Japanese modified traditional Chinese medicines as preventive drugs of the side effects induced by tumor necrosis factor and lipopolysaccharide.
It was found that the capacity for tumor necrosis factor (TNF) production by Japanese modified traditional Chinese medicines and crude drugs broadly paralleled their antitumor activity. Pretreatment with these drugs prevented the lethal and marked side effects of recombinant human TNF (rhTNF) and lipopolysaccharide (LPS) without impairing their antitumor activity. These drugs are thought to decrease the oxygen radicals and stabilize the cell membranes, with a deep relation to the arachidonic cascade. The release of prostaglandins and leukotriene B4 was suppressed by pretreatment with Shosaiko-to. Thromboxane B2 was transiently increased, followed by suppression. After pretreatment with Hochu-ekki-to or Juzen-taiho-to, suppression of leukotriene B4 could not be observed. The release of prostaglandin D2 was suppressed in mice pretreated with Shosaiko-to, Juzentaiho-to or Ogon (Scutellariae Radix) but it increased following pretreatment with Hochu-ekki-to. Chemicals that could prevent the lethality of rhTNF and LPS also revealed suppression of prostaglandins, leukotriene B4 and thromboxane B2. In general, drugs that prevented the lethality of rhTNF and LPS without impairing the antitumor activity could inhibit the release of leukotriene B4 and/or prostaglandin D2. rhTNF could activate the arachidonic cascade in combination with LPS. The lethality of rhTNF and LPS could be prevented by pretreatment with Japanese modified traditional Chinese medicines and the crude drug, Ogon.
Satomi
N
N
Department of Internal Medicine, University of Tokyo, Japan.
Sakurai
A
A
Iimura
F
F
Haranaka
R
R
Haranaka
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000097:blood*; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal; D007564:Japan; D008070:Lipopolysaccharides / Q000627:therapeutic use*; D008516:Medicine, Chinese Traditional; D051379:Mice; D012509:Sarcoma / Q000188:drug therapy / Q000517:prevention & control; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C461320:shosaiko-to