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Alpha-tocopherol succinate increases cyclooxygenase-2 activity: Tissue-specific action in pregnant rat uterus in
Anna Kothencz1, Judit Hajagos-Tóth1, Adrienn Csányi1
1Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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 (10-9-10-5M) and rofecoxib (10-10-10-5M) decreased the contractions in non-pregnant and 22-day-pregnant uteri. Tocopherol (10-7M) increased the relaxant effect only in pregnant uteri. Both diclofenac (10-9-10-5M) and rofecoxib (10-10-10-5M) reduced the tracheal tones, while they were slightly intensified by pretreatment with tocopherol (10-7M). Tocopherol enhanced the contractions of pregnant uteri. Tocopherol (10-7M) 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.
