Tags

Type your tag names separated by a space and hit enter

Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse.
Free Radic Biol Med. 2012 Apr 15; 52(8):1294-306.FR

Abstract

A strong association between polymorphisms of the cytochrome P450 (CYP/Cyp) 2D6 gene and risk to Parkinson's disease (PD) is well established. The present study investigated the neuroprotective potential of Cyp2d22, a mouse ortholog of human CYP2D6, in maneb- and paraquat-induced parkinsonism and the mechanisms involved therein along with the effects of resveratrol on various parameters associated with Cyp2d22-mediated neuroprotection. The animals were treated intraperitoneally with resveratrol (10mg/kg, daily) and paraquat (10mg/kg) alone or in combination with maneb (30 mg/kg), twice a week, for 9 weeks, along with their respective controls. The subsets of animals were also treated intraperitoneally with a Cyp2d22 inhibitor, ketoconazole (100mg/kg, daily). Maneb and paraquat reduced Cyp2d22 and vesicular monoamine transporter type 2 (VMAT-2) expressions, the number of tyrosine hydroxylase-positive cells, and dopamine content and increased paraquat accumulation in the nigrostriatal tissues, oxidative stress, microglial activation, neuroinflammation, and apoptosis. Cyp2d22 inhibitor significantly exacerbated all these neurodegenerative indexes. Resveratrol cotreatment, partially but significantly, ameliorated the neurodegenerative changes by altering Cyp2d22 expression and paraquat accumulation. The results obtained in the study demonstrate that Cyp2d22 offers neuroprotection in maneb- and paraquat-induced dopaminergic neurodegeneration and resveratrol enhances its neuroprotective credentials by influencing Cyp2d22 expression and paraquat accumulation.

Authors+Show Affiliations

CSIR-Indian Institute of Toxicology Research, M. G. Marg, Post Box 80, Lucknow 226 001, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22334051

Citation

Srivastava, Garima, et al. "Resveratrol Potentiates Cytochrome P450 2 D22-mediated Neuroprotection in Maneb- and Paraquat-induced Parkinsonism in the Mouse." Free Radical Biology & Medicine, vol. 52, no. 8, 2012, pp. 1294-306.
Srivastava G, Dixit A, Yadav S, et al. Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. Free Radic Biol Med. 2012;52(8):1294-306.
Srivastava, G., Dixit, A., Yadav, S., Patel, D. K., Prakash, O., & Singh, M. P. (2012). Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. Free Radical Biology & Medicine, 52(8), 1294-306. https://doi.org/10.1016/j.freeradbiomed.2012.02.005
Srivastava G, et al. Resveratrol Potentiates Cytochrome P450 2 D22-mediated Neuroprotection in Maneb- and Paraquat-induced Parkinsonism in the Mouse. Free Radic Biol Med. 2012 Apr 15;52(8):1294-306. PubMed PMID: 22334051.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse. AU - Srivastava,Garima, AU - Dixit,Anubhuti, AU - Yadav,Sharawan, AU - Patel,Devendra Kumar, AU - Prakash,Om, AU - Singh,Mahendra Pratap, Y1 - 2012/02/11/ PY - 2011/11/22/received PY - 2012/01/10/revised PY - 2012/02/03/accepted PY - 2012/2/16/entrez PY - 2012/2/16/pubmed PY - 2012/8/17/medline SP - 1294 EP - 306 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 52 IS - 8 N2 - A strong association between polymorphisms of the cytochrome P450 (CYP/Cyp) 2D6 gene and risk to Parkinson's disease (PD) is well established. The present study investigated the neuroprotective potential of Cyp2d22, a mouse ortholog of human CYP2D6, in maneb- and paraquat-induced parkinsonism and the mechanisms involved therein along with the effects of resveratrol on various parameters associated with Cyp2d22-mediated neuroprotection. The animals were treated intraperitoneally with resveratrol (10mg/kg, daily) and paraquat (10mg/kg) alone or in combination with maneb (30 mg/kg), twice a week, for 9 weeks, along with their respective controls. The subsets of animals were also treated intraperitoneally with a Cyp2d22 inhibitor, ketoconazole (100mg/kg, daily). Maneb and paraquat reduced Cyp2d22 and vesicular monoamine transporter type 2 (VMAT-2) expressions, the number of tyrosine hydroxylase-positive cells, and dopamine content and increased paraquat accumulation in the nigrostriatal tissues, oxidative stress, microglial activation, neuroinflammation, and apoptosis. Cyp2d22 inhibitor significantly exacerbated all these neurodegenerative indexes. Resveratrol cotreatment, partially but significantly, ameliorated the neurodegenerative changes by altering Cyp2d22 expression and paraquat accumulation. The results obtained in the study demonstrate that Cyp2d22 offers neuroprotection in maneb- and paraquat-induced dopaminergic neurodegeneration and resveratrol enhances its neuroprotective credentials by influencing Cyp2d22 expression and paraquat accumulation. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/22334051/Resveratrol_potentiates_cytochrome_P450_2_d22_mediated_neuroprotection_in_maneb__and_paraquat_induced_parkinsonism_in_the_mouse_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(12)00082-2 DB - PRIME DP - Unbound Medicine ER -