Synthetic trehalose dicorynomycolate (S-TDCM): behavioral effects and radioprotection

Abstract

This study evaluated synthetic trehalose dicorynomycolate (S-TDCM), an immunomodulator, for its survival enhancing capacity and behavioral toxicity in B6D2F1 female mice. In survival experiments, mice were administered S-TDCM (25-400 micrograms/mouse i.p.) 20-24 hr before 5.6 Gy mixed-field fission-neutron irradiation (n) and gamma-photon irradiation. The 30-day survival rates for mice treated with 100-400 micrograms/mouse S-TDCM were significantly enhanced compared to controls. Toxicity of S-TDCM was measured in nonirradiated mice by locomotor activity, food intake, water consumption, and alterations in body weight. A dose-dependent decrease was noted in all behavioral measures in mice treated with S-TDCM. Doses of 100 and 200 micrograms/mouse S-TDCM significantly reduced motor activity beginning 12 hr postinjection with recovery by 24 hr. A dose of 400 micrograms/mouse significantly decreased activity within the first 4 hr after administration and returned to control levels by 32 hr following injection. Food and water intake were significantly depressed at doses of 200 and 400 micrograms/mouse on the day following drug administration, and were recovered in 24 hr. Body weight was significantly decreased in the 200 micrograms/mouse group for 2 days and in the 400 micrograms/mouse group for 4 days following injection. A dose of 100 micrograms/mouse effectively enhanced survival after fission-neutron irradiation with no adverse effect on food consumption, water intake, or body weight and a minimal, short-term effect on locomotor activity.