الفهرس 
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Abstract
CRC is the most prevalent cancer worldwide, and its prevalence has been rising in
rearmost years. The incidence of CRC is thought to be linked to a number of variables.
According to epidemiological research, environmental variables, dietary habits, physical
activity, and hereditary factors all have a role in CRC.
DMH is a carcinogen furthermore an alkylating agent. DMH distresses several organs,
causing tumors, most notably in the colon, as well as clinical symptoms like ACF. The
investigation of DMH-induced colon carcinogenesis in mouse models sheds light on the
biochemical, molecular, and histological processes involved in the various phases of colon
carcinogenesis.
Nic is an FDA-approved anthelminthic pharmaceutical that is on the World Health
Organization’s (WHO) model list of essential medicines. Nic has been frequently found as a
major anti-cancer treatment in several high-throughput screenings.
The current study geared to inspect the potential protective consequence of Nic on DMHinduced
CRC in male albino mice through histopathological, immunohistochemical and
biochemical studies. To achieve this aim, the present study was designed. The histopathological
changes, AIF expression levels were assessed in the colons’ paraffin slides while MDA content,
TAC, and 8-OHdG levels were assessed in colon homogenate samples. The current study
embraced the subsequent groups: control, EDTA, DMSO, Nic (20 mg/kg), DMH (15 μg /g)
and protective groups. All treatments were done twice for 6 weeks.
The results of the present study could be summarized as the following:
Histopathological finding
a. H&E stain
In the colon sections of the mice in the control group, the glandular cells of the mucosal
layer retained a normal histological structure. In the lumen of colon sections from the induced
colon cancer group, tumor cells reflective of anaplasia, dysplasia, and hyperchromasia were
found. The mucosal lining epithelium got better markedly in the mice in the protected group.
b. Masson’s trichrome stain
The control group’s colon sections divulged a normal structure with collagenous fiber
content in the peri glandular cells of the mucosal layer and lamina propria. In the colon
sections of mice with induced colon cancer, however, leukocytic inflammatory cells
clustering with tumor cells was observed. The protective group’s structure was normal, with a
slight increase in collagenous content.
i. Immunohistochemical findings and image analysis results
The staining levels of AIF (% area) were significantly higher in DMH group (9.020 ±
1.686) than in the control group (2.396 ± 0.799). However, in the protective group (5.585 ±
1.719) AIF staining level was higher than in the control group.
ii. Biochemical parameters
a. MDA Content
The colon homogenates of mice treated with DMH (143.144 ± 40.302) were elevated
when compared to the control group (51.144 ±12.662). The protective group (82.567 ± 6.884)
treated with Nic and DMH prevented such an increment in LPO levels.
b. TAC
A significant reduction of colon TAC in both the DMH group (0.594 ± 0.194) and
protective group (0.844 ± 0.144) compared with the normal control group (1.182 ± 0.157).
c. 8-OHdG levels using ELISA technique
The DMH group (3.3708± 0.7737) had a considerable rise in 8-OHdG levels in the
colon compared to the control group (0.9925 ± 0.1038). The protective group (1.8563 ±
0.3106) treated with Nic and DMH hindered such an upsurge of 8-OHdG.
6.2. Conclusion
The current study found that Nic had a positive impact on CRC induced by DMH
injections. Nic’s effect on oxidative stress was achieved by reducing MDA levels and
increasing TAC. The reduced oxidative stress was reflected in the mucosa layer by decreasing
AIF staining intensity. As a result, Nic might be further developed as a strong CRC
preventive candidate remedy.
6.3. Recommendations
This study recommends the worth of Niclosamide use as an adjuvant drug in clinical
trials.