Tocolytic and toxic activity of papaya seed extract on isolated rat uterus

Carica papaya L. seeds extracted with 80% ethanol (EEPS) caused concentration-dependent tocolysis of uterine strips isolated from gravid and non-gravid rats. Prostaglandin F-2alpha and oxytocin-induced contractions of the isolated rat uterus were also inhibited in a concentration-dependent fashion by EEPS. Recoveries of the uterine activity after EEPS-induced uterine quiescence were very weak. Higher concentration of EEPS caused prompt uterine quiescence, which was also significantly irreversible. Pre-incubation of the rat uterus in Ringer Locke solution containing 10 mg/ml of EEPS for 1 hour prior to suspension in tissue baths led to significant depression of the spontaneous and KCl (60 mM)-induced uterine contractions relative to the solvent control (P<0.05). Cross sections of EEPS-pretreated non-gravid rat uterus (stained with hematoxyline and eosin) examined under light microscope revealed degeneration of the endometrium and myometrium with obvious cytoplasmic vacuolation indicating that EEPS could have direct toxic effect on the uterine tissues. Previous workers have reported benzyl isothiocyanate (BITC) as the main bioactive and anthelmintic compound in different extracts of papaya seeds. Using electron impact ionization methods, the presence of BITC in EEPS was also shown in this study. Mass spectra of both EEPS and standard BITC showed a base peak of benzyl/tropylium ion at m/z 91 (indicative of an aromatic compound) and the molecular ion peak of BITC (m/z 149). Our earlier studies have demonstrated BITC-induced functional and morphological derangement of isolated uterus. We thus conclude that at high concentration, EEPS is capable of causing irreversible uterine tocolysis probably due to the damaging effect of BITC (its chief phytochemical) on the myometrium. (C) 2003 Elsevier Inc. All rights reserved.