPP group but no difference was observed in REM sleep between the two groups. Apnea index(AI) and RDI were significantly lower( 17.0$\pm$10.6, 28.5$\pm$13.3, p<0.05) and mean arterial oxygen saturation was higher in the PP group(92.7$\pm$1.8%. p<0.05) than in the NPP group. Conclusion : Body position during sleep has a profound effect on the frequency and severity of breathing abnormalities in OSA patients. A polysomnographic evaluation for suspected OSA patients must include monitoring of the body position. Breathing function in OSA patients can be improved by controlling their obesity and through postural therapy.

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Clinical and Radiological Characteristics of Non-Tuberculous Bronchial Anthracofibrosis (비결핵성 기관지탄분섬유증의 임상적 특징과 방사선학적 특징)

  • Jang, See Jin;Lee, Sook Young;Kim, Suk Chan;Lee, So Young;Cho, Hyun Sun;Park, Ki Hoon;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak;Kim, Young Kyoon;Park, Hyun Jin
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.2
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    • pp.139-144
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    • 2007
  • Background: Bronchial anthracofibrosis, which is defined as bronchial narrowing with black pigmentation of the overlying bronchial mucosa, is frequently associated with tuberculosis. The aim of this study was to examine the relationship between bronchial anthrocofibrosis and to identify the clinical and radiological characteristics of non-tuberculous bronchial anthracofibrosis. Methods: All patients who showed bronchial anthracofibrosis in more than one segment on a bronchoscopic examination from January 2003 to July 2006 at Kangnam St. Mary's hospital were enrolled in this study. The underlying diseases, baseline clinical characteristics, characteristic findings on a computed tomogram (CT) of the chest, pathologic findings of the bronchial mucosa, and the clinical response to steroid therapy were analyzed retrospectively. Results: A total 54 patients (19 males, 35 females) were enrolled with a mean age of 75 years. The most common presenting symptoms were cough, sputum and dyspnea. The predominant X-ray findings were peribronchial soft tissue attenuation with or without calcification, mediastinal lymphadenopathy with or without calcification and atelectasis. Fourteen non-tuberculous anthracofibrosis patients were treated with steroid. Nine patients were improved clinically, and 6 patients were improved radiologically. Conclusion: Bronchial anthracofibrosis is frequently associated with various pulmonary diseases not only tuberculosis but also COPD pneumonia etc.

Protective Effect of Saengshik Supplementation on Lead Induced Toxicity in Rats (생식의 섭취가 납중독 흰쥐의 피해 경감에 미치는 영향에 관한 연구)

  • Oh, Young-Joo;Kim, Jae-Min;Song, Si-Wan;Ha, Hyo-Cheol;Kim, Hyun-Su
    • 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.