ABSTRACT
BACKGROUND: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide. METHODS: Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson's disease (PD) induced by rotenone in rats, and the findings were compared to our previous study on mice model. RESULTS: Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compared to the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats with regards to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding oxidative stress and energetic indices. CONCLUSION: Curcumin succeeded in attenuating the severe effects of Parkinson's disease in the rat model and can be considered as a potential dietary supplement. Adenosine A2AR antagonist has almost the same pattern of improvement as Sinemet® and may be considered as a promising therapy against PD. To compare the role of animal species in response to PD symptoms and treatments, our previous report on mice explored the response of mice to rotenone toxicity in comparison with rats, where rats have shown a higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.
Subject(s)
Curcumin , Neuroprotective Agents , Parkinson Disease , Parkinsonian Disorders , Adenosine , Aged , Animals , Curcumin/pharmacology , Disease Models, Animal , Dopamine Agonists , Humans , Inflammation Mediators , Mice , Neuroprotective Agents/pharmacology , Parkinson Disease/drug therapy , Parkinson Disease/etiology , Parkinson Disease/metabolism , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/drug therapy , Rats , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2A/metabolism , Rotenone/pharmacologyABSTRACT
Detoxification is one of the main vital tasks performed by the liver. The purpose of this study was to investigate whether mustard in its normal or nanoparticles could confer a protective/therapeutic effect against TAA-induced acute liver failure in experimental animal models. Mustard ethanolic extract was analyzed by HPLC/MS. To induce liver failure, male rats were injected with 350 mg/kg bw TAA IP, then treated orally with a dose of 100 mg/kg for 15 d of mustard extract and its nanoform before and following induction. The levels of serum liver functions, total cholesterol (TCHo), total glyceride (TG), total bilirubin (TBIL), hepatic malonaldhyde (MDA) and nitric oxide (NO),glutathione (GSH), sodium oxide dismutase (SOD), as well as tumor necrosis factor (TNF-α,) and interleukin 6 (IL-6), were estimated. DNA genotoxicity and hepatic pathology, and immunohistologic (IHC) changes were assayed. The antioxidant content of Phenolic acids, flavonoids in mustard ethanolic extract substantially decreased the levels of ALT, AST, ALP and rehabilitated the histopathological alterations. In addition, nanoforms of mustard ethanol extract have notably increased the levels of GSH, SOD and significantly reduced the levels of MDA. The expression levels of TNF-α and IL-6 in serum and tissue were markedly downregulated. DNA genotoxicity was significantly reversed. Mustard introduced a protective and medicinal effect against TAA in both its forms.
