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.

The present investigation is aimed to evaluate the anticataractogenic potential of C-phycocyanin (C-PC), extracted and purified from Spirulina platensis. Enucleated rat lenses were maintained in vitro in Dulbecco's modified Eagle medium (DMEM). Group I contained DMEM, Group II and Group III contained 100 μM of sodium selenite, Group III was subdivided into three viz IIIa, IIIb, IIIc supplemented with 100, 150, 200 μg of C-PC respectively. In the in vivo study, on tenth day post partum: Group I rat pups received an intraperitoneal injection of saline, Group II, IIIa, IIIb, and IIIc rat pups received a subcutaneous injection of sodium selenite (19 μmol/kg bodyweight) Group IIIa, IIIb, IIIc also received an intraperitoneal injection of 100, 150, 200 mg/kg body weight of C-PC, respectively, from postpartum days 9-14. On termination of the experiment, the lenses from both in vitro and in vivo studies were subjected to morphological examination and subsequently processed to estimate the activities of antioxidant enzymes namely superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, levels of reduced glutathione and lipid peroxidation products. Sodium selenite-exposed, C-PC-treated rat lenses (Group IIIc), showed significant restoration of antioxidant enzyme activity (p < 0.05) when compared to their counterpart Group II. Group IIIc conserved the levels of GSH and lipid peroxidation products at near to normal levels as compared with Group II. Results conclude the possible role of C-PC in modulating the antioxidant enzyme status, thereby retarding sodium selenite-induced cataract incidence both in vitro and in vivo.

Age related cataract is the leading cause of blindness associated with accumulation of oxidative stress in the eye lens. The present investigation reveals the rational of the beneficial effects of the natural compound C-phycocyanin (C-PC) is beneficial when administered to rat pups to protect against the secondary effects of sodium selenite induced cataractogenesis. A single subcutaneous dose of sodium selenite (19 μmol/kg body weight) on the 10th day of postpartum is adequate to induce cataract in rat pups. Serum biochemical parameters, such as the level of electrolytes, mean activities of anti-oxidant enzymes i.e. superoxide dismutase, catalase and reduced glutathione were observed to be significantly altered during selenite induced cataractogenic process. Histopathological examination revealed signs of degradation of normal cell architecture in the liver, kidney and eye lens. Interestingly, the deleterious effects of sodium selenite toxicity were restored with the simultaneous treatment with C-PC. The results suggest that an administration of 200 mg/kg body weight of C-PC has the ability to prevent/alter the secondary changes reflected in the serum biochemical and histological modifications in rats exposed to sodium selenite. These results complement the beneficial role of C-PC of cyanobacterial origin as a efficacious anti-cataractogenic agent against sodium selenite toxicity.

The present study is aimed to evaluate the putative neuroprotective effect of quercetin on PCB induced impairment of dopaminergic receptor mRNA expression in cerebral cortex of adult male Wistar rats. Group I (control) received only vehicle (corn oil; 0.1 ml/kg bwt) intraperitoneally (i.p); Group II Aroclor 1254 at a dose of 2 mg/kg bwt/day (i.p); Group III (Aroclor 1254-exposed (i.p), quercetin treated gavage (50 mg/kg bwt/day); Group IV received quercetin alone (gavage). 24 h after the 30th day treatment rats were euthanized. From each rat cerebral cortex tissues was collected and analyzed for mean activities of creatine kinase, acetylcholine esterase, Na(+)/K(+), Ca(2+) and Mg(2+)ATPases, Hydrogen peroxide generation, protein carbonyl content and lipid peroxidation levels. The fates of the mRNA expression of dopaminergic receptors, Cacna1d on all the groups were studied by RT-PCR. Results evidenced that significant reduction of neurodegeneration in PCBs exposed rats treated with quercetin was ascertained suggesting, quercetin treatment precludes against PCB induced oxidative stress and protects dopaminergic receptor dysfunction in rat cerebral cortex.

The lens transparency depends on higher concentration of lens proteins and their interactions. α-Crystallin is one of the predominant lens proteins, responsible for proper structural and functional architecture of the lens microenvironment, and any alteration of which results in cataract formation. The R12C, R21L, R49C and R54C are the most significant and prevalent αA-crystallin congenital cataract-causing mutants worldwide. Protein-protein interaction, crucial for lens proper structure and function, was posited to be lost due to point mutation and the elucidation of which could shed light on the molecular basis of cataract. In this conjuncture, we report quartz crystal microbalance (QCM) as a warranted technique for real-time analysis of protein-protein interaction between the N-terminal mutants of αA-crystallin and αB-crystallin. The biophysical characteristics of the mutated proteins were determined by size-exclusion HPLC, far-UV circular dichroism and fluorescence studies. Far-UV circular dichroism spectral analysis displayed slight modifications in β-sheet of R54C mutant. Altered intrinsic tryptophan fluorescence and decreased bis-ANS fluorescence were observed in all the N-terminal mutations revealing the tertiary structural changes and decreased exposure of surface hydrophobicity. An emphatic fall in the chaperone activity was observed in the N-terminal mutants, R12C, R21L and R54C. QCM analysis revealed the occurrence of strong heterogeneous interaction between αA-crystallin and αB-crystallin. Nevertheless, decreased interactions were observed with the N-terminal mutants. In summary, the present study concludes that the loss of interactions between αA-crystallin N-terminal mutants and αB-crystallin signifies quaternary structural alterations due to mutation in the arginine residues.