Exposure to cytarabine causes side effects on adult development and physiology and induces intestinal damage via apoptosis in Drosophila

Cytarabine (Ara-C) is a widely used drug in acute myeloid leukemia (AML). However, it faces serious challenges in clinical application due to serious side effects such as gastrointestinal disorders and neurologic toxicities. Until now, the mechanism of Ara-C-induced damage is not clear. Here, we used Drosophila melanogaster (fruit fly) as the in vivo model to explore the side effects and mechanism of Ara-C. Our results showed that Ara-C supple-mentation delayed larval development, reduced lifespan, impaired locomotor capacity, and increased suscepti-bility to stress response in adult flies. In addition, Ara-C led to the intestinal morphological damage and ROS accumulation in the guts. Moreover, administration of Ara-C promoted gene expressions of Toll pathway, IMD pathway, and apoptotic pathway in the guts. These findings raise the prospects of using Drosophila as in vivo model to rapidly assess chemotherapy-mediated toxicity and efficiently screen the protective drugs.

Automated summary

Cytarabine (Ara-C) is commonly used for the treatment of acute myeloid leukemia (AML), but it faces challenges due to severe side effects. The mechanism of Ara-C-induced damage is unclear. This study used fruit flies as an in vivo model and found that Ara-C supplementation caused developmental delays, reduced lifespan, impaired locomotor capacity, and increased stress response. Ara-C also led to intestinal morphological damage and accumulation of reactive oxygen species (ROS). Furthermore, Ara-C administration promoted gene expressions related to Toll pathway, IMD pathway, and apoptotic pathway in the gut. These findings suggest that fruit flies can be a useful in vivo model for assessing chemotherapy toxicity and screening protective drugs efficiently.