[Protective effect of GSH and MEA on mitotic delay induced by treatment with superoxide generated by xanthine-xanthine oxidase system (author's transl)].
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The capacity of radioprotectors (serotonin, aminoethylisothiuronium) to stimulate in radioprotective doses cAMP-dependent protein phosphorylation of the cytozol and nuclei of the mouse liver and of the spleen cytozol was shown in vivo. Radioprotectors were incapable of modulating in vitro the activity of protein kinases and the stimulating effect of cAMP. The data presented and previous investigations suggest that the activation of cAMP-dependent phosphorylation by radioprotectors was due to the increase of intracellular cAMP concentration under the effect of radioprotectors.
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Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance. A 1 mg dose of untreated endotoxin, injected i.p. into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality. The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray. Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin. Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge. This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation. The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen. At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin. Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease. In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin. Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin.
In experiments set up on mice, rats and guinea pigs 8 gamma-pyron derivatives were studied. They proved to be little toxic, do not change significantly the arterial pressure and respiration, exercise a depressing action on the central nervous system, produce a marked antiphlogistic (normal and irradiated animals), radio-protective and antihistaminic effects and influence norephinephrine, homovanillic acid and dopamine metabolism in the brain.
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