Effect of taurine in animals with colon cancer induced by chemicals and treated with 5-Fluoruracil

Abstract

Colorectal cancer (CCR) is one of the 10 most cancers worldwide, causing almost 10 million deaths in 2018. In Brazil, it is the third most incident cancer in men and the second, in women, reaching more than 16 thousand deaths in 2018. In the last 3 years it has been observed about 10% increase in mortality caused by CCR, demonstrating that the existing treatments are not totally effective (inefficacy, toxicity or non-adherence). The therapy consists of surgical removal and in some cases, adjuvant chemotherapy such as 5-fluorouracil (5-FU), and other associated drugs. The 5-FU, although widely used, causes several adverse effects related to renal, cardiac, hepatic toxicity and mucositis, as well as cases of resistance to therapy. Taurine is a semi-essential amino acid with potent antioxidant, anti-mutagenic and anti-inflammatory activity, inhibitor of TNF-alpha and NF-kB, capable of promoting cardiac and renal protection against tissue toxicity caused by chemotherapeutics such as doxorubicin and cisplatin. Studies suggest that its deficiency is associated with some types of neoplasia, such as breast cancer. We hypothesized that TAU may have a beneficial effect in reducing the adverse effects of 5FU, perhaps enhancing chemotherapeutic activity. In this context, the present aims to study the effect of TAU and 5FU on the chemical carcinogenesis model induced by 1,2-dimethylhydrazine in animals. After treatment, the organs (colon, liver, kidney, heart and spleen) will be analyzed histologically. In the colon will be checked the quantity, volume and distribution of lesions, besides the analysis of aberrant crypts, adenomas, adenocarcinomas, evaluation of local inflammatory process and dysplasia. The results of this phase of the project, if positive, will be used for further clinical research in patients. (AU)