Studies on the mechanisms of abortion induction by Trichosanthin.
Radix trichosanthis, an abortifacient drug of mid-gestation, is extracted from the root tuber of Trichosanthes kirilowii Maxim, Cucurbitaceae. Its purified effective principle is a basic protein of molecular weight of approximately 18,000 and is named trichosanthin. By authorization it has been proved to be very effective in abortion induction of mid-gestation, particularly effective in curing ectopic pregnancy, hydatidiform mole, and invasive mole, and it has also some therapeutic action on choriocarcinoma. From the analysis of the experimental results on its initial site of action, the morphological and functional injury of trophoblast cells of placenta and of cultures in vitro and the effect on prostaglandin synthesis, the following conclusions are drawn concerning the mechanisms of abortion induction by trichosanthin: (1) Trichosanthin exerts its action directly on the placental trophoblasts and possesses a certain degree of specificity; (2) It selectively causes the necrotic denaturation of the syncytiotrophoblasts of placental villi, which makes fragments of the disintegrated cells clumped in the blood sinus, hence the coagulation of blood and the circulation hindrance, and tissue necrosis over large areas follows. The necrosis of placental villi is the primary response, and circulation hindrance secondary; (3) Structural injuries have been reflected on the impairment of functional activities; the concentrations of HCG and steroid hormones fall rapidly below the threshold values of threatened abortion. Serious structural and functional injuries bring about destructive disturbances on the normal endocrine relationship between the mother and the fetus and on metabolic exchanges. It is further postulated that through certain unknown mechanism the synthesis of prostaglandins increases, uterine contraction is initiated and abortion ensues. In summary, trichosanthin, a plant protein discovered from Chinese medicinal herbs, is a drug effective in abortion induction and against trophoblastic neoplasms. Preliminary elucidation of the mechanisms of abortion induction by trichosanthin has afforded a basis for the clinical application with better efficacy and its possible abortifacient use in early pregnancy and for the discovery of newer cancer chemotherapeutic agents.
D000019:Abortifacient Agents / Q000494:pharmacology*; D000020:Abortifacient Agents, Nonsteroidal / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000028:Abortion, Induced; D000818:Animals; D006063:Chorionic Gonadotropin / Q000097:blood; D002824:Chorionic Villi / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008516:Medicine, Chinese Traditional; D008518:Medicine, East Asian Traditional; D051379:Mice; D010920:Placenta / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D010940:Plant Proteins / Q000302:isolation & purification; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000188:drug therapy; D014327:Trophoblasts / Q000187:drug effects
D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D006063:Chorionic Gonadotropin; D010936:Plant Extracts; D010940:Plant Proteins