In able to attenuate extra-intestinal manifestations that were

In
the current study Sodium selenite (sod sel) effectively suppressed acetic
acid-induced colitis in rats which was comparable to mesalamine. This result is
maybe attributed to its anti-inflammatory and antioxidant properties that
indicated by attenuating weight loss, DAI, as well as macroscopic and
microscopic colonic damage. Furthermore, sod sel was able to attenuate extra-intestinal
manifestations that were revealed by restoring normal blood elements, kidney
function and liver biomarkers. 

Colonic
instillation of 4% acetic acid 
generated strong inflammatory
responses that characterized
by extensive ulceration, diarrhea, hematochezia and weight loss
that are similar to what arises in human UC  (Varshosaz et al., 2010) .Our
results showed increased fecal frequency; that
may be due to direct damaging effects of acetic acid as well as alterations in
epithelial function, either directly or indirectly by products arise from
activated mast cells (Stein et al., 1998).The body weight changes without any significant variation in
the food and water intake could be due to  GIT absorptive functions alterations (Stein et al., 1998). This was associated with
increase in colon mass index that may be interrelated to the submucosal edema appeared
histologically. A rise in the spleen index, a marker of inflammation (Cuzzocrea et al., 2003), was also noted in acetic acid
treated rats.  

Treatment
with sod sel significantly improved clinical symptoms, including diarrhea and
fecal occult blood, as well as restored the rate of weight gain and decreased
colon mass index and spleen index, in a manner comparable to mesalamine. This
was consistence with the study of Sang et al (Sang et al., 2016) who revealed that sodium selenite
improved colon shortening, body weight loss, disease activity index, and
histopathological score in mice with DSS-induced colitis

Intrarectal
administration of acetic acid produces acetate ions, which results in immense intracellular
acidification that damages epithelial cells that leads to  marked inflammatory response as evident by intense
inflammatory cells infiltrations into colonic tissues with
subsequent release of pro-inflammatory cytokines (Fabia et al., 1992, Kandhare et al., 2013). Consistently, the present study showed that administration of acetic acid caused extensive
macroscopic and microscopic damage of the colon with significant increases in
colonic MPO activity as well as in TNF-? and IL1ß expressions. sod sel
treatment was effective in reducing macroscopic damage score, total histology
score, MPO activity and the inflammatory cytokines expression.

It
was described that ROS (reactive oxygen species) produced in the inflamed
mucosa can moderate many inflammatory events. ROS produce numerous inflammatory
cytokines in different tissues which exacerbate tissue damage. In the present
investigation, acetic acid administration induced marked oxidative stress that
was associated with marked depletion of the cellular antioxidant, GSH as was
reported in earlier studies
(Nieto et al., 2000).

The
activities of the antioxidant enzymes such as SOD and catalase were also decreased
in colitis rats. This  have  been stated in experimental colitis in
previous study (Boots et al., 2008). The free radicals that occur during
oxidative damage attack polyunsaturated fatty acids in plasma membrane resulted
in membrane lipid peroxidation and severe cell damage. This action has a
significant role in the pathogenesis of the disease. In this study colitis
control animals showed increased MDA levels in colon tissue. Sod sel treatment significantly
reduced the elevated MDA levels. A significant reduction in MDA by treatment
with sod sel shows the anti-inflammatory effect in the experimental colitis
model and this could be associated with the antioxidant and free radical
scavenging ability of sod sel. GSH is considered an essential
intracellular antioxidant agent in mammalian GIT. It has a crucial role in the
repair mechanism of  mucosal damage caused
by free radicals. During inflammation, GSH level reduced that cause severe
degradation of colon mucosa. Therefore, GSH has a significant role in
protecting the intestinal cells and subsequently inflammation (Schreck et al., 1991). Treatment with sod sel significantly increased the colonic
GSH level that control macroscopic and histopathologic parameter.

Nitric
oxide (NO) is an essential proinflammatory mediator. That has been testified as
potential mediators for colitis (Whittle, 1997). The  higher interstitial edema, , fluid exudation
across intestinal capillaries, increased arteriolar blood flow, thickening of
the intestinal wall, are all related to inflammatory mediators like  NO (Whittle, 1997). The
present study showed that sod sel significantly repressed NO production that prohibited
peroxynitrite formation from inflammatory cells and ameliorating inflammation.

Ulcerative colitis has been related to a powerful local immune
response and recruitment of lymphocytes and macrophages followed by release of
soluble cytokines. Cytokines are important elements in gastrointestinal
inflammation,  and their overproduction
result in injurious events. TNF and IL1? are proinflammatory cytokines arise
from the macrophages and lymphocytes in the early inflammatory response (Fuss et al., 1996). in
our experiment TNF and IL1? where increased after acetic acid instillation. Sod
sel treatment inhibits TNF and IL1? which may be due to inhibition of their
synthesis or release.

Previous studies have connected selenium with diminishing
inflammation, Gazdik  et al. (Gazdik et al., 2002) reported decreased consumption of
corticosteroids after Se supplementation in corticoid-dependent asthmatics.
There have been a study  showed  that there was a significant amelioration in
lung function in patients with Cystic Fibrosis with
selenium supplementation (Wood et al., 2003). In
a study of 46 patients with rheumatoid arthritis and 48 age-matched controls,
serum se levels were significantly reduced (Pemberton et al., 2009). 

Sodium
Selenite was shown to decrease the other inflammatory mediators levels in colon
tissue, as the intercellular adhesion molecule, ICAM-1, which aids  the recruitment of leukocytes, the initiation
and continuation of intestinal inflammation in IBD as well (Woywodt et al., 1999, Sun
et al., 2001, Li et al., 2005). Inhibition of ICAM-1 by sod sel was
previously shown by Zhang et al. (Zhang et al., 2002). However, sod sel was shown to
preserve of another adhesion molecule level, called junctional adhesion
molecule (JAM-a) which belongs to an immunoglobulin super family in tight
junctions of epithelial cells (Ebnet et al., 2003) and mainly involved in interactions
with ?2 integrins throughout the inflammatory responses, and it hinders the
synthesis of eicosanoids and oxidative DNA injury (Osakabe et al., 2004). This shows that the drug, by
increasing JAM-A, might decrease impairment of the epithelial barrier function
and the resulting intestinal inflammation.

In the current
study, oxidative stress was assessed in the erythrocytes. Erythrocytes (RBCs)
are exposed to oxidative stress more than other cells due to heme iron and
oxygen, that can produce superoxides, H2O2 and lipid
peroxides. The hydroperoxides themselves are not very reactive but are readily transformed
to hydroxyl and alkoxyl radicals in the presence of free iron and electron
donor molecules, which extensively impose damage on biomolecules. Therefore,
RBCs are believed to have a very effective defense mechanism against peroxides (Giulivi and Davies, 1990) that may explain depletion in RBCS
and hemoglobin in the present study which were restored in treated groups due
to antioxidant effect of sod sel.

The
generation of free radicals is considered to be the primary cause of the
hepatic and renal damages. These free radicals combined with the cellular lipid
and proteins which in turn, initiate lipid peroxidation process and protein
carbonylation, resulting in structural changes in bio-membranes, loss of
integrity, and damage of cellular membranes. Accordingly, serum transaminases
activities as well as urea and creatinine levels were increased in acetic acid
control rats. Treatment with sod sel was able to restore normal level of the
liver enzymes, urea and creatinine, probably due to its antioxidant properties.