Adedara_2024_Neurotoxicol__

The study investigated the protective effects of Hesperetin (HSP) and Hesperidin (HSD) on 1 methyl, 4 phenyl, 1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced Parkinsonism in Drosophila melanogaster (D. melanogaster). After a lifespan curve to choose exposure time and concentrations, flies were co-exposed to MPTP (0.4mg/g diet), Hesperetin (0.2 and 0.4mg/g diet), and Hesperidin (0.1 and 0.4mg/g) for 7 days. In addition to in vivo parameters, we assayed some markers of oxidative stress (lipid peroxidation, protein carbonylation, thiol content, hydrogen peroxide, and nitrate/nitrite levels, mRNA expression of Keap-1 (Kelch-like ECH associated protein 1)/Nrf2 (Nuclear factor erythroid 2 related factor 2), catalase (CAT), glutathione-S-transferase (GST) activities), and cholinergic (acetyl cholinesterase activity (AchE) and dopaminergic signaling (content and the mRNA expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO) activity). In addition to increasing the lifespan of flies per se, we found that both flavonoids counteracted the adverse effects of MPTP on survival, offspring emergence, and climbing ability of flies. Both flavonoids also reduced the oxidant damage on lipids and proteins and reestablished the basal levels of pro-oxidant species and activities of antioxidant enzymes in MPTP-flies. These responses were accompanied by the normalization of the mRNA expression of Keap1/Nrf2 disrupted in MPTP-flies. MPTP exposure also elicited changes in mRNA expression and content of TH as well as in MAO and AchE activity, which were reversed by HST and HSD. By efficiently hindering the oxidative stress in MPTP-flies, our findings support the promising role of Hesperetin and Hesperidin as adjuvant therapy to manage Parkinsonism.