Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Stephanou, Panayiotis; Konstandi, Maria; Pappas, Periklis; Marselos, Marios

doi:10.1007/bf03189998

Cited by 49 publications

(46 citation statements)

References 25 publications

(20 reference statements)

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“…Inhibition of Na + /K + ATPase, an important enzyme in muscle contraction and nerve excitability, in addition to decreased motor conduction velocities may explain the suppression of motor activity observed in B(a)P intoxicated rats (Kim et al, 2000;Saunders et al, 2001). Inhibition of tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, can lead to reductions in striatal dopamine (Stephanou et al, 1998;Andersson et al, 1998), which may also contribute to the suppression in motor activity documented in this study. Furthermore, there is also strong experimental evidence showing that oxidative stress and lipid peroxidative products can cause decreases in dopamine and inhibit Na+/K+ ATPase activity as well (Madrigal et al, 2003).…”

Section: Discussionmentioning

confidence: 85%

“…Alterations in central monoamines have been reported after single administration of B(a)P (Stephanou et al, 1998;Jayasekara et al, 1992). Also, potent acetylcholinesterase inhibition has been reported in vitro when B(a)P was administered with or without chlopyrifos (Jett et al, 1999).…”

Section: Introductionmentioning

confidence: 96%

“…Although the liver is primarily involved in the metabolism of B(a)P, metabolism also occurs, albeit to a lesser extent, in extrahepatic tissues (WHO, 1999). Experimental data demonstrate that similar to most lipophilic compounds, BaP easily crosses the blood-brain barrier; and thereby gains direct access to the central nervous system (Das et al, 1985;WHO, 1999;Ramesh et al, 2001;Stephanou et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

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Benzo(a)pyrene‐induced acute neurotoxicity in the F‐344 rat: role of oxidative stress

Saunders

Das

Ramesh

et al. 2006

J of Applied Toxicology

149

125

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Given the link between neurotoxicity and exposure to pollutants, the potential behavioral neurotoxicity of benzo(a)pyrene [B(a)P] was investigated. Studies have established that B(a)P requires metabolic activation to highly reactive species to elicit many of its adverse effects. This study investigated the perturbation of nervous system function by correlating behavioral changes with the metabolism of B(a)P, antioxidant enzyme levels and lipid peroxidation in selected brain regions. The neurobehavioral effects of single oral doses of B(a)P (25-200 mg kg(-1) body weight) on motor activity were examined in male F-344 rats at 2, 4, 6, 12, 24, 48, 72 and 96 h post treatment. Parent B(a)P and metabolites were measured at the above mentioned time points by reverse phase HPLC. The activity of several antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and levels of malondialdehyde were determined at 6 and 96 h in both the striatum and hippocampus of B(a)P exposed rats. Suppression of motor activity (up to 70%) reached a maximum at 6 h, but was reversible at 96 h in all dose groups. The kinetics of disposition data show a strong link between B(a)P metabolism and the onset and duration of behavioral effects. Benzo(a)pyrene caused a 15-70% inhibition in the activity of superoxide dismutase and glutathione peroxidase and an enhancement in catalase and lipid peroxidation (up to 68%) in the striatum and hippocampus at 6 and 96 h post treatment, respectively. These findings suggest that B(a)P-induced acute neurobehavioral toxicity may occur through oxidative stress due to inhibition of the brain antioxidant scavenging system.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

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Benzo(a)pyrene‐induced acute neurotoxicity in the F‐344 rat: role of oxidative stress

Saunders

Das

Ramesh

et al. 2006

J of Applied Toxicology

149

125

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“…Verification of drug-induced modulation of noradrenaline (NA) was achieved by measuring NA in hypothalamus using ion-pairing reverse phase high-performance liquid chromatography (HPLC) with electrochemical detection [37,38].…”

Section: Methodsmentioning

confidence: 99%

Predominant Role of Peripheral Catecholamines in the Stress‐Induced Modulation of CYP1A2 Inducibility by Benzo(α)pyrene

Konstandi¹,

Lang

Kostakis³

et al. 2007

Basic Clin Pharma Tox

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Abstract:The potential involvement of catecholamines and in particular of α 2 -adrenoceptor-related signalling pathways, in the regulation of drug-metabolizing enzymes by stress was investigated in Wistar rats after exposure to the environmental pollutant benzo( α )pyrene. For this purpose, total cytochrome P450 content, the CYP1A2 mRNA levels, 7-methoxyresorufin-O-dealkylase (MROD), 7-pentoxyresorufin-O-dealkylase (PROD) and p-nitrophenol hydroxylase activity levels were determined in the livers of rats exposed to repeated restraint stress after treatment with benzo( α )pyrene coupled with pharmacological manipulations of peripheral and/or central catecholamines and α 2 -adrenoceptors. The data show that stress is a significant factor in the regulation of CYP1A2 induction and that catecholamines play a central role in the stress-mediated modulation of hepatic CYP1A2 inducibility by benzo( α )pyrene. The up-regulating effect of stress on benzo( α )pyrene-induced CYP1A2 gene expression was eliminated after a generalized catecholamine depletion with reserpine. Similarly, in a state where only peripheral catecholamines were depleted and central catecholamines remained intact after guanethidine administration, the up-regulating effect of stress was eliminated. It is apparent that stress up-regulates the induction of CYP1A2 by benzo( α )pyrene mainly via peripheral catecholamines, while central catecholamines hold a minor role in the regulation. Pharmacological manipulations of α 2 -adrenoceptors appear to interfere with the effect of stress on the regulation of CYP1A2 inducibility. Either blockade or stimulation of α 2 -adrenoceptors with atipamezole and dexmedetomidine respectively, eliminated the up-regulating effect of stress on CYP1A2 benzo( α )pyrene-induced expression, while it enhanced MROD activity. In contrast, stress and pharmacological manipulations of catecholamines and α 2 -adrenoceptors did not affect total P450 content, the CYP2B1/2-dependent PROD and the CYP2E1-dependent p-nitrophenol hydroxylase activities. In conclusion, stress is a significant factor in the regulation of the CYP1A2 inducibility by benzo( α )pyrene, which in turn is involved in the metabolism of a large spectrum of toxicants, drugs and carcinogenic agents. Although the mechanism underlying the stress effect on CYP1A2 induction has not been clearly elucidated, it appears that peripheral catecholamines hold a predominant role, while central catecholamines and in particular, central noradrenergic pathways hold a minor role.

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“…B(a)P-induced acute neurobehavioral toxicity through oxidative stress has been observed (Saunders et al, 2006). Alterations in the dopaminergic and serotoninergic systems throughout the brain have been reported after single administration of B(a)P (Jayasekara et al, 1992;Stephanou et al, 1998). Acetylcholinesterase (AChE) inhibition has also been found in vitro when B(a)P was administered (Jett et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Adverse effect of sub-chronic exposure to benzo(a)pyrene and protective effect of butylated hydroxyanisole on learning and memory ability in male Sprague-Dawley rat

et al. 2014

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-Previous studies demonstrate that benzo(a)pyrene (B(a)P) can affect hippocampal function and cause spatial cognition impairment. However, the mechanism is incomplete. Some evidence implies that B(a)P may cause an oxidative damage linking to the function of the hippocampus and antioxidant can prevent the oxidative damage in rats, but the ATPase and Ca 2+ in the hippocampus and the protective effect of butylated hydroxyanisole (BHA) have not been studied. This study aimed to investigate the damage of toxicity further induced by B(a)P in hippocampus and the protective effect of BHA. Ninety-six male Sprague-Dawley (SD) rats were randomly divided into four groups (solvent control group, BHA-group, B(a)P-exposed group and B(a)P-BHA-combination group), with daily administration for 90 days. Morris water maze (MWM) was employed to evaluate the learning and memory ability. The levels of malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase activity in hippocampus were measured by commercial kits. The concentration of Ca 2+ in rat hippocampus was detected by fluorescent labeling. In behavior test it showed that there was an adverse effect on rats in the B(a)P -group. The levels of MDA content and Ca 2+ content were significantly increased in the B(a)P group, while the activities of SOD and ATPase were significantly decreased. In the B(a)P-BHA group, the change of each index diminished significantly. The results suggested that the neurobehavioral toxicity of B(a)P might have a close relationship with oxidative damage, resulted in decreasing of ATPase activities and increasing of Ca 2+ concentration in the hippocampus. Furthermore, BHA can prevent these damages.

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Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Cited by 49 publications

References 25 publications

Benzo(a)pyrene‐induced acute neurotoxicity in the F‐344 rat: role of oxidative stress

Benzo(a)pyrene‐induced acute neurotoxicity in the F‐344 rat: role of oxidative stress

Predominant Role of Peripheral Catecholamines in the Stress‐Induced Modulation of CYP1A2 Inducibility by Benzo(α)pyrene

Adverse effect of sub-chronic exposure to benzo(a)pyrene and protective effect of butylated hydroxyanisole on learning and memory ability in male Sprague-Dawley rat

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