Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1

• Published in: Acta parasitologica 2018-03, Vol.63 (1), p.198-209
• Main Authors: Salim, Elsayed I., Harras, Samar F., Abdalla, Aisha G., Mona, Mohmmed H.
• Format: Article
• Language: English
• Subjects: 1,2-Dimethylhydrazine; Aberration; ACF; Animal Systematics/Taxonomy/Biogeography; Animals; Antineoplastic Agents - administration & dosage; Antioxidants; Biomarkers; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Bryostatin-1; Bryostatins - administration & dosage; Carcinogenesis; Carcinogens; Caspase; Caspase-3; Catalase; Chronic infection; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - pathology; Colorectal Neoplasms - physiopathology; Cyclooxygenase-2; Disease Models, Animal; DMH; Ecology; Epithelium; Gene Expression; Glutathione; IgG; IgM; Immunity; Immunoglobulin G; Immunoglobulin M; Immunohistochemistry; Infections; Inhibition; Ki67; Lipid peroxidation; Medical Microbiology; Microbiology; Mucosa; Nitric oxide; Oxidation; Oxidative Stress; Oxyuriasis - complications; Oxyuriasis - parasitology; Oxyuroidea - physiology; Parasites; Parasitology; Peroxidation; Rat; Rats; Rodents; ROS; Serum levels; Superoxide dismutase; Syphacia muris; Treatment Outcome
• ISSN: 1230-2821; 1896-1851
• DOI: 10.1515/ap-2018-0023

Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina , was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S. muris infection combined with DMH has significantly increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1 after infection has significantly reduced the ACF numbers particularly larger ones. This inhibition was concomitant with significant inhibition in the immunohisto-chemical levels of the ki67, Caspase-3 and IgM levels in colorectal epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers levels of superoxide dismutase and catalase as well as the non-enzymatic antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis has significantly modulated the oxidative stress markers in the colorectum, while treatment with Bryostatin-1 has exerted significant curative potential. A mechanism could be explained that Bryostatin-1 treatment has reduced oxidative stress markers activities along with affecting host to parasite immunity possibly leading to changes in the COX-2 and APC expression, retarding cellular proliferation and subsequently reducing the colorectal carcinogenesis events.