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폐와 간조직의 산화성 손상에 대한 Deferoxamine의 항산화 효과에 관한 연구
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폐와 간조직의 산화성 손상에 대한 Deferoxamine의 항산화 효과에 관한 연구.hwp
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폐와 간조직의 산화성 손상에 대한 Deferoxamine의 항산화 효과에 관한 연구.hwp
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자료설명
산화제는 산소의 불안정한 대사산물로서 강력한 산화성 작용을 지니고 있으며, 과산화물(02-), 과산화수소 및 수산기(OH⋅) 등이 ...
본문/내용
산화제는 산소의 불안정한 대사산물로서 강력한 산화성 작용을 지니고 있으며, 과산화물(02-), 과산화수소 및 수산기(OH⋅) 등이 있는데 패혈증, 허혈-재관류, 화상 등의 질환에서 많이 분비되는 것으로 알려져 있다(Cross et al., 1987; Heffner & Repine, 1989; Reilly et al., 1991). 이들 물질들은 세포막의 구성성분인 지질을 과산화시켜서 세포막의 손상과 더불어 세포내 기능상실을 유발시킨다. 이러한 산화제에 의한 폐조직의 지질과산화는 화상을 비롯한 여러 동물실험모델에서 증명되었다(Jin et al., 1986; Demling & Lalonde, 1990; Demling et al., 1991). Paraquat(1,1`-dimethyl-4, 4-bipyridylium dichloride)는 1958년 영국에서 처음으로 제초제로 사용된 이래 전세계적으로 널리 사용되어져 왔던 약제로, 사람과 동물이 중독시 독성이 치명적인 것으로 알려져 있다. Paraquat를 음독시 문제가 되는 것은 치료제로서 특별한 해독제가 없다는 사실과 음독 후 조기의 적극적인 치료, 예를 들면 장에서의 흡수를 줄이기 위하여 위장세척, 구토, 활성탄 투여 등의 방법과, 흡수된 혈중내의 paraquat을 제거하기 위하여 복막투석, 혈액투석, hemoperfusion, hemofiltration 등에도 불구하고 여전히 30-80% 정도의 높은 사망률을 보인다는 것이다(Bismuth et al., 1987; Proudfoot et al., 1987; Lheureux et al., 1995).
Paraquat에 의한 독성이 나타나는 기전은 산소유리기에 의한 것으로 보고되어 왔으며, 표유동물의 세포내에서 paraquat은 NADPH와 효소
촉매 작용에 의하여 paraquat radical(PQ+˙)로 환원된다. 이렇게 형성된 paraquat radical은 산소 분자와 반응하여 supero…
촉매 작용에 의하여 p…
촉매 작용에 의하여 p…
참고문헌
Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Bio Chem. 1952, 195:133.
Bismuth C, Scherrmann JM, Garnier R, et al. Elimination of paraquat. Human Toxicol. 1987, 6:63-67.
Burkitt MJ, Kadiiska MB, Hanna PM, et al. Electron spin resonance spin-trapping investigation into the effects of paraquat and deferoxamine on hydroxyl radical generation during acute iron poisoning. Molecular Pharmacology. 1992, 43:257-263.
Cross CE. Oxygen radicals and human disease. Ann Int Med. 1987, 107:526-545.
Demling R, Lalonde C. Early postburn lipid peroxidation : effects of ibuprofen and allopurinol. Surgery. 1990, 107:85-93.
Demling R, Lalonde C. Early burn excision attenuates the postburn lung and systemic response to endotoxin. Surgery. 1990, 108:28-35.
Demling R, Lalonde C, Knox J, et al. Fluid resuscitation with deferoxamine prevents systemic burn-induced oxidant injury. J Trauma. 1991, 31:538-544.
Demling R, Seekamp A, Lalonde c, et al. Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep. J Appl Physiol. 1988, 65:1210-1216.
Deneki S, Berkley AL, Fanburg B. Transient depletion of lung glutathione by diethylmaleate enhance oxygen toxicity. J Appl Physiol. 1985, 58:571-574.
Griffith OW. Determination of glutathione and glutathine sulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem. 1980, 106:207-212.
Hallaway PE, Eaton J, Panter S, et al. Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci. 1989, 86:10108-12.
Halliwell B. Oxidants and human disease, some new concepts. FASEB. 1987, 1:358-364.
Heffer JE, Repine JE. Pulmonary strategies of antioxidant defense. Am Rev Resp Dis. 1989, 140:531-554.
Higenbottam T, Crome P, Parkinson C, et al. Further clinical observations on the pulmonary effects of paraquat ingestion. Thorax. 1979, 34:161-165.
Hudson M, Patel SB, Ewen SWB, et al. Paraquat induced pulmonary fibrosis in three survivors. Thorax. 1991, 46:201-204.
Im JG, Lee KS, Han MC, et al. Paraquat poisoning: findings on chest radiography and CT in 42 patients. AJR. 1991, 157:697-701.
Jin LJ, Lalonde C, Demling R. Lung dysfunction after thermal injury in relation to prostanoid and oxygen radical release. J Appl Physiol. 1986, 61:103-112.
Keller GA, Barke R, Harty JT. Decreased hepatic glutathione levels in septic shock. Arch Surg. 1985, 120:941-945.
Kohen R, Chevion M. Paraquat toxicity is enhanced by iron and reduced by deferrioxamine in laboratory mice. Biochem Pharmacol. 1985, 34:1841-1843.
Kosugi I, Tajimi K, Ohmura A, et al. New approachs to shock therapy: Reduced glutathione(GSH). Molecular & cellular aspects of shock & trauma. Alan R Liss, Inc, New York. 1983, 253-269.
Lheureux P, Leduc D, Vanbinst R, et al. Survival in a case of massive paraquat ingestion. Chest. 1995, 107:285-89.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979, 95:351-358.
Proudfoot AT, Prescott LF, Jarvie DR. Hemodialysis for paraquat poisoning. Human Toxicol. 1987, 6:69-74.
Reilly PM, Schiller HJ, Bulkley GB. Pharmacologic approach to tissue injury mediated by free radical and other reactive oxygen metabolites. Am J Surg. 1991, 161:488-503.
Van der wal NAA, Van oirscchot JFLM, Van dijk AV, et al. Mechanism of protection of alvelolar type II cells against paraquat-induced cytotoxicity by deferoxamine. Biochem Pharmacol. 1990, 39:1665-1671.
Van der wal NAA, Smith LL, Van oirschot JFLM, et al. Effect of iron chelators on paraquat toxicity in rats and alveolar type II cells. Am Rev Respir Dis. 1992, 145:180-186.
Vaziri ND, Ness RL, Fairshter RD, et al. Nephrotoxicity of paraquat in man. Arch Intern Med. 1979, 139:172-174.
Ward P, Till G, Hatherhill J, et al. Systemic complement activation and products of lipid peroxidation. J Clin Invest. 1985, 176:517-527.
White CW, Jackson JH, McMurty IF, et al. Hypoxia increases glutathione redox cycle and products rat lungs against oxidants. J Appl Physiol. 1988, 65:2607-2616.
White CW, Ghezzi P, McMahons S, et al. Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia. J Appl Physiol. 1989, 66:1003-1007.
Yam j, Roberts RJ. Pharmacological alteration of oxygen induced lung toxicity. Toxico Appl Pharmacol. 1979, 47:367-375.
Youn YK, Lalonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg. 1992, 16:30-36.
Bismuth C, Scherrmann JM, Garnier R, et al. Elimination of paraquat. Human Toxicol. 1987, 6:63-67.
Burkitt MJ, Kadiiska MB, Hanna PM, et al. Electron spin resonance spin-trapping investigation into the effects of paraquat and deferoxamine on hydroxyl radical generation during acute iron poisoning. Molecular Pharmacology. 1992, 43:257-263.
Cross CE. Oxygen radicals and human disease. Ann Int Med. 1987, 107:526-545.
Demling R, Lalonde C. Early postburn lipid peroxidation : effects of ibuprofen and allopurinol. Surgery. 1990, 107:85-93.
Demling R, Lalonde C. Early burn excision attenuates the postburn lung and systemic response to endotoxin. Surgery. 1990, 108:28-35.
Demling R, Lalonde C, Knox J, et al. Fluid resuscitation with deferoxamine prevents systemic burn-induced oxidant injury. J Trauma. 1991, 31:538-544.
Demling R, Seekamp A, Lalonde c, et al. Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep. J Appl Physiol. 1988, 65:1210-1216.
Deneki S, Berkley AL, Fanburg B. Transient depletion of lung glutathione by diethylmaleate enhance oxygen toxicity. J Appl Physiol. 1985, 58:571-574.
Griffith OW. Determination of glutathione and glutathine sulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem. 1980, 106:207-212.
Hallaway PE, Eaton J, Panter S, et al. Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci. 1989, 86:10108-12.
Halliwell B. Oxidants and human disease, some new concepts. FASEB. 1987, 1:358-364.
Heffer JE, Repine JE. Pulmonary strategies of antioxidant defense. Am Rev Resp Dis. 1989, 140:531-554.
Higenbottam T, Crome P, Parkinson C, et al. Further clinical observations on the pulmonary effects of paraquat ingestion. Thorax. 1979, 34:161-165.
Hudson M, Patel SB, Ewen SWB, et al. Paraquat induced pulmonary fibrosis in three survivors. Thorax. 1991, 46:201-204.
Im JG, Lee KS, Han MC, et al. Paraquat poisoning: findings on chest radiography and CT in 42 patients. AJR. 1991, 157:697-701.
Jin LJ, Lalonde C, Demling R. Lung dysfunction after thermal injury in relation to prostanoid and oxygen radical release. J Appl Physiol. 1986, 61:103-112.
Keller GA, Barke R, Harty JT. Decreased hepatic glutathione levels in septic shock. Arch Surg. 1985, 120:941-945.
Kohen R, Chevion M. Paraquat toxicity is enhanced by iron and reduced by deferrioxamine in laboratory mice. Biochem Pharmacol. 1985, 34:1841-1843.
Kosugi I, Tajimi K, Ohmura A, et al. New approachs to shock therapy: Reduced glutathione(GSH). Molecular & cellular aspects of shock & trauma. Alan R Liss, Inc, New York. 1983, 253-269.
Lheureux P, Leduc D, Vanbinst R, et al. Survival in a case of massive paraquat ingestion. Chest. 1995, 107:285-89.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979, 95:351-358.
Proudfoot AT, Prescott LF, Jarvie DR. Hemodialysis for paraquat poisoning. Human Toxicol. 1987, 6:69-74.
Reilly PM, Schiller HJ, Bulkley GB. Pharmacologic approach to tissue injury mediated by free radical and other reactive oxygen metabolites. Am J Surg. 1991, 161:488-503.
Van der wal NAA, Van oirscchot JFLM, Van dijk AV, et al. Mechanism of protection of alvelolar type II cells against paraquat-induced cytotoxicity by deferoxamine. Biochem Pharmacol. 1990, 39:1665-1671.
Van der wal NAA, Smith LL, Van oirschot JFLM, et al. Effect of iron chelators on paraquat toxicity in rats and alveolar type II cells. Am Rev Respir Dis. 1992, 145:180-186.
Vaziri ND, Ness RL, Fairshter RD, et al. Nephrotoxicity of paraquat in man. Arch Intern Med. 1979, 139:172-174.
Ward P, Till G, Hatherhill J, et al. Systemic complement activation and products of lipid peroxidation. J Clin Invest. 1985, 176:517-527.
White CW, Jackson JH, McMurty IF, et al. Hypoxia increases glutathione redox cycle and products rat lungs against oxidants. J Appl Physiol. 1988, 65:2607-2616.
White CW, Ghezzi P, McMahons S, et al. Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia. J Appl Physiol. 1989, 66:1003-1007.
Yam j, Roberts RJ. Pharmacological alteration of oxygen induced lung toxicity. Toxico Appl Pharmacol. 1979, 47:367-375.
Youn YK, Lalonde C, Demling R. The role of mediators in the response to thermal injury. World J Surg. 1992, 16:30-36.
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