• YAKHAK HOEJI
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• v.32 no.5
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• pp.351-361
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• 1988

The herbicide, paraquat, has caused numerous poisonings in man and farm animals since its interoduction. Althought the lungs are the primary sites of toxicological effect, other organs are also damaged, such as liver, heart, and kidney. The biochemical mechanisms responsible for the toxicity of the herbicide are not clearly understood. The purpose of the present study was to determine the hepatotoxity of paraquat in rats and the effects of glycyrrhizin on the paraquat toxicity. The experimental results are the followings. 1. The values of serum AST, ALT, LDH, ALP, glucose, and cholesterol were significantly increased in the paraquat administered group. 2. The TBA values in serum and liver were also increased in the treated group. 3. The biochemical parameters of serum, such as AST, ALT, LDH and TBA values, were significantly low in the paraquat plus glycyrrhizin group in comparison with that of the paraquat only. The above results suggest that the glycyrrhizin, somehow, detoxify the hepa to toxicity of paraquat in the experimenta-animals.

• Environmental Analysis Health and Toxicology
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• v.11 no.3_4
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• pp.11-16
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• 1996

Paraquat is a useful nonselective herbicide widely used throught the world. However accidental or intentional ingestion of the herbicide cause fatal pulmonary injuring. But there is not suitable antidote of paraquat intoxication and therapeutic agents now be used are not effective. So, in this study we intended to evaluate the inhibitory effects of acetylmannan from Dioscorea batalas on paraquat toxicity. 100mg/kg acetylmannan from wild or cultured Dioscorea bataras was administered orally to male SD rats for 3 days and the administration time interval was 24hours. After one hour of final administration, 50mg/kg paraquat was administered intraperitonially. After 24 hours, the biochemical parameters of blood and tissues were examined. In paraquat treated groups, sGPT, BUN, creatinine, ALP levels were increased by 2 to 4 times of normal values. However in acetylmannan from wild Dioscorea batatas treated groups, sGPT, BUN, creatinine, ALP levels in blood and lung tissue were significantly decreased to normal levels. In acetylmannan from cultured Dioscorea batatas treated groups, BUN, creatinine were significantly decreased to normal values, but not in sGPT, ALP levels. Therefore, we concluded that acetylmannan from wild Dioscorea batatas can be used as an. antidote of paraquat toxicity.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.117-123
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• 1998

Paraquat is a useful nonselective herbicide widely used throughout the world. However, accidental or intentional ingestion of the paraquat cause fetal pulmonary injuring. But there is not suitable antidote of paraquat intoxication and therapeutic agents now be used are not effective. So, in this study we intended to evaluate the inhibitory effects of DDB(dimethyl-4,4'dimethoxy-5,6,5',6'-dimethylene dioxyphenyl-2,2'-dicarboxylate) on paraquat toxicity. DDB (100mg/kg) was administered orally to SD rats lhr after paraquat(50mg/kg) injection. After 24 hours, the biochemical parameters of blood and tissues were examined. In paraquat treated groups sGPT, sGOT, BUN, creatinine, MDA and alkaline phosphatase levels in blood and MDA, glucose-6-phosphatase activity in tissues were elevated by 2 to 5 times of normal values. However in schizandrin treated groups, sGPT, sGOT, MDA and alkaline phosphatase activity in blood and MDA and glucose-6-phosphatase activity were significantly decreased to notmal levels but not in biochemical parameters of nephrotoxicity, BUN and creatinine levels. Therefore, we concluded that schizandrin can be used as an antidote of pulmono, hepatotoxicity of paraquat.

• 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.

• Environmental Analysis Health and Toxicology
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• v.10 no.3_4
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• pp.29-40
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• 1995

To investigate and evaluate the scavenging and antioxidative effects of various ftavonoids on paraquat induced pulmonary toxicity, in vivo and vitro tests of eight flavonoids(catechin, epicatechin, flayone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. In vitro test, inhibitory and antioxidative effects of lipoxygenase dependent lipidperoxidation, NADPH dependent cytochrome p-450 reductase to liver and lung microsome and superoxide anion production in rat peritoneal exudated macrophage were studied. In vivo test, biochemical parameters and cell population in bronchoalveolar lavage fluid(BALF) in mouse and rats after administration of paraquat and flavonoids were tested. The results are summerized as follows; 1. All flavonoids tested inhibited on NADPH dependent cytochrome p-450 reductase in liver and lung microsome. 2. All flavonoids tested showed the inhibitory effects on the superoxide anion production in rat peritoneal exudated macropharge. 3. Lactate dehydrogenase, acid phosphatase and total protein in BALF of mouse which increased by the administration of paraquat, decreased significantly by catechin, chrysin, morin and biochanin A. 4. Numbers of alveolar macropharge and PMN in BALF of rats which increased by the administration of paraquat decreased by all the tested flavonoids. Therefore, all flavonoids tested showed the useful compounds for scavenger and antioxidant on paraquat induced pulmonary toxicity.

• Environmental Analysis Health and Toxicology
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• v.10 no.1_2
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• pp.47-54
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• 1995

To investigate and evaluated the scavenging and antioxidative effects of various flavonoids on paraquat induced toxicity, in vivo and vitro tests of eight flavonoids (catechin, epocatechin, flavone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. The generation of reactive oxygen substances(ROS) in PMS-NADH system $H_2O_2$ induced hemolysis and lipidperoxidation to blood, NADPH dependent lipidperoxidation to liver and lung microsome by paraquat were studied.The results are summerized as follows; 1) In the concentration ranges from 3.3 to 9.8$\mu$M of catechin,epicatechin, quercetin and biochanin A removed the 50% of DPPH radical scavenging effects. 2) In the concentration ranges from 0.60 to 1.86 mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on superoxide anion which gernerated in PMA-NADH system. 3) In the concentration ranges from 0.12 to 0.49mM of catechin, epicatechin, quercetin and biochanin A showed the inhibitory and antioxidative activity on H202 which generated in PMA-NADH system. 4) In the concentration ranges from 0.6 x10$^{-5}$ to 6.3 x 10$^{-5}$mM of catechin, epicatechin, flavone, chrysin, quercetin and morin showed the inhibitory and antioxidative activity on $H_2O_2$ induced hemolysis to blood 5) All flavonoids tested exhibited inhibitory and antioxidative effects on paraquat induced liver and tung microsomal lipidperoxidation. Therefore, all flavonoids evaluated showed the useful compounds for scavenger and antioxidant on paraquat induced toxicity.

• Environmental Analysis Health and Toxicology
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• v.15 no.1_2
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• pp.7-12
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• 2000

Scavenging effects on paraquat induced toxicity were investigated by using methanol (MeOH) and ethylacetate (EtoAC) extracts of Lonicera japonica. The results are summerized as follows: 1. To Fe(III)-ADP-NADPH induced microsomal lipid peroixdation, MeOH and EtoAC extracts showed antioxidative activiies and inhibition ratio at 100 $\mu\textrm{g}$/$m\ell$ 44.4% and 73.8% respectively 2. To microsomal NADPH dependent cytochrome p -450 reductase in rat liver, MeOH and EtoAC extracts inhibited the enzyme activiies and inhibition ratio were 26.3% and 44.8% respectively. 3. Administration (30 mg/kg, iv) of paraquat to rats caused the marked elevation of GOT, GPT, LDH, ALP in the serum and lipid peroxides in the microsome as compared to the control group. Serum GTP, LDH, ALP and liver microsomal LPO were reduced significantaly by administration of MeOH extract. (1,000 mg/kg), EtoAC extract (40 mg/kg) and Silymarin (150 mg/kg) as compared to the paraquat group. From the results, MeOH and EtoAc exuacts. of Lonicera japonica showed the useful scavenger and reducer on the paraquat induced hepatotoxicty.

• Toxicological Research
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• v.13 no.4
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• pp.393-400
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• 1997

The effects of superoxide dismutase(SOD) and catalase on the toxicity of paraquat(PQ) were studied using diethyldithiocarbamate(DDC), 3-amino-1,2,4-triazole(AT) which are inhibitors of Cu, Zn-SOD and catalase in rats. Sprague Dawley rats were divide into 6 groups: control, DDC, PQ, AT, DDC+PQ, and AT+PQ group. The PQ (50 mg/kg body weight(BW); about half dose of $LD_{50}$) was administered with orally, otherwise AT(1.0g/kg BW) and DDC(1.0g/kg BW) were administered by intrperitoneal(iP) injection. The survival rate of rats in PQ+AT group was significantly decreased compared with PQ group while the difference of survival rate between DDC group and DDC+PQ group was not significant. The SOD activity after administration of DDC was decreased in liver, lung and kidney, but catalase activity was not changed. The catalase activity in liver, lung and kidney of AT treated rats was decreased, while SOD activity was not changed in this group. The effects of DDC and AT to the PQ toxicity was also observed in primary cultured rat Skin fibroblasts. The viable cells that was measured with MTT method, was decreased in AT+PQ treated group compared to PQ treated group, but the difference of cell viability between DDC treat group and DDC+PQ treated group was not observed. This result, AT potentlate PQ toxicity while DDC were not affect, suggested that the decreased catalase activity lead to elevation of hydrogen peroxide levels and PQ toxicity may be correlate with the hydrogen peroxide rather than the superoxides.

• Toxicological Research
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• v.9 no.1
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• pp.23-33
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• 1993

In the present study, the effects of allopurinol on paraquat toxicity were investigated in paraquat-treated rats. The surivals of paraquat-treated rats were increased by allopurinol treatment. The contents of glutathione in liver and kidney were significantly decreased by paraquat, but restored by allopurinol. The activity of xanthine oxidase was significantly reduced but NADH dehydrogenase was not changed by allopurinol teatment. The activities of catalase, SOD and glutathione peroxidase in liver were significantly decreased by paraquat but catalase was restored by allopurinol treatment.

• Environmental Analysis Health and Toxicology
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• v.14 no.3
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• pp.95-101
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• 1999

The scavenging effects of two hyaroxycinnamic acids such as caffeic acid and chlorogenic acid on paraquat induced pulmonary toxicity were investigated. The results are summerized as follows: 1. In the 5-lipoxygenase assay, caffeic acid and chlorogenic acid inhibited the enzyme activities whose inhibition concentration (IC$\_$50/) were 4.1 and 9.6 ${\mu}$M respectively. 2. To evaluate the antiinflammatory effects on mediator related to the mechanism of inflammation, ADP-induced platelet aggregation assay and histamine degranulation assay were used. Caffeic acid and chlorogenic acid inhibited on ADP-induced platelet aggregation and histamine release at a concentration dependent manners. 3. Arachidonic acid-induced ear edema were inhibited by administration of caffeic acid and chlorogenic acid. 4. Cytologicad analysis of branchoalveolar lavage fluid (BALF) which was the useful tool for detection of an inflammatory response in the lungs of animals intoxicated with chemicals were used. Alveolar macrophages and neutrophils in BALF, as well as the protein content and the LDH activity in BALF supernatant increased by intoxication of paraquat, but decreased by administration of caffeic acid and chlorogenic acid. Therefore, two hydroxyeinnamic acids tested were the useful candidates for scavenger and antiinflammatory agents on paraquat induced pulmonary toxicity.