PMID- 32242774
OWN - NLM
STAT- MEDLINE
DCOM- 20210128
LR  - 20210128
IS  - 1875-5305 (Electronic)
IS  - 0929-8665 (Linking)
VI  - 27
IP  - 10
DP  - 2020
TI  - Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic 
      Metabolizing Enzymes in Pesticides-Induced Parkinsonism.
PG  - 1038-1045
LID - 10.2174/0929866527666200403110036 [doi]
AB  - 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.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Rasheed, Mohd Sami Ur
AU  - Rasheed MSU
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Lucknow 226 001, Uttar Pradesh, India
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
FAU - Tripathi, Manish Kumar
AU  - Tripathi MK
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Lucknow 226 001, Uttar Pradesh, India
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
FAU - Patel, Devendra Kumar
AU  - Patel DK
AD  - Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian 
      Institute of Toxicology Research (CSIR-IITR), Lucknow 226 001, Uttar Pradesh, 
      India
FAU - Singh, Mahendra Pratap
AU  - Singh MP
AD  - Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and 
      Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research 
      (CSIR-IITR), Lucknow 226 001, Uttar Pradesh, India
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Protein Pept Lett
JT  - Protein and peptide letters
JID - 9441434
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Pesticides)
RN  - 0 (Txn1 protein, mouse)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 1.14.14.1 (Cyp2d22 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 2)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (Nqo1 protein, mouse)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Cell Line, Tumor
MH  - Cytochrome P450 Family 2/*biosynthesis
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Male
MH  - Mice
MH  - NAD(P)H Dehydrogenase (Quinone)
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Neuroprotection/*drug effects
MH  - *Parkinson Disease, Secondary/chemically induced/metabolism/prevention & control
MH  - Pesticides/*toxicity
MH  - Resveratrol/*pharmacology
MH  - Thioredoxins/biosynthesis
OTO - NOTNLM
OT  - CYP2D6
OT  - Combined maneb (MB)
OT  - Cyp2d22
OT  - Nrf2
OT  - paraquat (PQ)
OT  - resveratrol
EDAT- 2020/04/04 06:00
MHDA- 2021/01/29 06:00
CRDT- 2020/04/04 06:00
PHST- 2019/12/31 00:00 [received]
PHST- 2020/02/14 00:00 [revised]
PHST- 2020/02/18 00:00 [accepted]
PHST- 2020/04/04 06:00 [pubmed]
PHST- 2021/01/29 06:00 [medline]
PHST- 2020/04/04 06:00 [entrez]
AID - PPL-EPUB-105634 [pii]
AID - 10.2174/0929866527666200403110036 [doi]
PST - ppublish
SO  - Protein Pept Lett. 2020;27(10):1038-1045. doi: 10.2174/0929866527666200403110036.