A decrease in carboplatinum hemotoxicity was detected in experiments on C57B1 mice treated with the drug in combination with indralin (urgent radioprotector). Carboplatinum in a dose of 125 mg/kg, injected intraperitoneally, caused 80-100% death; the median term of death was 6 days (3-17). Single oral dose of indralin (100 mg/kg) during the 1st min or 15 min after carboplatinum injection (125 mg/kg) increased animal survival by 40.0-46.7% by day 20 of the experiment primarily during the period of manifest hemotoxicity (days 7-17), indralin injected 1, 2, or 4 h after carboplatinum exhibited no chemoprotective effect.

Daily treatment of outbred albino mice with gammafos in radioprotective doses of 300 and 500 mg/kg for 4 days produced a cumulative toxic effect. This effect was not observed after decreasing the dose of gammafos to 100 mg/kg. Repeated peroral administration of melatonin and ascorbic acid in a dose of 200 mg/kg 30 min before treatment with gammafos reduced its cumulative toxic effect. Succinic acid in a dose of 100 mg/kg was ineffective under these conditions. The cumulative death time for 50% animals receiving gammafos alone or in combination with melatonin, ascorbic acid, and succinic acid was 3.08, 4.29, 4.06, and 2.97 days, respectively.

The therapeutic radiomitigating effect of cystamine and indralin was studied in experiments on mice and rats and pharmacological analysis of these drugs was carried out. The animals were subjected to whole-body Co γ-irradiation. The mice were exposed to single (9-10 Gy) or double (8 Gy) irradiation with an interval of 1 month. The rats were exposed to 10 Gy with partial shielding of the upper quarter of the abdomen. In experiments on mice, pretreatment with reserpine abolished the therapeutic effect of cystamine administered repeatedly every 15 min over 1 h after irradiation. Moreover, summation of the radioprotective and therapeutic effects of the radioprotector was revealed under these conditions. In mice and rats, α-adrenoreceptor blocker terazosin did not abolish the therapeutic effect of indralin administrated after irradiation, but blocked the radioprotective effect of indralin applied prior to irradiation. At the same time, 5-HT serotonin receptor blocker tropoxin abolished the therapeutic effect of indralin without affecting its radioprotective activity.

No abstract

Female rats were exposed to local γ-irradiation of the right hindpaw in doses of 30-50 Gy at 131-154 sGy/min dose rate. Radioprotector indralin was administered per os 15 min prior to irradiation, monizol was injected intraperitoneally 5 min after irradiation. Indralin showed marked radioprotective properties both for acute and delayed symptoms of local radiation injuries. In combination with monizol, radioprotective effect of indralin was potentiated to dose reduction factor of 1.4-1.5 both for radiation burn severity reduction and for restriction of postradiational contracture development and amputation of the irradiated limb.