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Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson's disease phenotype in mouse: mechanism of neurodegeneration.
Brain Res. 2006 Apr 07; 1081(1):9-18.BR

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder contributed by the combination of age, genetic and environmental factors. Several studies have clearly shown increase in the incidences of PD in the rural environments and hypothesized the involvement of pesticides such as paraquat and maneb in neurodegeneration. These studies have prompted researchers to develop paraquat and maneb models to study the effect of co-treatment of maneb and paraquat on neuronal toxicity; however, the mechanism underlying maneb and paraquat co-treatment induced neuronal toxicity has not yet been clearly understood. The involvement of cytochrome P4502E1 and glutathione S-transferases A4-4 enzymes in the detoxification of several pesticides such as atrazine, fenamirol, organophosphorous insecticide parathion, methoxychlor, diethyl dithiocarbamate and paraquat has been known. The contribution of CYP2E1 and GSTA4-4 in neuronal toxicity has also been reported. The present study was therefore undertaken to investigate the mechanism of maneb- and paraquat-induced neurodegeneration by estimating the level of antioxidant defense enzymes in the striatum and measuring the differential expressions of CYP2E1 and GSTA4-4 genes. Animals were treated with and without maneb (30 mg/kg, i.p.) or paraquat (10 mg/kg, i.p.) either alone or in combination in exposure time-dependent manner. A significant increase in catalase, glutathione S-transferase and lipid peroxidation in the striatum was found following 3, 6 and 9 weeks of co-treatment as compared with individual treatment or controls. Individual treatment of maneb or paraquat did not exhibit any significant alteration in CYP2E1 and GSTA4-4 expression up to 6 weeks; however, an augmentation in CYP2E1 and GSTA4-4 expression was observed in the animals exposed to maneb or paraquat for 9 weeks. Augmentation in the expression of CYP2E1 and GSTA4-4 was more pronounced in the animals treated with maneb and paraquat in combination for nine weeks. A significant reduction in the augmented lipid peroxidation in the striatum was observed when the striatum was pre-administered with CYP2E1 inhibitors; however, glutathione pre-administration induced lipid peroxidation. Results obtained from the present investigation suggest the involvement of CYP2E1 and GSTA4-4 in the augmentation of the lipid peroxidation thereby enhancing neurodegeneration.

Authors+Show Affiliations

Industrial Toxicology Research Centre (ITRC), Mahatma Gandhi Marg, Post Box- 80, Lucknow- 226 001, UP, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16510128

Citation

Patel, Suman, et al. "Status of Antioxidant Defense System and Expression of Toxicant Responsive Genes in Striatum of Maneb- and Paraquat-induced Parkinson's Disease Phenotype in Mouse: Mechanism of Neurodegeneration." Brain Research, vol. 1081, no. 1, 2006, pp. 9-18.
Patel S, Singh V, Kumar A, et al. Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson's disease phenotype in mouse: mechanism of neurodegeneration. Brain Res. 2006;1081(1):9-18.
Patel, S., Singh, V., Kumar, A., Gupta, Y. K., & Singh, M. P. (2006). Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson's disease phenotype in mouse: mechanism of neurodegeneration. Brain Research, 1081(1), 9-18.
Patel S, et al. Status of Antioxidant Defense System and Expression of Toxicant Responsive Genes in Striatum of Maneb- and Paraquat-induced Parkinson's Disease Phenotype in Mouse: Mechanism of Neurodegeneration. Brain Res. 2006 Apr 7;1081(1):9-18. PubMed PMID: 16510128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Status of antioxidant defense system and expression of toxicant responsive genes in striatum of maneb- and paraquat-induced Parkinson's disease phenotype in mouse: mechanism of neurodegeneration. AU - Patel,Suman, AU - Singh,Virendra, AU - Kumar,Abhai, AU - Gupta,Yogendra Kumar, AU - Singh,Mahendra Pratap, Y1 - 2006/02/28/ PY - 2005/12/01/received PY - 2006/01/16/revised PY - 2006/01/17/accepted PY - 2006/3/3/pubmed PY - 2006/7/11/medline PY - 2006/3/3/entrez SP - 9 EP - 18 JF - Brain research JO - Brain Res VL - 1081 IS - 1 N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder contributed by the combination of age, genetic and environmental factors. Several studies have clearly shown increase in the incidences of PD in the rural environments and hypothesized the involvement of pesticides such as paraquat and maneb in neurodegeneration. These studies have prompted researchers to develop paraquat and maneb models to study the effect of co-treatment of maneb and paraquat on neuronal toxicity; however, the mechanism underlying maneb and paraquat co-treatment induced neuronal toxicity has not yet been clearly understood. The involvement of cytochrome P4502E1 and glutathione S-transferases A4-4 enzymes in the detoxification of several pesticides such as atrazine, fenamirol, organophosphorous insecticide parathion, methoxychlor, diethyl dithiocarbamate and paraquat has been known. The contribution of CYP2E1 and GSTA4-4 in neuronal toxicity has also been reported. The present study was therefore undertaken to investigate the mechanism of maneb- and paraquat-induced neurodegeneration by estimating the level of antioxidant defense enzymes in the striatum and measuring the differential expressions of CYP2E1 and GSTA4-4 genes. Animals were treated with and without maneb (30 mg/kg, i.p.) or paraquat (10 mg/kg, i.p.) either alone or in combination in exposure time-dependent manner. A significant increase in catalase, glutathione S-transferase and lipid peroxidation in the striatum was found following 3, 6 and 9 weeks of co-treatment as compared with individual treatment or controls. Individual treatment of maneb or paraquat did not exhibit any significant alteration in CYP2E1 and GSTA4-4 expression up to 6 weeks; however, an augmentation in CYP2E1 and GSTA4-4 expression was observed in the animals exposed to maneb or paraquat for 9 weeks. Augmentation in the expression of CYP2E1 and GSTA4-4 was more pronounced in the animals treated with maneb and paraquat in combination for nine weeks. A significant reduction in the augmented lipid peroxidation in the striatum was observed when the striatum was pre-administered with CYP2E1 inhibitors; however, glutathione pre-administration induced lipid peroxidation. Results obtained from the present investigation suggest the involvement of CYP2E1 and GSTA4-4 in the augmentation of the lipid peroxidation thereby enhancing neurodegeneration. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16510128/Status_of_antioxidant_defense_system_and_expression_of_toxicant_responsive_genes_in_striatum_of_maneb__and_paraquat_induced_Parkinson's_disease_phenotype_in_mouse:_mechanism_of_neurodegeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)00175-2 DB - PRIME DP - Unbound Medicine ER -