A-tocopherol potentiates the cervical resistance decreasing effects of COX inhibitors in pregnant rats: The putative role of cyclooxygenase-2 inhibition

Abstract

Vitamin E and their analogs as antioxidant and lipid-soluble compounds can have diverse effects on the physiologic processes. By binding to receptors and enzymes, they may modify the action of drugs. It has been proved that a-tocopherol succinate modifies the effects of b2 agonist terbutaline and cyclooxygenase (COX) inhibitors on rat trachea and myometrium. Our aim was to investigate how a-tocopherol and COX inhibitors may influence cervical resistance in rats. The cervical resistance of nonpregnant and 22 day–pregnant Sprague-Dawley rats was determined in an isolated organ bath in vitro. a-Tocopherol-succinate (1027 M) was used, whereas the COX-nonselective diclofenac (1026 M), the COX-2–selective rofecoxib (1026 M), and the COX-1–selective SC-560 (1026 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 nonpregnant samples was not changed by either a-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. a-Tocopherol elicited a significant COX-2 enzyme inhibition in cervical samples from pregnant rats. By coadministration 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.