Anti-inflammatory effects and changes in prostaglandin patterns induced by 7β-hydroxy-epiandrosterone in rats with colitis

High dose levels of dehydroepiandrosterone and its 7-hydroxylated derivatives have been shown to reduce oxidative stress and inflammatory responses in dextran sodium sulfate (DSS)-induced colitis in rats. Another endogenous steroid, 7β-hydroxy-epiandrosterone (7β-hydroxy-EpiA) has been shown to exert neuroprotective effects at much smaller doses. Our aims were to evaluate whether 7β-hydroxy-EpiA pre-treatment prevents DSS-induced colitis and to determine whether the effects involve changes in anti-inflammatory prostaglandin (PG) D2 and 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) levels. Rats were administered 0.01, 0.1 and 1 mg/kg 7β-hydroxy-EpiA i.p. once a day for 7 days. Thereafter, colitis was induced by administration of 5% DSS in drinking water for 7 days. Levels of the PGs and the expression of cyclooxygenase (COX-2) and PG synthases were assessed during the course of the experiment. Administration of 7β-hydroxy-EpiA caused a transient increase in COX-2 and PGE synthase expression within 6–15 h and augmented colonic tissue levels of 15d-PGJ2 levels starting at day 2. Treatment with DSS resulted in shortened colon length, depleted mucus in goblet cells and induced oxidative stress. COX-2 and mPGES-1 synthase expression were enhanced and accompanied by increased PGE2, D2 and 15d-PGJ2 production. Although all dose levels of 7β-hydroxy-EpiA reduced PGE2 production, only the lowest dose (0.01 mg/kg) of the steroid completely prevented colitis damage and tissue inflammation. 7β-Hydroxy-EpiA pre-treatment prevents the occurrence of DSS-induced colitis through a shift from PGE2 to PGD2 production, associated with an early but transient increase in COX-2 expression and a sustained increase in the production of the anti-inflammatory prostaglandin 15d-PGJ2.