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

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

Role of peroxisome proliferator activated receptor [PPAR] agonists in experimental liver fibrosis in rats

The ligand-dependent transcription factors, peroxisome proliferator-activated receptors [PPARs] are expressed in hepatic stellate cells [HSCs], which are the cells reported to play a central role in liver fibrosis. It has been reported that the transcriptional activity of PPAR gamma and alpha is reduced during activation of HSCs. The aim of the present study was to evaluate whether oral administration of pioglitazone [alpha PPAR gamma ligand], and bezafibrate [alpha PPAR alpha ligand], might retard liver fibrosis in rats. Fifty male albino rats weighing 150-200 g were used in the present study. Rats were divided into five groups, each often rats. Group I, injected intraperitonealy [i.p.] by thioacetamide [TAA]. Group II, injected i.p. by saline. Groups III and IV, treated with bezafibrate and pioglitazone respectively, orally starting from the first day of TAA administration. Group V, served as a control group for groups III and IV. The duration of the study was six weeks. Administration of TAA to rats for six weeks resulted in significant increases in portal pressure, serum cytokines [tumor necrosis factor-alpha TNF-alpha and transforming growth factor-beta 1 TGF-beta 1], hepatic hydroxyproline [HPO], and serum aspartate aminotransferase [AST] and alanine aminotransferase [ALT] associated with a significant decrease in hepatic glycogen concentration. On the other hand, the two PPAR ligands, pioglitazone and bezafibrate, produced a significant decrease in portal pressure, a significant decrease in serum TNF-alpha and TGF-beta 1, a significant improvement in all the estimated parameters of liver function, as well as a significant decrease in hepatic HPO concentration in rats that received the drugs for six weeks compared to the control untreated rats. The results of the present study demonstrated that the PPAR agonists, pioglitazone and bezafibrate were effective in preventing the fibrogenic process via modulating the action of the cytokines TNF-alpha and TGF- beta1. Further studies on humans are needed in order to assess the clinical use of PPAR agonists in patients with liver fibrosis