Polychlorinated Biphenyl (PCBs)-Induced Oxidative Stress Plays a Critical Role on Cerebellar Dopaminergic Receptor Expression: Ameliorative Role of Quercetin

Abstract

Polychlorinated biphenyls (PCBs) exposure produces profound damage to the developing as well as adult central nervous system. Locomotor activities which are closely linked to dopaminergic neurotransmission are often impaired in PCBs toxicity. Targeting PCBs-induced oxidative stress using natural antioxidants is an attractive approach. Quercetin, a flavonoid is a safe and potent neuroprotective antioxidant. In this study, we sought to examine the protective role of quercetin against PCBs-induced neurodegeneration and dysfunction of dopaminergic receptors in the cerebellar region of adult male rats. They were divided into four groups. Group I received only vehicle (corn oil) intraperitoneally (i.p); Group II received Aroclor 1254 at a dose of 2 mg/kg bwt/day (i.p); Group III received Aroclor 1254 (i.p) and simultaneously quercetin (50 mg/kg bwt/day) through gavage; Group IV received quercetin alone (gavage). After 30 days treatment, rats were euthanized. The cerebellum was dissected from each rat brain, the levels of hydrogen peroxide, lipid peroxidation, protein carbonyl content, and activities of creatine kinase, acetylcholine esterase, membrane-bound ATPases were evaluated. Expressions of dopaminergic receptors and tyrosine hydroxylase in cerebellum were studied by semi-quantitative RT-PCR and western blot analysis, respectively. The PCBs-induced neurodegeneration was assessed by histological studies. Results proclaim that PCBs disturb dopaminergic receptors and also causes neurodegeneration in cerebellum via production of ROS. Simultaneous quercetin treatment had scavenged the free radicals induced by PCBs and protected dopaminergic receptors dysfunction in rat cerebellum.

Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)—Exposed Adult Male Rats

“…Previous studies in our laboratory suggests that PCBs induces oxidative stress leading to neuronal apoptosis and alternative death pathways [31], disrupts dopaminergic system and calcium homeostatsis in cerebral cortex and cerebellum of rats [32,33]. Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and impaires the neurochemical manifestations of the NMDA receptor-mediated intracellular signaling in the hippocampus [28].…”

“…Earlier studies in our laboratory reported that PCBs exposure impairs tight junctional proteins [31] and causes disruption of dopaminergic system in cerebral cortex and cerebellum of rat via the production of reactive oxygen species (ROS) [32,33]. PCBs-induced ROS production leads to oxidative/ nitrosative stress and cell death through over-activation of NMDARs both in culture and in animal models [34].…”

Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats

“…Quercetin's major circulating compounds in plasma were identified as quercetin 3-O-glucuronide, 3′-Omethylquercetin 3-O-glucuronide, and quercetin 3′-O-sulfate [32]. Once quercetin metabolites reach the blood flow, they are able to transverse the blood-brain barrier and are subsequently accumulated in the brain [33], where they exert their biological effects on the cerebellum [21,34,35].…”

Molecular Docking Study of Neuroprotectiveplant-Derived Biomolecules in Parkinson’s Disease

“…It also inhibited LPS/IFN-ϒ induced p38 and STAT-1 phosphorylation [11]. However, Quercetin, improved behavioural function, suppressed oxidative stress, brain swelling, and cellular injury both in vitro and in vivo [12]. Although, Sesamol and Naringenin reversed both the rotenone/MPTP+-induced toxicity in PD rat model [4].…”