Improved fertility through superoxide removal by Toki-shakuyaku-san in mice--a preliminary study

The effect of a superoxide dismutase inhibitor on pregnancy rate and fetal survival, and the effect of concomitant treatment with Toki-shakuyaku-san, was studied. Twelve week-old IV CS female mice were given diethyldithiocarbamate (DEDC; 0.9, 9, 45, and 225 mg kg(-1)) intraperitioneally, from Day 3 to Day 5 of pregnancy, every 12 h, for a total of six times. Two additional groups received both 45 mg kg DEDC and Toki-shakuyaku-san (50 or 200 mg/100 mL), by water bottle, from 12 h before to 12 h after DEDC administration. For each group, the pregnancy rate, the number of surviving fetuses, and the number of resorbed fetuses was calculated. Pregnancy rates were 95.5, 81.8, 54.5 and 0%, respectively, in the DEDC groups and were 100% in the control group. The fetal resorption rate was 0.9 in the control group, and 1.0, 1.7, and 2.3, respectively, in the 0.9, 9, 45 mg kg(-1) DEDC groups. Administration of 200 mg Toki-shakuyaku-san significantly (P<0.05) improved the pregnancy rate to 81.8%, and improved the degree of reduced intercellular interactions and insufficient decidual reactions found on Day 5 in the endometrium of the DEDC groups. Toki-shakuyaku-san reduces the adverse effects of excess superoxides on the endometrium during implantation.