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Resveratrol regulates Nrf2-mediated expression of antioxidant and xenobiotic metabolizing enzymes in pesticides-induced Parkinsonism.
Protein Pept Lett. 2020 Apr 03 [Online ahead of print]PP

Abstract

BACKGROUND

Combined maneb (MB) and paraquat (PQ), two widely used pesticides, increases oxidative stress leading to Parkinsonism. Xenobiotic metabolizing enzymes, cytochrome P450 (CYP) 2D6 and its mouse ortholog Cyp2d22 protect against Parkinsonism. Resveratrol, an antioxidant, restores antioxidant defense system through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). However, a crosstalk between Cyp2d22/CYP2D6-mediated protection and resveratrol-induced Nrf2 activation leading to neuroprotection is not yet elucidated.

OBJECTIVE

The study aimed to decipher the effect of resveratrol on Nrf2 activation and expression of its downstream mediators, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) and thioredoxin 1 (Trx1) along with Cyp2d22/CYP2D6 activity in combined MB and PQ mouse model of Parkinsonism and differentiated neuroblastoma cells.

RESULTS

MB and PQ reduced the dopamine content (mouse) and Cyp2d22/CYP2D6 activity (mouse/neuroblastoma cells) and increased the nuclear translocation of Nrf2 and expression of NQO1 and Trx1 (both). Resveratrol ameliorated pesticides-induced changes in dopamine content and Cyp2d22/CYP2D6 activity. It was found to promote nuclear translocation of Nrf2 and expression of NQO1 and Trx1 proteins. Since Cyp2d22/CYP2D6 inhibitor (ketoconazole/quinidine) per se reduced Cyp2d22/CYP2D6 activity and dopamine content, it was found to substantially increase the pesticides-induced reduction in Cyp2d22/CYP2D6 activity and dopamine content. Inhibitors normalized the pesticides induced changes in Nrf2 translocation and NQO1 and Trx1 levels in pesticides treated groups.

CONCLUSION

The results suggest that resveratrol promotes the catalytic activity of xenobiotic metabolizing enzyme, Cyp2d22/CYP2D6, which partially contributes to Nrf2 activation in pesticides-induced Parkinsonism.

Authors+Show Affiliations

Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh. India.Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh. India.Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-IITR, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh. India.Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh. India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32242774

Citation

Sami-Ur-Rasheed, Mohd, et al. "Resveratrol Regulates Nrf2-mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-induced Parkinsonism." Protein and Peptide Letters, 2020.
Sami-Ur-Rasheed M, Tripathi MK, Patel DK, et al. Resveratrol regulates Nrf2-mediated expression of antioxidant and xenobiotic metabolizing enzymes in pesticides-induced Parkinsonism. Protein Pept Lett. 2020.
Sami-Ur-Rasheed, M., Tripathi, M. K., Patel, D. K., & Singh, M. P. (2020). Resveratrol regulates Nrf2-mediated expression of antioxidant and xenobiotic metabolizing enzymes in pesticides-induced Parkinsonism. Protein and Peptide Letters. https://doi.org/10.2174/0929866527666200403110036
Sami-Ur-Rasheed M, et al. Resveratrol Regulates Nrf2-mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-induced Parkinsonism. Protein Pept Lett. 2020 Apr 3; PubMed PMID: 32242774.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol regulates Nrf2-mediated expression of antioxidant and xenobiotic metabolizing enzymes in pesticides-induced Parkinsonism. AU - Sami-Ur-Rasheed,Mohd, AU - Tripathi,Manish Kumar, AU - Patel,Devendra Kumar, AU - Singh,Mahendra Pratap, Y1 - 2020/04/03/ PY - 2019/12/31/received PY - 2020/02/14/revised PY - 2020/02/18/accepted PY - 2020/4/4/entrez KW - CYP2D6. KW - Cyp2d22 KW - MB KW - Nrf2 KW - PQ KW - resveratrol JF - Protein and peptide letters JO - Protein Pept. Lett. N2 - BACKGROUND: Combined maneb (MB) and paraquat (PQ), two widely used pesticides, increases oxidative stress leading to Parkinsonism. Xenobiotic metabolizing enzymes, cytochrome P450 (CYP) 2D6 and its mouse ortholog Cyp2d22 protect against Parkinsonism. Resveratrol, an antioxidant, restores antioxidant defense system through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). However, a crosstalk between Cyp2d22/CYP2D6-mediated protection and resveratrol-induced Nrf2 activation leading to neuroprotection is not yet elucidated. OBJECTIVE: The study aimed to decipher the effect of resveratrol on Nrf2 activation and expression of its downstream mediators, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) and thioredoxin 1 (Trx1) along with Cyp2d22/CYP2D6 activity in combined MB and PQ mouse model of Parkinsonism and differentiated neuroblastoma cells. RESULTS: MB and PQ reduced the dopamine content (mouse) and Cyp2d22/CYP2D6 activity (mouse/neuroblastoma cells) and increased the nuclear translocation of Nrf2 and expression of NQO1 and Trx1 (both). Resveratrol ameliorated pesticides-induced changes in dopamine content and Cyp2d22/CYP2D6 activity. It was found to promote nuclear translocation of Nrf2 and expression of NQO1 and Trx1 proteins. Since Cyp2d22/CYP2D6 inhibitor (ketoconazole/quinidine) per se reduced Cyp2d22/CYP2D6 activity and dopamine content, it was found to substantially increase the pesticides-induced reduction in Cyp2d22/CYP2D6 activity and dopamine content. Inhibitors normalized the pesticides induced changes in Nrf2 translocation and NQO1 and Trx1 levels in pesticides treated groups. CONCLUSION: The results suggest that resveratrol promotes the catalytic activity of xenobiotic metabolizing enzyme, Cyp2d22/CYP2D6, which partially contributes to Nrf2 activation in pesticides-induced Parkinsonism. SN - 1875-5305 UR - https://www.unboundmedicine.com/medline/citation/32242774/Resveratrol_regulates_Nrf2-mediated_expression_of_antioxidant_and_xenobiotic_metabolizing_enzymes_in_pesticides-induced_Parkinsonism L2 - http://www.eurekaselect.com/180694/article DB - PRIME DP - Unbound Medicine ER -
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