Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Objective(s): This study aimed to investigate the effect of bee venom, a form of alternative therapy, on rotenone-induced Parkinson{u2032}s disease (PD) in mice. Moreover, the possible modulation by bee venom of the effect of Ldopa/ carbidopa, bromocriptine or rasagiline was examined; also the pharmacological pathways of the effect of bee venom on the nitric oxide pathway using nitric oxide synthase inhibitors and the effect of cholinergic blockade using atropine were tested. Materials and Methods: Rotenone (1.5 mg/kg, subcutaneously; s.c.) was administered every other day for two weeks and at the same time mice received the vehicle (DMSO, s.c.), bee venom (0.065, 0.13 and 0.26 mg/kg; intradermal; i.d.), L-dopa/carbidopa (25 mg/kg, intraperitoneal; i.p.), Ldopa/ carbidopa + bee venom (0.13 mg/kg, i.d.), bromocriptine (1.5mg/kg mice, i.p.), bromocriptine (1.5mg/kg mice, i.p.) + bee venom (0.13 mg/kg, i.d.), rasagiline (1 mg/kg, i.p.), rasagiline + bee venom (0.13 mg/kg, i.d.), LNAME (10mg/kg mice, i.p.) + bee venom (0.13mg/kg, i.d.), 7-nitroindazole (10 mg/kg mice, i.p.) + bee venom (0.13mg/kg, i.d.) and atropine (1mg/kg mice, i.p.) + bee venom (0.13mg/kg, i.d.). Then, wire hanging and staircase tests were performed and mice were euthanized and brains{u2032} striata separated. Oxidative stress biomarkers namely, malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), paraoxonase-1 (PON-1) and total antioxidant capacity (TAC) were measured. Additionally, butyrylcholinesterase (BuChE), monocyte chemoattractant protein-1 (MCP- 1), tumor necrosis factor-alpha (TNF-Ü) and dopamine (DA) were evaluated. Brain histopathological changes and caspase-3- expression were examined Results: Bee venom significantly enhanced motor performance and inhibited rotenone-induced oxidative/nitrosative stress, observed as a reduction in both MDA and NO along with increasing GSH, PON-1, and TAC. Besides, bee venom decreased MCP-1, TNF-Ü and caspase-3 expression together with an increase in BuChE activity and DA content

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