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 immunohistochemical 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.
Background: The fact that many laboratory rodent colonies were found to be parasite contaminated suggests a need for eradication to improve their quality for research and testing. However, the most anthelmintic are poisonous, and their application always entails some hazards to the host and interferes with the interpretation of the final results. The use of bryostatin as a potential anthelmintic drug is still a matter of controversy. Therefore, the present work was designed to examine the naturally extracted product bryostatin-1 from a marine bryozoan as a possible anthelmintic agent against Pinworms Syphacia muris. Results: Light and scanning electron microscopy revealed normal appearance of worms collected from the infected groups with S. muris and untreated by bryostatin-1, while those collected from the bryostatin-1 treated rats revealed drastic morphological changes in the mouth parts, anus, and cuticle of all treated worms. Significant effects of bryostatin-1 on Syphacia infection were also detected in rats regarding the final body weights, average food consumption, and organ weights. Moreover, the drug has also improved the serum biochemical changes significantly in the infected rats nearly to the normal levels. Conclusions: The study has provided morphological evidence of obvious effect of bryostatin-1 on the movement and feeding behavior of the parasite that lead to consequent weakness and death as well as improvement of the biochemical changes in the infected rats. The present study concluded that bryostatin-1 can be used as anthelmintic agent, although further studies are needed to insure the drug efficacy.
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