Oxidative damage in chemical teratogenesis

Wells, Peter G.; Kim, P M; Laposa, Rebecca R.; Nicol, Christopher J.B.; Parman, Toufan; Winn, Louise M.

doi:10.1016/s0027-5107(97)00175-9

Cited by 237 publications

(124 citation statements)

References 36 publications

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“…Although various researchers have recently commented on the predictive power of serum GGT [17][18][19], none considered the possibility that serum GGT was a cumulative biomarker of environmental pollutants.…”

Section: Resultsmentioning

confidence: 99%

“…Our updated viewpoint on serum GGT as a marker of exposure to xenobiotics is a more comprehensive interpretation, which includes our earlier proposal that serum GGT reflects oxidative stress. Exposure of cells to xenobiotics directly increases the production of ROS [19]. ROS are also conjugated with GSH [17], and consumption of GSH by conjugation with xenobiotics is related to the depletion of intracellular GSH [17].…”

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confidence: 99%

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Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

2007

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The results of several epidemiological studies of serum γ-glutamyltransferase (GGT) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, such as persistent organic pollutants (POPs). Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes; the predictability of diabetes from obesity was low with GGT at the low end of the normal range; and GGT showed a positive association with known markers of oxidative stress or inflammation. Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re-synthesis of intracellular glutathione; however, this interpretation is not completely satisfying because, in its role of regenerating intracellular glutathione, GGT activity should be antioxidative.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

2007

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“…The mechanisms of anatomical and behavioral teratogenesis may well differ, because it appears that the highest risk of anatomical defects is from first-trimester AED exposure, whereas the highest risk of behavioral defects appears to be from exposure during the third trimester. One of the leading hypotheses of anatomical teratogenesis involves oxidative macromolecular damage from free radicals formed as reactive intermediates of AED metabolism [33]. However, it is unclear if this mechanism contributes to AED-induced behavioral teratogenesis.…”

Section: Proposed Mechanismsmentioning

confidence: 99%

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Meador

Baker

Cohen

et al. 2007

Epilepsy & Behavior

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The majority of children of mothers with epilepsy are normal, but they are at increased risk for developmental delay. Antiepileptic drugs (AEDs) appear to play a role. Our current knowledge is reviewed, including research design issues and recommendations for future research. In animals, exposure of the immature brain to some AEDs can produce widespread neuronal apoptosis and behavioral deficits. The risks of AEDs in humans are less clear, but recent studies raise concerns, especially for valproate. There is a critical need for well-designed systematic research to improve our understanding of AED effects on the fetal brain. KeywordsAntiepileptic drugs; Anticonvulsant drugs; Pregnancy; Teratogenesis; Development; Cognition; Behavior Animal studies on behavioral effects of in utero AED exposureAnimal studies have demonstrated that in utero antiepileptic drug (AED) exposure can produce behavioral as well as anatomical defects, which can occur at dosages lower than those required to produce somatic malformations [1,2]. Gestational or neonatal exposure to benzodiazepines can affect brain chemistry and behavior causing hyperactivity or learning deficits [3,4]. Despite the common use of carbamazepine in humans, very few neurobehavioral studies in animals have been conducted with this AED. In utero carbamazepine exposure did not produce hyperexcitability in primates [5]. Perinatal phenobarbital exposure in rats reduces brain weight [6]. Mice exposed prenatally to phenobarbital have neuronal deficits, reduced brain weight, and impaired development of reflexes, open-field activity, schedule-controlled behavior, spatial learning, and cate-cholamine brain levels [7][8][9][10][11][12]. Gestational or neonatal exposure to phenytoin reduces brain weight [13,14], alters neuronal membranes in the hippocampus [15], delays neurodevelopment [16], and impairs spatial learning and motor coordination [17][18][19][20][21][22][23][24][25]. Hyperactivity has been observed in rats and primates following prenatal exposure to phenytoin [5,23,25]. Gestational primidone in rats produces learning deficits and reduces open-field activity [26]. In utero valproate exposure can alter neuronal membranes [27], decrease brain weight in mice [28], and result in adverse neurobehavioral effects [29,30].

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“…Os sistemas enzimáticos envolvem as enzimas do ciclo redox da glutationa, particularmente a glutationa peroxidase. Estudos demonstraram também que outras enzimas antioxidantes, como glutationa redutase e glicose-6-fosfato-dehidrogenase, apresentaram propriedades protetoras similares à glutationa peroxidase 27,39 . Outros sistemas enzimáticos de defesa antioxidantes operando em conjunto com as enzimas citadas anteriormente incluem a superóxido dismutase (SOD), dependente de Cu 2+ e Zn 2+ como cofatores, onde ocorre a dismutação do radical superóxido em peróxido de hidrogênio e oxigênio (Eq.…”

Section: Introductionunclassified

Sistema antioxidante envolvendo o ciclo metabólico da glutationa associado a métodos eletroanalíticos na avaliação do estresse oxidativo

Júnior¹,

Höehr²,

Vellasco³

et al. 2001

Quím. Nova

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Recebido em 27/1/00; aceito em 12/5/00 ANTIOXIDANT SYSTEM INVOLVING THE GLUTATHIONE METABOLIC CYCLE ASSOCIATED TO ELECTROANALYTICAL METHODS IN THE OXIDATIVE STRESS EVALUATION. The most relevant advances on the analytical applications of glutathione determination based on glutathione redox cycle and the antioxidant system are given. The main enzymes that participate of the glutathione metabolism are the glutathione peroxidase and glutathione reductase. The glutathione peroxidase has a major role in the removal of hydrogen peroxide and lipid peroxides from the cells. These enzymes, operating in tandem with catalase and superoxide dismutase promote a scavenging of oxyradical products in tissues minimizing damages caused by these species. Reduced glutathione is the major intracellular thiol found in mammals and changes in the glutathione concentration in biological fluids or tissues may provide a useful marker in certain disorders like hemolytic anemia, myocardial oxidative stress and in the investigation of some kinds of cancers. Particular attention is devoted to the main advantages supplied by biosensors in which there is an incorporation of bioactive materials for the glutathione determination. The correlation between stability and sensitivity of some reduced glutathione electrochemical sensors is discussed.Keywords: glutathione; electroanalysis; bioelectrochemistry; oxidative stress. Divulgação Quim. Nova, Vol. 24, No. 1, 112-119, 2001. INTRODUÇÃOA incidência de doenças relacionadas a processos cancerígenos no organismo, envolvendo a formação de espéci-es reativas de oxigênio tais como peróxido de hidrogênio e o radical hidroxila, vem merecendo especial atenção nos últimos anos. Existe uma importante correlação entre os níveis de glutationa em sua forma reduzida e os mecanismos enzimáticos de defesa. Esta observação tem promovido uma série de estudos clínicos sobre a interdependência entre o aumento dos ní-veis de glutationa no plasma sangüíneo e doenças cancerígenas em determinados órgãos vitais como rins e pulmões 1,2 . Glutationa, um tripeptídeo (γ-L-glutamil-L-cisteinil-glicina), existe no organismo em suas formas reduzida (GSH) e oxidada (GSSG), atuando direta ou indiretamente em muitos processos biológicos importantes, incluindo a síntese de proteínas, metabolismo e proteção celular 3 . Em particular, problemas na sín-tese e metabolismo da glutationa estão associados a algumas doenças, nas quais os níveis de glutationa e das enzimas que atuam no seu metabolismo podem ser bastante significativos no diagnóstico de alguns tipos de câncer, bem como em outras doenças relacionadas ao estresse oxidativo 4-6 . Mudanças na concentração deste tripeptídeo podem ser um indicador útil em certas desordens fisiológicas como anemias causadas por infecção ou seguidas pela administração de algumas drogas oxidantes 7 , no monitoramento da eficácia de alguns tratamentos usando N-acetil-L-cisteína (NAC) durante o metabolismo do paracetamol 8 , no tratamento de pacientes com artrite reumatróide 9 e na investigação do estresse ...

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Oxidative damage in chemical teratogenesis

Cited by 237 publications

References 36 publications

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

Sistema antioxidante envolvendo o ciclo metabólico da glutationa associado a métodos eletroanalíticos na avaliação do estresse oxidativo

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