氯仿中毒，glutathione (穀胱甘肽) depletion (耗盡), 台北榮總 [2013-01-29](IR91)

氯仿中毒，glutathione (穀胱甘肽) depletion (耗盡), 台北榮總 [2013-01-29](IR91)

Source:
http://www.pcc.vghtpe.gov.tw/old/docms/50123.htm

氯仿(chloroform)中毒

長庚醫院 張玉龍醫師

簡介

近來台北榮總毒物中心接到數名氯仿中毒的個案。氯仿(chloroform, trichloromethane, ChCl3)自西元1847年起，曾被用於吸入性麻醉劑用途；然因其肝毒性較大，自西元1912年後，即不建議用於醫療用途。氯仿在工業上，可被用於樹脂、橡膠製造之溶劑、黏著劑、穀物燻蒸除蟲劑。在實驗室中則常用以萃取DNA, RNA及脂肪。氯仿乃一無色可揮發性液體，聞起來似乙醚味，嚐起來帶點甜味，具X光不透性。

歷年個案統計

根據台北榮總毒物諮詢中心之統計，自民國75年起至87年6月止，共有20個個案。其中男、女各半，中毒者年齡由9歲至76歲不等。其中服食氯仿自殺者有5位，這其中有1人因服食較大量而死亡；有6人係誤將氯仿當成開水服食，這6人症狀大多為噁心、嘔吐、上腹痛及喉嚨不適；另有6人係皮膚不小心接觸氯仿，大多數僅產生輕微灼熱感，但其中有一人引起接觸性皮膚炎，另一人則引起化學性肝炎。有2人係於工作時吸入氯仿，導致呼吸困難、噁心、頭痛及全身無力；尚有一人因氯彷不慎濺及眼睛，導致眼部灼熱疼痛。

作用機轉

氯仿進入體內後迅速被吸收，且快速分布於體內各組織尤其是脂肪組織，主要以其代謝物二氧化碳經由肺部排出。

氯仿(三氯甲烷)經由肝臟之p450酵素系統形CCL3OH，其後再分解成鹽酸和有毒的光氣COCL2 (phosgene)。光氣隨即和水作用釋出二氧化碳及形成氯離子Cl-。氯離子則和肝臟的glutathione (穀胱甘肽) 作用形成最終產物。當氯仿吸收量過多時，可導致體內的glutathione (穀胱甘肽) 量缺乏，而導致肝、腎之傷害。

臨床症狀

氯仿可經由吸入、口服或皮膚接觸而致中毒。氯仿係一刺激劑，對中樞神經系統及心臟系統會產生抑制作用，並可對肝、腎造成毒性。文獻上曾有人攝食10cc即導致昏迷、死亡。
五官：對眼睛可造成灼熱疼痛、結膜炎及角膜傷害。常導致口乾及喉嚨不適。
心臟血管系統：過量可致心律不整而致死，血壓降低。
呼吸系統：可產生呼吸抑制、吸入性肺炎或肺水腫。
神經系統：頭痛、全身無力、意識不清。
胃腸症狀：噁心、嘔吐及上腹疼痛。
肝、腎毒性：于食入10至48小時內，即可導致肝細胞壞死。且可致腎功能變差，甚至腎衰竭。
血液方面：可致溶血、白血球上升及凝血時間prothrombin降低(PT延長)。
皮膚：產生刺激感、灼傷或皮膚壞死。
治療

將患者移除暴露源，且依其症狀來治療。
皮膚接觸：脫去受沾染之衣服，並用水沖洗。
眼睛接觸：用大量清水沖洗眼睛至少15分鐘。
口服：避免催吐。若剛食入，可考慮洗胃及給予活性碳治療，惟須注意呼吸道之保護，避免吸入性肺炎。口服致命劑量就成人來說，約每公斤0.5至5公克。
吸入性傷害：移至新鮮空氣處，監測呼吸情形，若有呼吸不適，則給予100%氧氣。
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Inflammatory Response and Oxidate Stress in the Degeneration of Dopamine Neurons in Parkinson's Disease [2003](IR91)_P01.png

Inflammatory Response and Oxidate Stress in the Degeneration of Dopamine Neurons in Parkinson's Disease [2003](IR91)_P01.png

Glutathione (穀胱甘肽) deficiency (缺乏，不足，短缺) in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis (肺纖維化). [1989](IR91)

Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.

Glutathione (穀胱甘肽) deficiency (缺乏，不足，短缺) in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis (肺纖維化). [1989](IR91)

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Glutathione (穀胱甘肽) deficiency (缺乏，不足，短缺) in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis (肺纖維化). [1989](IR91)

http://www.ncbi.nlm.nih.gov/pubmed/2913886
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Am Rev Respir Dis. 1989 Feb;139(2):370-2.

Glutathione deficiency (缺乏，不足，短缺) in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis (肺纖維化).

Cantin AM, Hubbard RC, Crystal RG.
Source
Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

Abstract
Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH), a sulfhydryl-containing tripeptide produced by most mammalian cells, is an efficient scavenger of toxic oxidants, including hydrogen peroxide, an oxidant that plays a major role in the oxidant burden placed on the epithelial surface of the lower respiratory tract in chronic inflammatory states. GSH is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant (抗氧化劑) protection to the epithelial cells. In this regard, we hypothesized that the lower respiratory tract of patients with IPF may be chronically depleted (耗盡) of this antioxidant (抗氧化劑), thus leading to an increased susceptibility of lung epithelial cells to oxidant injury. To evaluate this concept, the concentration of glutathione was determined in the epithelial lining fluid of the lower respiratory tract of 15 patients with IPF and compared to that of 19 normal subjects. Strikingly, whereas ELF glutathione concentrations were high in normal subjects (429 +/- 34 microM), a fourfold decrease was found in patients with IPF (97 +/- 18 microM, p less than 0.001). In the context of the known oxidant burden present in the lower respiratory tract of patients with IPF, these observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant (抗氧化劑) imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease.

PMID: 2913886 [PubMed - indexed for MEDLINE]
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Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.

http://www.ncbi.nlm.nih.gov/pubmed/2913886

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Am Rev Respir Dis. 1989 Feb;139(2):370-2.
Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis.
Cantin AM, Hubbard RC, Crystal RG.
Source
Pulmonary Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

Abstract
Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH), a sulfhydryl-containing tripeptide produced by most mammalian cells, is an efficient scavenger of toxic oxidants, including hydrogen peroxide, an oxidant that plays a major role in the oxidant burden placed on the epithelial surface of the lower respiratory tract in chronic inflammatory states. GSH is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant (抗氧化劑) protection to the epithelial cells. In this regard, we hypothesized that the lower respiratory tract of patients with IPF may be chronically depleted (耗盡) of this antioxidant (抗氧化劑), thus leading to an increased susceptibility of lung epithelial cells to oxidant injury. To evaluate this concept, the concentration of glutathione was determined in the epithelial lining fluid of the lower respiratory tract of 15 patients with IPF and compared to that of 19 normal subjects. Strikingly, whereas ELF glutathione concentrations were high in normal subjects (429 +/- 34 microM), a fourfold decrease was found in patients with IPF (97 +/- 18 microM, p less than 0.001). In the context of the known oxidant burden present in the lower respiratory tract of patients with IPF, these observations of a "GSH deficiency" in IPF ELF suggest that there is a marked oxidant-antioxidant (抗氧化劑) imbalance at the alveolar surface of these persons, thus increasing the susceptibility to the severe epithelial cell damage characteristic of this disease.

PMID: 2913886 [PubMed - indexed for MEDLINE]
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Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome (成人呼吸窘迫症候群). [1991](IR91)

Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome (成人呼吸窘迫症候群). [1991](IR91)

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Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome (成人呼吸窘迫症候群). [1991](IR91)

http://www.ncbi.nlm.nih.gov/pubmed/1935300

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Chest. 1991 Nov;100(5):1397-403.

Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome (成人呼吸窘迫症候群).

Pacht ER, Timerman AP, Lykens MG, Merola AJ.

Source
Department of Internal Medicine, Ohio State University, Columbus.

Abstract
The adult respiratory distress syndrome (成人呼吸窘迫症候群) (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema. Reactive oxygen species such as hydrogen peroxide (過氧化氫) and hypochlorous acid (次氯酸) may play a key role in the pathogenesis of the acute lung injury. Glutathione (GSH) (穀胱甘肽) is a tripeptide (三肽, i.e. 三種胺基酸連在一起) that is able to react with and effectively neutralize oxidants such as hydrogen peroxide (過氧化氫) and hypochlorous acid (次氯酸). The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7 mumols +/- 7.8 mumols vs 91.8 mumols +/- 14.5 mumols; p = 0.002). In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 +/- 0.003 nmol of GSH per microgram of total protein vs 0.026 +/- 0.005 nmol of GSH per microgram of total protein; p = 0.002). Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of GSH may predispose (使容易...) these patients to enhanced lung cell injury (肺細胞損傷).

PMID: 1935300 [PubMed - indexed for MEDLINE]
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adult respiratory distress syndrome
成人呼吸窘迫症候群
adult respiratory distress syndrome (成人呼吸窘迫症候群)(ARDS)

acute respiratory distress syndrome
acute respiratory distress syndrome (ARDS)
急性呼吸窘迫症候群
acute respiratory distress syndrome (ARDS)(急性呼吸窘迫症候群)

呼吸, acute respiratory distress syndrome

肺炎併發急性呼吸窘迫症與敗血性休克
肺炎併發急性呼吸窘迫症與敗血性休克

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