Abstract
Chemotherapy is a conventional and extensively used method for cancer treatment. There is a growing burden on patients and society due to the adverse effects of chemotherapeutics, even though survival rates are improving. Oxaliplatin is a widely used platinum-based drug for colorectal cancer treatment. But the prolonged usage of these drugs is linked to neurotoxicity, which is considered as one of the dose-limiting adverse effects. Drosophila melanogaster is an ideal model organism due to its short generation time, low maintenance costs, and well-characterized genome and is extensively employed to investigate neurological disorders, DNA damage, oxidative stress, and apoptosis-like mechanisms are analogous to mammalian systems. We aimed to examine the toxic effects of Oxaliplatin using the lowest dose (20 µg/mL) and highest dose (200 µg/mL) below LC50 on Drosophila model in larva and both young and old age groups. We monitored the alterations in behavior, developmental cycle, and biochemical changes in both larva and adult flies. In adult flies, there was pharmacological toxicity by platinum-DNA adduct formation, gut cytoskeletal disruptions, and DNA damage. Reactive Oxygen Species accumulation and apoptosis were identified in the adult flies' gut and brain. In case of Drosophila larva, oxidative stress in the cerebral lobes and gut was accompanied by abnormalities in their crawling, righting, and cold tolerance behaviors. Quantitative PCR analysis revealed alterations in the mRNA levels of antioxidant genes and apoptotic gene according to age. Our results strive to understand the thorough toxicity of Oxaliplatin not described in earlier studies.
