Abstract
The selection process for advanced therapies in patients with inflammatory bowel diseases (IBDs) must prioritize safety, especially when considering new biologic agents or oral molecule modulators. In C57BL/6 mice, oral infection with Toxoplasma gondii induces intestinal inflammation through excessive tumor necrosis factor (TNF) production, making TNF neutralization a potential therapeutic intervention. Considering this, the present study aimed to evaluate the therapeutic effects of BmooMP-α-I, a snake venom metalloprotease isolated from Bothrops moojeni, which could promote TNF hydrolysis, in treating T. gondii–induced ileitis. The results showed that C57BL/6 mice orally infected with 50 cysts of T. gondii from the Me49 strain and treated with BmooMP-α-I exhibited prolonged survival and improved morbidity scores. Additionally, the treatment ameliorated both the macroscopic and microscopic aspects of the intestine, reduced macrophage influx, and decreased the production of inflammatory mediators by mesenteric lymph node cells. These findings provide compelling experimental evidence supporting the ability of BmooMP-α-I to alleviate ileal inflammation. Considering that the currently available therapeutic protocols are not completely effective and often result in side effects, the exploration of alternative strategies involving novel therapeutic agents, as demonstrated in this study, has the potential to significantly enhance the quality of life for patients suffering from inflammatory bowel diseases.
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Acknowledgements
We acknowledge Vanessa Resende Souza Silva, Eliézer Lucas Pires Ramos, Zilda Mendonça, Ana Cláudia Pajuaba, and Marley Dantas for their technical support. Also, we would like to acknowledge the valuable assistance provided by ChatGPT, a language model developed by OpenAI, helping us to review this manuscript
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This study was financially supported by Brazilian research agencies (Fundação de Amparo à Pesquisa do Estado de Minas Gerais-FAPEMIG, Grant # RED-00013-14 and #APQ-01313-14; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) Grant # 311787/2013-4 and # 456650/2013-0; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES, Grant # AUXPE-02450/09-7).
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TS carried out the experiments, evaluated the data, and wrote the manuscript. CL, FF, and MF, helped with euthanasia of animals and experiments. HL aided in experiments and manuscript formatting. FF and NS helped with histological studies. FO and MS helped to obtain and purify the metalloprotease. TM collaborated to design the experiments and to evaluate the data. JM and CL supervised the study, analyzed the data, and helped to write the manuscript.
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Silva, T.L., Lopes, C.S., Silva, M.C. et al. Ileal inflammation is reduced due to treatment with a metalloprotease from BmooMP-α-I snake venom in an experimental model of Toxoplasma gondii infection. Parasitol Res 123, 65 (2024). https://doi.org/10.1007/s00436-023-08033-9
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DOI: https://doi.org/10.1007/s00436-023-08033-9