Alpha-tocopherol succinate increases cyclooxygenase-2 activity: Tissue-specific action in pregnant rat uterus in vitro.

Aims: Lipid soluble vitamin E plays a role in several physiological mechanisms, however, the mechanism of this action is controversial. We investigated how tocopherol (α-tocopherol acid succinate) influences the effects of cyclooxygenase inhibitors (COXi) in the smooth muscles.

Main Methods: The contractility of the samples from 22-day-pregnant myometrium and non-pregnant myometrium and trachea was determined in an isolated organ bath in vitro. The activity of cyclooxygenase enzymes (COX) was also measured in the tissues.

Key Findings: Diclofenac (10-10M) and rofecoxib (10-10M) decreased the contractions in non-pregnant and 22-day-pregnant uteri. Tocopherol (10M) increased the relaxant effect only in pregnant uteri. Both diclofenac (10-10M) and rofecoxib (10-10M) reduced the tracheal tones, while they were slightly intensified by pretreatment with tocopherol (10M). Tocopherol enhanced the contractions of pregnant uteri. Tocopherol (10M) itself can induce the cyclooxygenase activity and shift the COX-1 and COX-2 ratio to COX-2. The lowest COX activity was found in non-pregnant uteri, while the highest one was in the trachea.

Significance: The COX enzymes, especially COX-2, play an important role in the contraction of pregnant uteri in rat. Tocopherol has a tissue specific COX-2 activity increasing effect in pregnant rat uterus but has no such action in non-pregnant uteri or tracheal tissue. Hereby, tocopherol may intensify selectively the uterine relaxing effect of COX-2 inhibitors in preterm contractions. However, tocopherol can enhance the contractile response of pregnant uterus that may increase the risk of premature contractions.