The Zishen Yutai pill shows no reproductive toxicity on embryo-fetal development in rats and rabbits

Abstract

Objective: the Zishen Yutai pill (ZYP) is one of the most commonly used Chinese medicines to prevent miscarriage. However, its safety during pregnancy remains ill-defined. In this study, we aimed to investigate the potential reproductive toxicity of ZYP on embryo-fetal development. Methods: various doses of ZYP were given to pregnant rats (6, 12 and 24 g kg −1 d −1 ; i.e. 24×, 48× and 96× clinical doses) and rabbits (1.5, 3.0 and 6.0 g kg −1 d −1 ; i.e. 6×, 12× and 24× clinical doses) by intragastric administration for the period from implantation to hard palate closure. Physiological saline and cyclophosphamide were used as negative and positive controls, respectively. Maternal effects on weight loss, implantation failure and fetal resorption as well as effects on fetal physical growth and congenital malformations were recorded.Results: both maternal and fetal toxicities were observed in rats and rabbits after cyclophosphamide exposure, including lower maternal weight (not in rabbits), decreased rate of live fetuses, increased rate of fetal resorption, inhibited fetal physical growth and higher rate of malformation. However, adverse effects such as significantly lower extra-uterine weight gain and decreased food intake during GD 6-7 were only detected in rats after exposure to ZYP at the dose of 24 g kg −1 d −1 , while no severe effects were found in all ZYP treated rabbits. Conclusions: ZYP exhibited no reproductive toxicity on embryo-fetal development at the dose of 12 g kg −1 d −1 for rats and 6 g kg −1 d −1 for rabbits. Consequently, ZYP can be safely used at the clinical dose.

Reproductive Toxicity of Zishen Yutai Pill in Rats: The Fertility and Early Embryonic Development Study (Segment I)

“…Herein, we begin to address this issue for ZYP in three reproductive toxicology studies in succession, including its effects on fertility and early embryonic development in rats (segment I), embryo-fetal development in rats and rabbits (segment II), and prenatal and postnatal development in rats (segment III). In the embryo-fetal development study, we found that only mild maternal toxicities of ZYP were detected in rats at the dose of 24 g/kg/d and were limited to decreased extra-uterine weight gain and food intake, and there was no reproductive toxicology in rabbits even at the maximum administration dose [11]. The present preclinical study further reports the effects of ZYP on fertility and early embryonic development in male and female rats, which provides needed preclinical safety evidence to support its clinical usage.…”