Abstract
BackgroundParaquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans. The consumption of phytochemical-rich plants can reduce the risk of chronic illnesses such as inflammation and neurodegenerative diseases. The present study aimed to investigate the protective effects of pomegranate seed extract (PSE) and juice (PJ) against PQ-induced neurotoxicity in mice.MethodsMice were assigned into 4 groups; three groups received PQ (10 mg/kg, i.p.) twice a week for 3 weeks. Two of the PQ-induced groups pretreated with either PSE or PJ. Detection of phytochemicals, total phenolics, and total flavonoids in PSE and PJ was performed. Tyrosine hydroxylase (TH) level was measured in the substantia nigra (SN) by Western blotting technique. Striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were detected using high-performance liquid chromatography (HPLC). The levels of adenosine triphosphate (ATP), malondialdehyde (MDA), and the activity of the antioxidant enzymes were estimated in the striatum by colorimetric analysis. Striatal pro-inflammatory and anti-inflammatory markers using enzyme-linked immunosorbent assay (ELISA) as well as DNA fragmentation degree by qualitative DNA fragmentation assay, were evaluated. Real-time polymerase chain reaction (qPCR) assay was performed for the detection of nuclear factor kappa B (NF-кB) gene expression. Moreover, Western blotting analysis was used for the estimation of the cluster of differentiation 11b (CD11b), transforming growth factor β (TGF-β), and glial cell-derived neurotrophic factor (GDNF) levels in the striatum.ResultsPretreatment with PSE or PJ increased the levels of TH in the SN as well as DA and its metabolite in the striatum that were reduced by PQ injection. PSE and PJ preadministration improved the PQ-induced oxidative stress via a significant reduction of the MDA level and the augmentation of antioxidant enzyme activities. PSE and PJ also significantly downregulated the striatal NF-кB gene expression, reduced the PQ-enhanced apoptosis, decreased the levels of; pro-inflammatory cytokines, CD11b, and TGF-β coupled with a significant increase of; interleukin-10 (IL-10), GDNF, and ATP levels as compared with PQ-treated mice.ConclusionsThe current study indicated that PSE and PJ consumption may exhibit protective effects against PQ-induced neurotoxicity in mice.
Highlights
Paraquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans
Various polyphenols were recorded such as propyl gallate, nobiletin, ellagic acid which is a polyphenolic–like hydrolyzable tannins, vitexin, and isovitexin that belong to the group of flavonoids
Polyphenolic compounds were recorded such as ellagic acid which is a polyphenolic–like hydrolyzable tannins as well as vitexin and isovitexin that belong to the group of flavonoids
Summary
Paraquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans. The consumption of phytochemical-rich plants can reduce the risk of chronic illnesses such as inflammation and neurodegenerative diseases. Parkinson’s disease (PD) is a chronic neurodegenerative disease [1], affecting mainly old people with enormous impacts on their life [2]. Dopaminiergic neuronal loss was observed to be associated with declined protein and activity levels of tyrosine hydroxylase (TH) [4]. It has been reported that DA is controlled by TH and it interacts with a-synuclein protein leading to the formation of intra-neuronal inclusions, named Lewy bodies (LBs) with consequent apoptosis [5]. LBs formation was associated with a movement impairment and a group of motor and non-motor symptoms [6]. The molecular pathogenesis of PD involves calcium release dysfunction, mitochondrial dysfunction, oxidative stress, and neuroinflammation [7]
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