RT Journal Article
SR Electronic
T1 Alpha-tocopherol potentiates the cervical resistance decreasing effects of COX-inhibitors in pregnant rats: the putative role of cyclooxygenase-2 inhibition
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.118.251850
DO 10.1124/jpet.118.251850
A1 Anna Kothencz
A1 Judit Hajagos-Toth
A1 Kalman F. Szucs
A1 Annamaria Schaffer
A1 Robert Gaspar
YR 2018
UL http://jpet.aspetjournals.org/content/early/2018/11/15/jpet.118.251850.abstract
AB Vitamin E and their analogues as antioxidant and lipid soluble compounds can have diverse effects on the physiological processes. By binding to receptors and enzymes, they may modify the action of drugs. It has been proved that alpha-tocopherol succinate modifies the effects of β2 agonist terbutaline and cyclooxygenase (COX) inhibitors on rat trachea and myometrium. Our aim was to investigate how alpha-tocopherol and COX inhibitors may influence cervical resistance in rats. The cervical resistance of non-pregnant and 22-day-pregnant Sprague-Dawley rats was determined in an isolated organ bath in vitro. Alpha-tocopherol-succinate (10-7 M) was used, while the COX non-selective diclofenac (10-6 M), the COX-2 selective rofecoxib (10-6 M) and the COX-1 selective SC-560 (10-6 M) were applied as inhibitors. The COX activities of the cervices were measured by enzyme-immunoassay. The modifying effect of single doses of COX-inhibitors and tocopherol on the onset of labor was investigated in vivo. The cervical resistance of non-pregnant samples was not changed by either alpha-tocopherol or COX inhibitors. On pregnant cervices, tocopherol, diclofenac or rofecoxib pretreatment decreased cervical resistance that was further reduced by COX-inhibitors after pretreatment with tocopherol. Alpha-tocopherol elicited a significant COX-2 enzyme inhibition in pregnant cervical samples. By co-administration of tocopherol and rofecoxib, the parturition was initiated earlier than in the other groups. It is supposed that COXs play a significant role not only in cervical ripening, but also in the contraction of the cervical smooth muscle a few hours before parturition. This latter action may be developed by COX-2 liberated prostaglandins.