Radioprotective efficacy of HT + AET in encapsulated form.

Entrapment of 5-hydroxyl-L-tryptophan (HT) in erythrocyte ghost prepared by hypotonic method and high voltage electric discharge method are nearly same. Release of HT with beta-aminoethylisothiuronium bromide hydrobromide (HT + AET) in in vitro system is rapid but only a portion of the entrapped amount is released. Release of HT + AET in serum marginally increases at 2 hr. Compared to release in in vitro medium the release in serum is less. Survival studies with Swiss albino mice indicates that compared to HT alone, the combination of HT + AET shows about 9 times percentage survival. The same combination in the encapsulated form show comparable percentage survival though the amount needed is 1/200th times compared to free form.

Use of hydroxylamine in improving radio protection of a combination of 5-hydroxy L-tryptophan and a thiol compound (AET) in small mammals.

Radioprotective effectiveness has been evaluated by 30 day survival studies and protection to bone-marrow cells in mice after radiation exposure and this has been further established by 24 hr deoxycytidine excretion in urine of rats following 5 Gy whole body gamma irradiation and protection to superoxide dismutase enzyme in marrow cells and red blood corpuscles. Radioprotective effectiveness as well as the duration of radioprotection have been improved by the administration (ip) of hydroxylamine (20 mg/kg), a decarboxylase inhibitor, prior to the use of a combination of 5-hydroxy L-tryptophan (5-HTP, 70 mg/kg) and 2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg) ip in small mammals before whole body gamma irradiation.

Effect of some chemical radioprotectors on mouse bone marrow.

Effect of HT, AET and Se on mice bone marrow has been studied by counting bone marrow micronucleated cells and endogenous spleen colony count (CFU-S). Combination of HT and AET used as a radioprotector has not caused any significant variation in any of the parameter studied when administered once, it increases bone marrow micronucleated cells and decreases CFU-S slightly after daily administration for 7 days. The individual constituent of the combination administered singly does not increase micronucleated cell number. Seven consecutive doses of HT + AET and same in combination with Se enhances micronucleated cells to a higher level. Daily injection of Se alone up to 7 days also causes an increase in micronucleated cells upto same level. CFU-S pool does not show any significant change in number of bone marrow cells through out the study except in the groups where animals were treated with Se.

Protection to glycolysis by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats.

Rate of glycolysis in vivo at different time intervals following 8 Gy [LD100(30)] whole body gamma radiation (WBGR) was evaluated by estimating liver glycogen, blood sugar, serum lactic dehydrogenase (LDH) and blood lactic acid concentration in adult male Sprague Dawley rats. Within 1 hr of radiation exposure, a significant fall in liver glycogen was observed in rats fed food and water ad libitum. The glycogen content increased after 24 hr and had returned to control level on 7th day after radiation exposure. Blood sugar, serum LDH and blood lactate levels increased significantly as compared to non irradiated controls. Pretreatment with 5-hydroxy-L-tryptophan (5-HTP; 100 mg/kg) + 2-aminoethylisothiuronium bromide hydrobromide (AET; 20 mg/kg) ip 30 min before 8 Gy WBGR, modified these values and restored them to normal level on 7th day post-irradiation.