Preventive Effects of Several Chemicals Against Lethality of Recombinant Human Tumor Necrosis Factor
作者:
Nobuko Satomi,
Akiko Sakurai,
Ruriko Haranaka,
Katsuyuki Haranaka,
期刊:
Journal of Biological Response Modifiers
(OVID Available online 1988)
卷期:
Volume 7,
issue 1
页码: 54-64
ISSN:0732-6580
年代: 1988
出版商: OVID
关键词: Recombinant tumor necrosis factor;Antitumor activity;Glutathione;O2scavengers;Arachidonic cascade;Len-tinan
数据来源: OVID
摘要:
Toxicity has been observed in mice receiving recombinant human tumor necrosis factor (rhTNF). In the present experiments, several chemicals were used to determine whether they could prevent the lethality of rhTNF without impairing its antitumor activity. Injection of phospholipase A2, cyclooxygenase, and lipoxygenase inhibitors at the same time as rhTNF administration could prevent the lethality of rhTNF, but the antitumor activity was also reduced. Urinastatin and reduced glutathione could prevent the lethality while reducing the activity. In contrast, by pretreatment with O2scavengers, the lethality of rhTNF was markedly reduced without impairment of the antitumor activity of rhTNF. Antihistamines exerted no influence on the lethality of rhTNF. Histopathologic examinations have demonstrated that the capillaries of the tumor tissue show aggregation of platelets and formation of fibrin adherent to the vascular surface after TNF administration. Heparin or protamine revealed no effects against the lethality of rhTNF. These results strongly suggest that the arachidonic cascade is deeply related to the antitumor activity of TNF and its side effects. Pretreatment with O2scavengers, especially bismuth subnitrate, could prevent the lethality of rhTNF without impairing its antitumor activity.
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