CATECHIN MITIGATES OXIDATIVE STRESS, NEUROINFLAMMATION, AND CONNECTOME DEGENERATION IN A Drosophila melanogaster MODEL OF VINCRISTINE-INDUCED NEUROTOXICITY

ABSTRACT Millions of people worldwide suffer from Parkinson’s disease, typified by death of dopaminergic neurons in the substantia nigra, which results in motor dysfunction and other crippling symptoms. Vincristine is an important substance in anticancer treatments, and misuse or prolonged use can lead to Parkinson’s disease symptoms. Catechin, being part of the flavonoid polyphenol group, has strong anti-inflammatory and antioxidant qualities and is usually added to diets and taken as a supplement. This study aims to evaluate the protective effects of catechin against vincristine-induced neurotoxicity in a Drosophila melanogaster model, with a specific focus on reducing oxidative stress, suppressing neuroinflammation, and preventing connectome degeneration. Three-day-old flies were split into 5 separate groups of thirty flies per group for 7 days. During the 7-day period of survival tests, the flies were given varying amounts of vincristine (1ml, 2ml, and 3ml/diet) and catechin (50, 100, 200 µM). The flies were therefore exposed to 200 µM catechin and 3ml of vincristine for another 7days. Neurobehavioral assays, including crawling, climbing, phototaxis, and chemotaxis, were assessed. Biochemical analyses, utilising nitric oxide and MDA as oxidative stress markers, were also conducted. Additionally, microanatomical studies using H&E were performed. In flies exposed to vincristine-induced toxicity, a significant elevation of oxidative stress and a decrease in antioxidant level was observed. When catechin was introduced, the result was reversed. Histologically, there was neurodegeneration and expression of pyknotic cells in vincristine-induced parkinsonism but when co-treated with catechin, the cells were preserved. These findings demonstrated catechin as a promising neuroprotective and neurodegenerative agent by ameliorating vincristine-induced Parkinsonism and by regenerating the pyknotic cells in the Drosophila melanogaster model.