Glutathione uptake after intraperitoneal administration and glutathione radiopharmacology after rectal administration, in mice.

Glutathione is a biologic aminothiol radioprotector. Hydrolysis of exogenous glutathione takes place in the extracellular compartment and leads to two metabolites: gamma-glutamylcysteine and glycine. In healthy mice, after an intraperitoneal administration of glutathione, all organs absorb the gamma-glutamylcysteine and the glycine with variable kinetics according to their enzymatic equipment. The rectal administration of glutathione in mice previously irradiated at the pelvic region, increases the availability of glutathione in the rectum and in other organs at a distant from the irradiation site. This contribution could be used to protect the rectum and the uterus during therapeutic irradiation.

2-Mercapto-propylamine: radiopharmacology in mice, pharmacokinetic studies in mice and in rats, mutagenicity and differential distribution between tissues and EMT6 tumour in mice.

Radiopharmacological studies conducted with 2-mercapto-propylamine (2MPA), a methylated derivative of cysteamine, indicated a good efficiency in whole body irradiated mice as observed over a period of 9 months. Its efficacy was also checked for supralethal irradiations of restricted body parts: in the brain and the rectum. The diffusion of 14C-labelled 2MPA was assessed by an autoradiographic study and measurement of its distribution in the main organs in mice. 2MPA penetrated the blood brain barrier but concentrated preferentially in the liver, kidney and skin. Fixation on plasmatic proteins was much lower in rats than in mice but urinary and faecal eliminations were of the same order for the two species. An important biliary excretion of 2MPA or its metabolites in rats combined with their lack in the faeces underlies an entero-hepatic cycle. A differential diffusion of 2MPA between normal tissues in mice and EMT6 tumours was clearly revealed by autoradiographic observations. The ability of 2MPA to trap 2,2'-diphenyl 1-picryl hydrazyl, an organic free radical, was checked by in vitro studies. Its performance indicated that 2MPA acted at least as a free radical scavenger. Ames test demonstrated that 2MPA whatever the dose employed was not a mutagenic agent. Pharmacological and pharmacokinetical observations provided a better understanding of the activity of this drug.

The radioprotective power of 2-isopropyl 5-methyl 1,3-thiazolane.

The adequate conditions of radioprotective treatment with 2-isopropyl 5-methyl 1,3-thiazolane were established for mice. Protection is maximum with a unique intraperitoneal injection of LD 50/2, 3 hours prior to the irradiation. The rate of radiation dose reduction is therefore 1.75. Survival rate of whole body irradiated mice with supralethal doses were determined for 11 months. The long term survival of the animals fully proved good prevention of radio-induced damages. In vitro pharmacological studies show the ability of the major metabolite of the compound to trap organic radicals.