DNA Damage after Acute and Chronic Treatment with Malathion in Rats

Réus, Gislaine Z.; Valvassori, Samira S.; Nuernberg, Hellen; Comim, Clarissa M.; Stringari, Roberto B.; Padilha, Peterson Teodoro; Leffa, Daniela Dimer; Tavares, Priscila; Dagostim, Gracilene P; Paula, M.M.S.; Andrade, Vanessa Moraes de; Quevedo, Joao L De

doi:10.1021/jf800910q

Cited by 36 publications

(24 citation statements)

References 49 publications

(72 reference statements)

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“…The interference of acute malathion treatment by increasing end products of protein and lipid peroxidation [11,[13][14][15]21], as well as decreasing antioxidant-related enzymes [11,12,15,21], has been pointed out in previous studies. Similar to zinc, repeated low doses of malathion seem to induce an adaptive response in AChE activity in the rat brain [49].…”

Section: Controlmentioning

confidence: 95%

“…Organophosphate has been considered as an important risk factor for depression and correlated to suicide attempts [9] and has been used as a model of depressive-like behaviour in animals [10]. Malathion, a pesticide widely used to fight fleas, lice, mosquitoes and flies, is thought to be one of the main agents leading to human organophosphate intoxication in the Santa Catarina state, Southern Brazil [11].Along with the induction of depressive-like behaviour in animal models of depression [10,12], malathion toxicity causes impairment in the antioxidant defense [11,12], and produces an increase in several markers of oxidative stress in the rat brain, such as lipid peroxidation, protein carbonylation and DNA damage [13][14][15], but gender differences have not yet been studied.The effects of metals have been under investigation for decades and attention is naturally focused on the most toxic metals such as cadmium, nickel, lead, mercury and arsenic [1]. On the other side, zinc has been considered a relatively safe metal [16] owing to its auto-regulatory metabolism [17] and little attention has been paid to its acute toxicity.…”

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confidence: 99%

“…Along with the induction of depressive-like behaviour in animal models of depression [10,12], malathion toxicity causes impairment in the antioxidant defense [11,12], and produces an increase in several markers of oxidative stress in the rat brain, such as lipid peroxidation, protein carbonylation and DNA damage [13][14][15], but gender differences have not yet been studied.…”

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Gender Effects of Acute Malathion or Zinc Exposure on the Antioxidant Response of Rat Hippocampus and Cerebral Cortex

Maris

Franco

Mitozo³

et al. 2010

Basic Clin Pharma Tox

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Gender is one of the most important factors in mammalian development and response to exogenous agents. Although there is increasing evidence that health effects of toxic xenobiotics differ in prevalence or are manifested differently in male and female, the molecular mechanisms related to these events remain unclear. In order to investigate the possible influence of gender, male and female Wistar rats from the same litter were exposed to zinc chloride (5 mg ⁄ kg, i.p.) or malathion (250 mg ⁄ kg, i.p.) 24 hr prior to the analyses of biochemical parameters related to the cholinergic and glutathione-antioxidant systems in cerebral cortex and hippocampus. After treatments, acetylcholinesterase (AChE) activity was reduced in the hippocampus and cerebral cortex of male and female rats treated with malathion, but the effect was more pronounced in the male group. Glutathione reductase (GR) and c-glutamyl-transpeptidase activities were reduced in the hippocampus of males and females and a gender-specific effect of malathion was seen for glutathione S-transferase (GST), which was decreased only in male hippocampus and cortex, and for male cortical GR. Zinc chloride treatment decreased AChE activity in male and female cerebral cortex, with no obvious effect in the hippocampus. Male-specific antioxidant-related enzyme activity reductions were seen after zinc treatment for cortical GR, GST, glutathione peroxidase and glucose-6-phosphate dehydrogenase; and hippocampal GR. These results clearly demonstrate a greater detrimental effect on antioxidant-related enzyme activities in male hippocampus and cerebral cortex when rats were acutely exposed to malathion and zinc, demonstrating that the research on gender-related differences in health effects caused by xenobiotic and ⁄ or essential elements requires further attention.Gender-based differences in the metabolism constitute a major topic in biology, and sex-dependent toxicity permeates the literature for a series of factors. Some examples of research areas where gender differences are important determinants of toxicity are: metal toxicity [1], pharmacokinetics [2], hormone metabolism [3], xenobiotics metabolism [4] and traumatic injury vulnerability [5]. The relevance of studying gender-dependent toxicity has been stressed before: 'Gender may be the most important factor in mammalian development and response to exogenous agents' [6].Incidental or intentional organophosphate intoxication is a relevant health problem in developing countries [7]. Despite the limitation of population analysis, neurobehavioural impairment might be the consequence of an acute poisoning, and possibly the consequence of relatively high and prolonged exposure [8]. Organophosphate has been considered as an important risk factor for depression and correlated to suicide attempts [9] and has been used as a model of depressive-like behaviour in animals [10]. Malathion, a pesticide widely used to fight fleas, lice, mosquitoes and flies, is thought to be one of the main agents leading to human organop...

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Section: Controlmentioning

confidence: 95%

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confidence: 99%

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Gender Effects of Acute Malathion or Zinc Exposure on the Antioxidant Response of Rat Hippocampus and Cerebral Cortex

Maris

Franco

Mitozo³

et al. 2010

Basic Clin Pharma Tox

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“…Rats were treated acutely or for 28 days with 0, 25, 50, 100, or 150 mg/kg/day malathion via intraperitoneal injection, and the two highest doses (when given repeatedly) were associated with an increased DNA damage index in peripheral blood and brain (hippocampus). Frequency of micronuclei was increased only at 150 mg/kg/day and only after repeated treatment (432). In another study, acute doses of 2.5, 5, and 10 mg/kg malathion induced chromosome aberrations and sperm abnormalities in sister chromatid exchange and sperm abnormality assays in mice (433).…”

Section: Genetic and Related Cellular Effect Studiesmentioning

confidence: 98%

Organophosphorus Pesticides

Storm¹

2012

Patty's Toxicology

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Most organophosphorus compounds today fall into two general groups: the so‐called nerve agents, that are very acutely toxic and organophosphorus pesticides that are less toxic. Nerve agents were generally the first toxic organophosphorus developed, and were the original basis for organophosphorus pesticides. Interest about nerve agents has increased lately given concerns about their potential use in terrorist acts. Organophosphate nerve agents and pesticides are a highly diverse group of chemicals. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). At present, the widest use of organophosphorus compounds is as pesticides, although they have also been used as therapeutic agents, gasoline additives, hydraulic fluids, cotton defoliants, fire retardants, plastic components, growth regulators, and industrial intermediates to a much smaller extent. Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk (1991) [2], for example, categorized them into four main groups I–IV based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than group I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio, or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates, phosphorothiolates, phosphorodithioates, and phosphorodithiolates) are far more numerous than phosphates and include well‐recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates, and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously and comprehensively reviewed. In addition, information regarding the toxicity of organophosphorus pesticides in particular has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data have been made publicly available by the U.S. EPA on its Internet Web site ( www.epa.gov/pesticides ). The following discussion draws heavily from recent reviews and also includes summaries of relevant toxicity data submitted to, and made available by, the U.S. EPA.

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“…Chinese Hamster Ovary ( CHO) cells (Vigreux & et al, 1998) Cerebral tissue and peripheral blood of rats (Reus, & et al, 2008) P,P'-DDT CCl 3…”

Section: How To Evaluate Dna Damage By Comet Assaymentioning

confidence: 99%