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抗炎药预处理对大鼠百草枯毒性的影响。

Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat.

作者信息

Reddy K A, Litov R E, Omaye S T

出版信息

Res Commun Chem Pathol Pharmacol. 1977 May;17(1):87-100.

PMID:877407
Abstract

Aspirin (ASA), indomethacin (IND), hydrocortisone (HYC) or 0.25% agar (control) were administered (p.o.) daily to rats for 5 days. Following drug pretreatments, the activities of cytosolic superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) were elevated 30-70%, 5-25% and 8-25%, respectively. In a second experiment, rats pretreated as above were injected (ip) on the 5th day with paraquat (PQ) (29 mg/kg). Rats in each group expired more ethane 2 hours after PQ injection. After 22 hours, expired ethane returned to zero time levels. All control rats died within 48 hours after PQ injection. At the end of 48 hours, rats pretreated with ASA, IND, or HYC demonstrated survival rates of 13%, 31%, and 47%, respectively. PQ injection produces marked elevations of SOD (82%), GP (328%), and GR (36%) in the lungs of PQ-injected controls rats over non-PQ injected controls. Elevation of these enzymes were also noted in drug-treated rats after PQ injection but at values less than PQ-injected controls. Anti-inflammatory drugs were tested in rat liver homogenates for their ability to inhibit thiobarbituric acid (TBA) reactive product formation. Only the addition of HYC resulted in a decrease formation of TBA-reactive products. Thus in vitro studies suggest that the antiinflammatory drugs tested, other than HYC, may have other mechanisms of actions in addition to inhibition of lipid peroxides.

摘要

将阿司匹林(ASA)、吲哚美辛(IND)、氢化可的松(HYC)或0.25%琼脂(对照)每日经口给予大鼠,持续5天。药物预处理后,胞质超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GP)和谷胱甘肽还原酶(GR)的活性分别升高了30 - 70%、5 - 25%和8 - 25%。在第二个实验中,按上述方法预处理的大鼠在第5天腹腔注射百草枯(PQ)(29 mg/kg)。每组大鼠在PQ注射后2小时呼出更多乙烷。22小时后,呼出的乙烷恢复到零时水平。所有对照大鼠在PQ注射后48小时内死亡。在48小时结束时,用ASA、IND或HYC预处理的大鼠存活率分别为13%、31%和47%。与未注射PQ的对照大鼠相比,注射PQ的对照大鼠肺中SOD(82%)、GP(328%)和GR(36%)显著升高。PQ注射后,在药物处理的大鼠中也观察到这些酶的升高,但数值低于注射PQ的对照大鼠。在大鼠肝匀浆中测试了抗炎药物抑制硫代巴比妥酸(TBA)反应性产物形成的能力。只有加入HYC导致TBA反应性产物形成减少。因此,体外研究表明,除HYC外,所测试的抗炎药物除了抑制脂质过氧化外,可能还有其他作用机制。

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Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat.抗炎药预处理对大鼠百草枯毒性的影响。
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引用本文的文献

1
Lack of in vivo lipid peroxidation in experimental paraquat poisoning.实验性百草枯中毒中体内脂质过氧化的缺乏
Naunyn Schmiedebergs Arch Pharmacol. 1980 Jan;310(3):241-3. doi: 10.1007/BF00499917.
2
Paraquat: model for oxidant-initiated toxicity.百草枯:氧化应激引发毒性的模型。
Environ Health Perspect. 1984 Apr;55:37-46. doi: 10.1289/ehp.845537.
3
Biological and methodological implications of prostaglandin involvement in mouse brain lipid peroxidation measurements.前列腺素参与小鼠脑脂质过氧化测量的生物学和方法学意义。
Neurochem Res. 1989 Mar;14(3):217-20. doi: 10.1007/BF00971313.