ABSTRACT
Despite the fact that levodopa has proven its effectiveness in treating the symptoms of Parkinson's disease (PD), increasing concerns have emerged about its possible long-term toxic effects on dopamine (DA) neurons. The study investigated the possible ameliorative effect of virgin coconut oil against l-dopa- induced neurotoxicity in adult rats. A total number of 40 rats were divided into four groups. Briefly, the first served as control, the second was orally administered virgin coconut oil (1.42 mL/kg), the third group was administered a single daily dose of l-dopa/carbidopa (100/10 mg/kg/day, p.o) and the fourth group pre-treated with virgin coconut oil then administered a single daily dose of l-dopa/carbidopa. The different treatments were extended for 30 days. l-dopa treated group exhibited aggressive behavior and behavioral abnormalities in open field test compared to control group. In addition, l-dopa treatment caused significant increase in the levels of striatal dopamine and norepinephrine and their metabolites with concomitant decrease of serotonin and its metabolite. Moreover, l-dopa treatment increased histamine and GABA levels. In addition, l-dopa treatment induced oxidative stress and energy crisis. The histological and immunohistochemical studies showed that l-dopa caused a remarkable neurodegeneration and increased glial fibrillary acidic protein (GFAP) immunoexpression in the striatal area. Virgin coconut oil co-treatment significantly minimized the harmful effects of l-dopa. In conclusion, the present study revealed that virgin coconut oil provided a notable protection against l-dopa's untoward effects.
Subject(s)
Coconut Oil/administration & dosage , Corpus Striatum/drug effects , Levodopa/toxicity , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Animals , Behavior, Animal/drug effects , Carbidopa/toxicity , Corpus Striatum/metabolism , Corpus Striatum/pathology , Male , Neurons/metabolism , Neurons/pathology , Parkinson Disease/complications , Parkinson Disease/drug therapy , Rats, Sprague-DawleyABSTRACT
AIM: The aim of this study was to investigate the effect of three different hydrogen peroxide (H2 O2 ) levels on blood and liver oxidative status, energy metabolites, and gene expression in male albino rats at two time intervals (2 and 4 weeks). METHODS: A total of 32 rats were divided into four groups. The first group received tap water and served as control. The second group received low dose of hydrogen peroxide (H2 O2 ; 0.25%), The third group received medium dose of H2 O2 (0.5%) and the fourth group received high dose of H2 O2 (1%) in drinking water. RESULTS: Present data showed that medium and high dose increased oxidative stress markers, decreased cell energy, and decreased antioxidant enzyme gene expression (GPx and Nrf2) and its downstream in contrast low dose did not show significant effects. CONCLUSION: This study might indicate that hydrogen peroxide medium level is the best dose for redox model status.
Subject(s)
Energy Metabolism/drug effects , Gene Expression/drug effects , Hydrogen Peroxide/toxicity , Liver/drug effects , 8-Hydroxy-2'-Deoxyguanosine , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Biomarkers/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Hydrogen Peroxide/administration & dosage , Liver/enzymology , Liver/metabolism , Male , Malondialdehyde/metabolism , NF-E2-Related Factor 2/metabolism , Oxidation-Reduction , Oxidative Stress , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Time FactorsABSTRACT
Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use cause neurobiological side effects. The aim of the present study was to investigate the prophylactic effect exerted by daily administration of ellagic acid (EA) and rosmarinic acid (RA) on DOX-induced neurotoxicity in rats. Our data showed that DOX-induced significant elevation of brain malondialdehyde, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), caspase-3, and cholinesterase associated with significant reduction in reduced glutathione, monoamines namely serotonin, dopamine, as well as norepinephrine. Concomitant administration of EA (10 mg/kg/day, p.o. for 14 days) and/or RA (75 mg/kg/day, p.o. for 14 days) with DOX significantly mitigated the neural changes induced by DOX. Meanwhile, treatment ameliorated pro-inflammatory cytokines as TNF-α, iNOS, and attenuated oxidative stress biomarkers as well as brain monoamines. In conclusion, EA and RA can effectively protect against DOX-induced neurotoxicity, and the mechanisms underlying the neuroprotective effect are potentially associated with its antioxidant, anti-inflammatory, and antiapoptotic properties.
