Study Of Rhubarb's Toxicity On The Uterus And Ovarian And Its Reversibility In Rats

Objectives To compare the toxicity strength and reversibility of RWD and RTA in rat uterus and ovaries, and to clarify toxicity of Rhubarb on the reproductive system if reversible, if the RTA is the main toxic component of rhubarb. To provide experimental evidence for the clinical application of rhubarb.Methods Ninety female SD rats were randomly divided into normal control group?NC?, RWD2.0g.kg^-1?crude drug? and RTA73 mg.kg^-1, 30 rats in each group,continuous ig to 60 days.Respectively, after the last administration 24 h, withdrawal 30 d and 60 d take 10 rats to determination of serum progesterone?P?, testosterone?T?, estradiol?E₂? hormone content; calculation of the ovary, uterus organ index;observe the organizational structure of the uterus and ovarian abnormalities by HE; determination of Bax and Bcl-2 in ovarian, uterine through immunohistochemistry.Results 1 The effect on the levels of hormone in rat serum: Comparison of E₂, P, T in different time periods of RWD group: It showed that the levels of E₂ and P were significant different in the groups of administration groups compared with NC?P<0.05 or P<0.01?; the E₂ and P in stop drug 30 d group, which was higher than that of administration group?P<0.05? and lower than that of NC?P<0.05 or P<0.01?; It showed a higher level of E₂ and P when stop drug 60 d group compared with administered 2.0g.kg^-1 for 60d?P<0.05?, no significant difference compared with that of the NC?P>0.05?. The T in different time periods of administration groups had no significant difference compared with the normal control group?P>0.05?. Comparison of E₂, P, T in different time periods of RTA group: Compared with NC group, the levels of E₂, P were lower when administered 73 mg.kg^-1for 60d?P<0.05 or P<0.01?; It showed that the levels of E₂ was no significant different?P>0.05?while that of P was higher when 30 days after withdrawal compared with administered 73 mg.kg^-1 for 60d?P<0.05?, while both them were lower than that of NC?P<0.05 or P<0.01?; The E₂, P in 60 days after withdrawal were higher than that in administered group while lower than that in NC?P<0.05?. The level of T in administered and 30 days after withdrawal was higher than that in NC group?P<0.05?; It showed that the level of T was lower administered 73 mg.kg^-1 for withdrawal 60 d, while there was significant difference with NC?P<0.05?. Compare the level of E₂, P, T in the RWD and RTA groups at the same time: administration RTA group and withdrawal group, E₂ and P levels were lower than that in RWD group?P<0.05?. The level of T in administered RTA 73 mg.kg^-1 for 60 d was higher than that was administered RWD2.0g.kg^-1 for 60d?P<0.05?.2 The effect on the index of the ovary and uterus: Comparison of uterine and ovary index in different periods of RWD group: The uterus and ovary index in rat is lower than NC when administered 2.0g.kg^-1for 60d?P<0.05 or P<0.01?; 30 days after treatment group was higher than the administered 60 days group, lower than that of NC?P<0.05?; 60 days after treatment group wars higher than the administered 60 days group?P<0.05?, there was no significant difference with NC?P>0.05?. Comparison of uterine and ovary index in different time periods of RTA group: The administration of 60 d group was lower than that of NC?P<0.05 or P<0.01?; stop drug 30 d group wars higher than the administered 60 days group, lower than that of NC?P<0.05 or P<0.01?; stop drug 60 d group was higher than the administered 60 days group, lower than that of NC?P<0.05?. Comparison of uterine and ovary index in the same time periods of RTA group and RWD group: in the drug group, withdrawal group RTA were lower than RWD?P<0.05?. 3 The effect on the levels of expression of Bcl-2 in ovary and uterus of rats: the expression of Bcl-2 decreased when administered RWD 2.0g.kg^-1 for 60 dcompared with NC group?P<0.05 or P<0.01?; it increased compared with administered group, while compared with NC that is decreased when stop drug 30d?P<0.05 or P<0.01?; it increased when stop drug 60 d than administered 60d?P<0.05?, had no significant difference compared with the normal control group?P>0.05?. the level of expression of Bcl-2 of the administered RTA 60 d group showed a downward trend compared with the NC?P<0.05 or P<0.01?; it was higher in uterus when stop drug 30 d than administered 2.0g.kg^-1?P<0.05?, no significant difference in ovary compared with that of the administered group?P>0.05?. It decreased in ovary and uterus when stop drug 30 d than NC?P<0.05 or P<0.01?, and it was higher in the group stop drug 60 d of compared with the group of 73 mg.kg^-1, while lower than NC?P<0.05 or P<0.01?. The comparision of effect on the expression of Bcl-2 in the ovary and uterus in the groups of RWD and RTA at the same period: the level of Bcl-2 were both lower of the drug delivery group and the stopping drug group in RTA groups than that of RWD. 4 The effect on the expressions of the bax in the ovary and uterus in the rats: the expressions of Bax were significant different in the groups of RWD2.0g.kg^-1 compared with NC?P<0.05 or P<0.01?; withdrawal 30 d group was lower than that of 60 d group?P<0.05?, there was no significant difference in comparison with NC?P>0.05?; the result for stop drug 60 d group is the same above. Comparison of Bax level in RTA group in different time periods: the expressions of Bax were significantly different in the groups of RTA73 mg.kg^-1 compared with NC?P<0.05 or P<0.01?; withdrawal 30 d group was lower than that of 60 d group and higher than that of NC?P<0.05 or P<0.01?; withdrawal 60 d group was lower than that of 60 d group?P<0.05?, there was no significant difference compared with NC?P>0.05?. The effect on the expressions of Bax in the ovary and uterus in the groups of RWD and RTA in the same period: in the administration group and withdrawal 30 d group the expressions of Bax in the ovary and uterus RTA were higher than RWD?P<0.05?, in withdrawal 60 d group the level of Bax there was no significant difference comparison between RTA and RWD?P>0.05?.Conclusions Administrate RWD and RTA on the rat uterus, ovaries have significant toxicity,which is RTA heavier than RWD. Explanation that RTA was the main toxic effects of rhubarb site. The influence on the uterus and ovary induced by RWD that can returned to normal discontinued 60 days, the damage of RTA has yet to be fully back to normal, the damage of both them was reversible.