Radioprotection of hemopoiesis conferred by Acanthopanax senticosus Harms (Shigoka) administered before or after irradiation

Abstract

Acanthopanax senticosus Harms (Shigoka) extract has been observed to have radioprotective effects on hemopoiesis of irradiated mice (CBA/olac) when administered before or after irradiation by 60Co. The mechanisms of action were explored by studying the following parameters: 1) survival after lethal doses of irradiation; 2) recovery of spleen colony-forming units (CFU-S); 3) protective effect on endogenous CFU-S; and 4) effect on self-renewal of CFU-S. 1) The 30-day mortality due to bone marrow failure after irradiation was significantly reduced in Shigoka-treated mice. The maximum effect of the extract (80% survival) at a dose of 5 mg was observed when given intraperitoneally 24 h before a lethal dose of irradiation (9.5 Gy) and it was still effective when administered as late as 12 h after irradiation (30% survival). The radioprotective effect of Shigoka extract given before irradiation was not due to an increase in the total number of CFU-S but probably due to quiescent CFU-S that entered DNA synthesis (S-phase) 24 h after the injection of Shigoka extract. 2) Recovery of CFU-S in mice given the extract within 15 min after 4.75 Gy of whole body irradiation was also enhanced, especially in the spleen. The number of CFU-S in the bone marrow 24 h after irradiation showed a marked decrease. It returned to normal values in the bone marrow at day 11 in Shigoka-treated mice and at day 15 in nontreated irradiated mice. CFU-S in the spleen recovered more rapidly with an overshoot from days 7 to 21 in the Shigoka-treated mice, whereas in control irradiated mice it did not reach the normal value until day 21. 3) Nine days after sublethal doses of irradiation (7.0 Gy) the number of endogenous spleen colonies (endogenous CFU-S) was highest in mice given the extract 24 h before irradiation. The extract administered as late as 24 h after irradiation also resulted in an increase of the endogenous CFU-S. 4) The number of CFU-S in each 9-day endogenous CFU-S was 73.9 +/- 7.2 per nodule in treated mice and 0.2 +/- 0.1 per nodule in irradiated control mice, which suggests increased self-renewal of CFU-S in Shigoka-treated groups. These results suggest that the radioprotection conferred by Shigoka extract results from enhanced stimulation of CFU-S not only toward proliferation but also toward CFU-S self-renewal. These two phenomena could explain the protective effects of Shigoka extract administered even after irradiation.