RESUMO
OBJECTIVES: This study aimed to investigate the effect of bee venom, a form of alternative therapy, on rotenone-induced Parkinson's disease (PD) in mice. Moreover, the possible modulation by bee venom of the effect of L-dopa/carbidopa or rasagiline was examined. MATERIALS AND METHODS: Rotenone (1.5 mg/kg, subcutaneously; SC) was administered every other day for two weeks and at the same time mice received the vehicle (DMSO, SC), bee venom (0.065, 0.13, and 0.26 mg/kg; intradermal; ID), L-dopa/carbidopa (25 mg/kg, intraperitoneal; IP), L-dopa/carbidopa+bee venom (0.13 mg/kg, ID), rasagiline (1 mg/kg, IP) or rasagiline+bee venom (0.13 mg/kg, ID). Then, wire hanging and staircase tests were performed and mice were euthanized and brains' 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-α), and dopamine (DA) were evaluated. Brain histopathological changes and caspase-3- expression were done. 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-α, and caspase-3 expression together with an increase in BuChE activity and DA content. CONCLUSION: Bee venom alone or in combination with L-dopa/carbidopa or rasagiline alleviated neuronal degeneration compared with L-dopa/carbidopa or rasagiline treatment only. Bee venom via its antioxidant and cytokine reducing potentials might be of value either alone or as adjunctive therapy in the management of PD.
RESUMO
This study was designed to investigate if the impairment of learning and memory induced by acute administration of scopolamine (1.4 mg/kg ip) in rats is associated with altered brain oxidative stress status. The passive avoidance paradigm was used to assess retrieval memory of rats after scopolamine treatment. Following retrieval testing, biochemical assessments of malondialdehyde (MDA), glutathione peroxidase (GSHPx), glutathione (GSH), and superoxide dismutase (SOD) levels/activities as oxidative stress indices were performed. This study also investigated the effect of acute administration of Hypericum perforatum extract (4.0, 8.0, 12.0, and 25.0 mg/kg ip), containing flavonoids with documented antioxidant activity, on brain oxidative status of nai;ve rats treated with amnestic dose of scopolamine. Results showed that administration of 1.4 mg/kg of scopolamine impaired retrieval memory of rats and that such amnesia was associated with elevated MDA and reduced GSH brain levels. In nai;ve rats, which have not been exposed to conditioned fear, scopolamine administration also increased MDA and reduced GSH levels, although with an increase in brain GSHPx activity. Pretreatment of the animals with Hypericum extract (4, 8, and 12 mg/kg) resulted in an antioxidant effect through altering brain MDA, GSHPx, and/or GSH level/activity. Since oxidative stress is implicated in the pathophysiology of dementia, the findings of this study may substantiate the value of scopolamine-induced amnesia in rats as a valid animal model to screen for drugs with potential therapeutic benefit in dementia. Exposure of animals to conditioned fear may be suggested to impair the balance between the rate of lipid peroxidation and the activation of GSHPx as a compensatory antioxidant protective mechanism. It is also concluded that low doses of Hypericum extract, demonstrating antioxidant activity, may be of value for demented patients exhibiting elevated brain oxidative status. Since depression commonly coexists with dementia, Hypericum extract as a drug with documented antidepressant action may also be a better alternative than several other antidepressant medications that have not been evaluated to test their effect on brain oxidative status during amnesia.