In vivo effects of Cisplatin and titanium dioxide nanoparticles combined treatment

Cisplatin, the first metal-based chemotherapeutic drug, remains widely used in treating various solid cancers despite its side effects and drug resistance. Researchers have explored combining Cisplatin with multiple substances to overcome its limitations. Different nanoparticles have been studied with Cisplatin. We examined the in vivo effects of orally administered Cisplatin (50 g/ml) and titanium dioxide nanoparticles (NPTiO2, 50 g/ml), both alone and in combination, in D. melanogaster. In this context, Drosophila melanogaster serves as a valuable alternative model for assessing the toxicity of many substances and diseases like cancer, Alzheimers, and alcoholism. We investigated whether co-exposure to cisplatin and NPTiO2 induces synergistic transcriptional repression in vivo. Using RNA-seq and bioinformatics analyses, we evaluated gene modulation to assess toxic effects in each experimental group. We found that flies treated with either cisplatin or NPTiO2 alone showed gene modulation associated with non-toxic substance processing. However, the group treated with both cisplatin and NPTiO2 showed a limited number of Differentially Expressed Genes (DEGs) and disruptions in cell division and DNA/RNA metabolism. Mortality rates remained statistically unchanged across all groups. These findings suggest that co-exposure to Cisplatin and NPTiO2 causes transcriptional repression and disruption of critical cellular pathways, indicating potential impairments in cellular function.