Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos

Abstract

Colon cancer is one of the most prevalent neoplasms globally, with high mortality rates. Therefore, there is a constant search for alternative treatment and prevention measures. Some scientific studies have shown a high anticarcinogenic potential in natural and synthetic chemical substances, such as botryosphaeran, a fungal exopolysaccharide produced by Botryosphaeria rhodina MAMB-05. Botryosphaeran has demonstrated anticarcinogenic effects through immunomodulatory, cytotoxic and antioxidant activities. However, no scientific studies have been found related to the antitumor effects of botryosphaeran on colon cancer, and there is a need to investigate its potential antiproliferative activities in experimental models of colon carcinogenesis. Thus, the present study aimed to evaluate the chemoprotective capacity of botryosphaeran on initiation of 1,2-dimethyldrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Animals were divided into three groups: positive control (PC), negative control (NC) and botryosphaeran test (BT). PC group received subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week; NC group received similar subcutaneous injections of EDTA solution (DMH vehicle); BT group received daily doses of botryosphaeran (30 mg/kg b.w.) via gavage for 4 weeks and subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week. On the 13th week, animals were euthanized by anesthetic deepening and colon, kidney and liver were collected. We evaluated the evolution of body weight, food and water intake, absolute and relative weight of liver and kidneys, development of aberrant crypt foci (ACFs) and mucindepleted foci (MDFs), and the rates of mitosis, apoptosis and inflammatory infiltrate in histological sections stained with hematoxylin-eosin (HE). Statistical analysis was performed using one-way variance analysis (ANOVA) followed by Tukey’s test. Differences were considered significant when p < 0.05. Botryosphaeran caused no changes in food and water intake and showed no toxicity. However, the animals showed a significant reduction in weight gain during the first 4 weeks of treatment, which may be related to different mechanisms of action of botryosphaeran on body weight control. Botryosphaeran significantly reduced the development of ACs, ACFs and MDFs, demonstrating an important antioxidant activity, and significantly reduced the rates of inflammatory infiltrate in the animals’ distal colon, evidencing their immunomodulatory activity. There were no significant differences in the rates of apoptosis and mitosis in the colon, and the method of analysis may have influenced these results. In conclusion, botryosphaeran demonstrated a potential chemopreventive activity on the development of colon cancer, standing out as a possible therapeutic agent. However, further investigations are necessary to explore its exact mechanisms of action.