Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine

Kamboj, Amit; Kiran, Ravi; Sandhir, Rajat

doi:10.1007/s00221-005-0241-5

Cited by 69 publications

(44 citation statements)

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“…3a and 4a). We have earlier reported an increase in lipid peroxidation in brain after long-term carbofuran exposure (Kamboj et al 2006). This increase in oxidative stress seem to arise from either the depletion of GSH or the generation of free radicals and ROS because of the impaired mitochondrial electron transport chain.…”

Section: Results and Disscusionmentioning

confidence: 98%

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Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

et al. 2008

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Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.

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Section: Results and Disscusionmentioning

confidence: 98%

“…Carbofuran has been reported to disturb pro-oxidant/antioxidant balance in brain leading to oxidative stress (Gupta et al 2007;Kamboj et al 2006;Rai and Sharma 2007). Mitochondria are the major cellular sources of reactive oxygen species (ROS) and key contributors to neurodegenerative disorders (Leuner et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

et al. 2008

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“…NAC crosses the blood-brain barrier (Farr et al, 2003), and cysteine can be used in the brain as a GSH precursor. Animal studies have indeed shown that systemic administration of NAC protects the brain against GSH depletion (Aydin et al, 2002;Ercal et al, 1996;Fu et al, 2006;Kamboj et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Lavoie

Murray

Deppen

et al. 2007

Neuropsychopharmacol

328

222

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In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex-and age-matched healthy controls (p ¼ 0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p ¼ 0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

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“…Despite the cholinergic effects of methiocarb, there is little information on other mechanisms of its action. Recent studies indicate that many pesticide intoxications produce oxidative stress by the generation of free radicals and induce tissue lipid peroxidation (LPO) in mammals (Banks and Soliman, 1997;Yarsan et al, 1999;Seth et al, 2000Seth et al, , 2001Kamboj et al, 2006;Karademir Catalgol et al, 2007;Lukaszewicz-Hussain, 2008). Anticholinesterase activity of carbamate pesticides may lead to oxidative injury by producing free radicals in target tissues (Milatovic et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues

Özden

Alpertunga

2009

Drug and Chemical Toxicology

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Methiocarb is an N-methylcarbamate insecticide used worldwide in agriculture and health programs. The aim of this study was to investigate the possible effects of methiocarb to induce lipid peroxidation (LPO) in tissues of male Wistar rats following single and repeated oral exposures. Animals were divided into six different groups, and methiocarb was administered by orally at doses 25, 10, and 2 mg/kg body weight for 1, 5, and 28 days, respectively. Liver, kidney, brain, and testis tissues were taken from the rats for the biochemical examinations. LPO and reduced glutathione (GSH) levels were determined in the tissues. LPO was significantly increased in liver, kidney, brain, and testis after 1-, 5-, and 28-day treatments of methiocarb. GSH levels were significantly increased in the 1-day period and significantly decreased in the 5- and 28-day periods in all tissues after methiocarb administration. It is concluded that methiocarb may induce LPO and produce disturbances on the GSH levels in liver, kidney, testis, and brain of rats. This suggests that methiocarb-induced toxicity may be associated with oxidative stress to cellular membranes. Further studies are required to better understand the role of oxidative stress on methiocarb-induced toxicity.

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Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine

Cited by 69 publications

References 50 publications

Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

Mitochondrial Oxidative Stress and Dysfunction in Rat Brain Induced by Carbofuran Exposure

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues

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