Study of possible effects of hormonal therapy on experimentally induced colitis in rats

ABSTRACT

Both beneficial and detrimental effects have been ascribed to sex steroids. In relation to gut inflammation, data is relatively limited. This study was designed to examine the influence of hormonal environment on severity of mucosal injury, level of interleukin 10 and oxidative stress in experimental colitis in ovariectomized rats. Sixty female albino rats were used in this work; 40 rats were bilaterally ovariectomized [Ovx] and 2 weeks thereafter; colitis was induced by intra-colonic administration of 2ml 3% acetic acid. Ten rats were sham-operated and served as a control normal group. The remaining 10 rats underwent colitis only and served as acetic acid-induced [AAI] colitis control untreated group. The Ovx rats were randomly divided into 4 groups [n=10 each] as follows Ovx-AAI colitis, estrogen-, progesterone- and tamoxifen- treated Ovx-AAI colitis. The colitis, Ovx-AAI colitis and tamoxifen groups showed grossly and microscopically evident colon mucosal injury [significantly increased ulcer score index], oedema [increased weight of distal colon], inflammatory cell infiltration, increased activity of myeloperoxidase enzyme [MPO], increased tissue malondialdehyde [MDA] and reduced glutathione [GSH] depletion compared to sham group. The Ovx-AAI colitis group showed more significant impairment in all the fore mentioned parameters as compared to the colitis group. The estrogen and progesterone treated Ovx-AAI colitis groups showed less impairment of all parameters used to assess colon mucosal injury, inflammatory response and oxidative stress compared to the non-treated counterpart. A significant decrease in the level of IL-10 was found in the colitis, Ovx-AAI colitis and Tamoxifen groups compared to sham operated group. The level of this cytokine in the estrogen and progesterone groups was comparable to that of the sham-operated group. Decline of IL-10 level may underlie the currently observed enhancement of colon inflammation and oxidative stress in female rats deprived from endogenous and exogenous female sex steroids. Estrogen and progesterone replacement therapy has been associated with restored level of this cytokine and decreased susceptibility to colon inflammation while the anti-estrogen analog tamoxifen lacks such effects