Impact of Levodopa and Black Pepper Essential Oil in a Zebrafish Model of Rotenone-Induced Parkinson Disease

Parkinson's disease, the second most common neurodegenerative disease, affects approximately 2 to 3% of individuals over the age of 65. It is characterized by the irreversible degeneration of cells in the central nervous system, compromising motor, physiological, and cognitive functions. The standard treatment is levodopa, a precursor of dopamine, whose prolonged use can cause motor complications, such as dyskinesia. Therefore, it is essential to develop alternative therapies that allow the dose of levodopa to be reduced without losing its efficacy, minimizing side effects. The present study evaluated the protective effect and toxicity of L-dopamine and Piper nigrum essential oil and their mixture in zebrafish embryos and larvae exposed to rotenone as an experimental model for Parkinson's-like disease. Parameters such as survival, hatching rate, teratogenicity, morphometry and behavioral tests (thigmotaxis, touch sensitivity, and optomotor response) were evaluated to investigate whether L-dopamine and Piper nigrum essential oil cause toxicity or can act as protective agents against the effects induced by rotenone, a highly toxic pesticide that causes behavioral alterations similar to symptoms of Parkinson's disease. Exposure to L-dopamine also resulted in defects in embryonic-larval development and behavioral alterations, showing a limited protective effect against toxicity induced by rotenone. On the other hand, Piper nigrum affected embryonic-larval development but showed no significant impact on zebrafish behavior. Furthermore, Piper nigrum showed no protective effect against defects induced by rotenone. It was concluded that rotenone is a chemical that induces phenotypes similar to Parkinson's disease in the zebrafish model. However, L-dopamine and Piper nigrum proved to be ineffective therapeutic alternatives to treat these symptoms in this model, presenting some toxic and synergistic effects. Thus, we emphasize the need to continue research in search of therapeutic approaches that can mitigate the effects of the disease induced by toxic agents such as rotenone in animal models.