Tenebrio molitor as a new alternative model for the investigation of chemotherapy-induced intestinal toxicity

Lara Luisa Valerio de Mello Braga , Gisele Simão , Carolina Silva Schiebel , Yasmin Felipichuki Oliveira , Liza Brandão da Rosa , Marcelo Biondaro Gois , Elizabeth Soares Fernandes , Daniele Maria-Ferreira
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Abstract

Alternative animal models have become increasingly necessary due to legal regulations aimed at reducing the use of laboratory animals. Invertebrates are gaining in importance and have been intensively researched in recent years due to their pathophysiological similarities with rodents. Among these organisms, Tenebrio molitor, also known as the yellow mealworm beetle, stands out. In this study, we investigated whether T. molitor could be an alternative for studying the toxicity of chemotherapeutic agents. For this purpose, T. molitor larvae were inoculated with irinotecan (IRI) or 5-fluorouracil (5-FU). Both chemotherapeutic agents increased the morbidity and mortality of T. molitor and led to an increase in total circulating cells. Glucose levels were decreased after treatment with 5-FU and alanine aminotransferase levels were decreased after IRI administration. Administration of IRI or 5-FU resulted in changes in the appearance, consistency and amount of T. molitor frass. Finally, both IRI and 5-FU promoted severe histologic damage in the midgut and increased melanin deposition in peripheral tissues. Finally, we succeeded in developing an alternative experimental model for evaluating the toxicity of IRI and 5-FU. This model exhibits significant features of toxicity and intestinal damage, making it suitable for translational research purposes. T. molitor proves to be a versatile model organism with numerous advantages for experimental studies and offers a viable alternative for acquiring and expanding knowledge in the field of toxicology and pharmacology.

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天牛作为研究化疗引起的肠道毒性的一种新的替代模型
由于旨在减少使用实验动物的法律规定,替代动物模型变得越来越有必要。由于无脊椎动物的病理生理与啮齿类动物相似,它们的重要性与日俱增,并在近年来得到了深入研究。在这些生物中,Tenebrio molitor(又称黄粉虫甲虫)脱颖而出。在这项研究中,我们探讨了褐甲虫是否可以作为研究化疗药物毒性的替代品。为此,我们给甲虫幼虫接种了伊立替康(IRI)或5-氟尿嘧啶(5-FU)。这两种化疗药物都会增加褐飞虱的发病率和死亡率,并导致循环细胞总数增加。使用 5-FU 治疗后,葡萄糖水平下降,使用 IRI 后,丙氨酸氨基转移酶水平下降。给予 IRI 或 5-FU 会导致 T. molitor 果渣的外观、稠度和数量发生变化。最后,IRI 和 5-FU 都会导致中肠组织学严重损伤,并增加外周组织的黑色素沉积。最后,我们成功地开发了另一种实验模型来评估 IRI 和 5-FU 的毒性。该模型表现出明显的毒性和肠道损伤特征,适合用于转化研究。事实证明,褐飞虱是一种用途广泛的模式生物,在实验研究方面具有诸多优势,为获取和扩展毒理学和药理学领域的知识提供了一种可行的替代方法。
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