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Title: “Peri-Natal Toxicity by Type-1 and Type –2 Pyrethroids”

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Title: “Peri-Natal Toxicity by Type-1 and Type –2 Pyrethroids” Medical Research Archives.Vol. 5 Issue 1.January 2017. Perinatal exposure to type I and type II pyrethroids provoke persistent behavioral effects during rat offspring development Abstract Authors: 1 Antonio Francisco Godinho *, Background: Pesticides have been 1 Fabio Anselmo , extensively used around the word but 1 Daniel França Horta concerns over their influence on environment and health is growing. Synthetic pyrethroids are potent insecticides considered to be Authors Note: 1 neurotoxicant. São Paulo State University (UNESP), Hypothesis: We hypothesize that perinatal Institute of Biosciences, Center for exposure to type I (Cypermethrin ) and type II Toxicological Assistance, Laboratory of (d-Allehtrin) pyrethroids would produce Neurobehavioral Research, Botucatu, Sao behavioral effects on offspring during Paulo, Brazil. development. Methods: Pregnant Wistar rats were exposed *Corresponding author during gestation and lactation periods, and their pups were evaluated for somatic and Address: Rua Dr. Antonio Wagner Celso sensory motor changes after weaning, and for Zanin, s/n, CEP 18618-689, Distrito de locomotor activity, motor coordination, and Rubião Junior, Botucatu, SP. Tel.: +55 14 anxiety-like behavior at post natal day 23 and 3813045; Fax: +55 14 3815 3744. 75 (PND23 and PND25). E-mail address: [email protected] (A.F. Results: Cyp and All provoked somatic and Godinho). sensory-motor reflex alterations in weaned pups. In PND23 pups both Cyp and All decreased locomotor activity and motor coordination, and provoke anxiogenic-like effect. In PND75 pups both Cyp and All decreased locomotor activity and motor coordination. Cyp but not All provoked anxiogenic-like effect. Conclusion: Perinatal exposure to selected type I (d-allethrin) and type II (cypermethrin) pyrethroids provoked physical and sensory- motor alterations in weaned pups and persistent behavioral effects during offspring development, suggesting Cyp with a major power to cause neurotoxicity through time. Key words: pyrethroids, development, behavior, neurotoxicity, rat Copyright 2017 KEI Journals. All Rights Reserved. Page | 1 Medical Research Archives.Vol. 5 Issue 1.January 2017. Perinatal exposure to type I and type II pyrethroids provoke persistent behavioral effects during rat offspring development Introduction Because studies evaluating possible Throughout the time pesticides have neurological and neurobehavioral effects of largely benefited the human life through pesticides in children are indeed rare, authors enhancement of agricultural products and identified the need to examine neuro- controlling infectious diseases, but their behavioral and neurodevelopmental status of extensive use, in turn, has caused continuous children exposed to these toxicants[11, 12]. problems of toxicity in nontarget organisms Synthetic pyrethroids are a very potent including humans, due to continued low level insecticides class that is widely used in exposure[1]. forestry, public health, household products In addition, occupational exposition and in agriculture throughout the world and occurs at higher levels compared to the generally considered to be the safest class of population in general, is more significant, and insecticides available[13]. toxicity is enhanced in this special situation[2]. Pyrethroid neurotoxicity to adult Along with the wide use of pesticides animals has been well characterized and in the world, the concerns over their health literature data offers several comprehensive impacts are rapidly growing. There is a huge reviews of pyrethroid toxicity, metabolism, body of evidence on the relation between and actions[14]. However, information exposure to pesticides and elevated rate of regarding the potential developmental neuro- chronic diseases such as different types of toxicity of this class of pesticides is still cancers, diabetes, neurodegenerative disorders scarce. like Parkinson, Alzheimer, and amyotrophic Historically, pyrethroids were grouped lateral sclerosis, birth defects, and into two subclasses (Types I and II) based on reproductive disorders[3,4]. chemical structure and the production of Scientific reports in the last years have either the T (tremor) or CS (choreoathetosis shown that there is a high potential for with salivation) intoxication syndrome pesticides toxicity to humans and the following intravenous or intracerebral association of the indiscriminate use of these administration to rodents[15]. substances with neurodevelopmental disorders Pesticides of pyrethroids group are in children has drawn attention to the various know by provoke nervous paralysis for problems arising from its use and exposures drawing out the opening sodium channels of occurring during the pre and perinatal the neuronal membrane delaying the periods[5,6]. repolarization and by increase nervous For many years now, there has been excitability due to inhibition of the chlorine public concern raised about the potential flow regulated by γ-aminobutyric acid health effects of pesticides on the developing (GABA). Pyrethroids also may act in voltage- fetus and in childhood. Depending on stage of sensitive calcium channels. All effects development, the fetus is selectively sensitive together may contribute to the neurotoxicity to particular chemical toxicants[7,8]. Currently, of these chemical compounds[15.16]. there is much epidemiological evidence Very few studies have reported linking pre- and post-natal exposures to specific functional consequences linked with pesticides with congenital disorders[9]. perinatal exposure to two prototypical With further regard to maternal pyrethroids studied, d-allethrin (type I) and/or exposure to pesticides in early pregnancy, cypermethrin (type II), neither investigated epidemiological studies suggest that maternal persistent behavioral toxicity occurrence employment in agriculture or gardening may thought weaned to adult animals. be a risk factor for birth defects[10]. Copyright 2017 KEI Journals. All Rights Reserved. Page | 2 Medical Research Archives.Vol. 5 Issue 1.January 2017. Perinatal exposure to type I and type II pyrethroids provoke persistent behavioral effects during rat offspring development The present study aimed to study respectively 43 mg/kg for All and 12,5 mg/kg perinatal exposure by d-allethrin (type I) and for Cyp. cypermethrin (type II) pyrethroids in rats, by At birth, all litters were culled to six evaluate social behavior (anxiety) and motor male pups per mother to avoid interference of (locomotor activity and motor coordination) litter size on nutritional state of the pups and, changes during offspring development. consequently, on their development. Whenever possible only male rats were kept Material and Methods within the litter and females were kept just to Animals and treatments maintain equal litter sizes. Pups were All procedures for animal maintained with their mothers and weaned at experimentation were approved by the PND21. institutional Committee of Ethics for Use of Animals, Biosciences Institute, São Paulo Toxicity Evaluations State University (UNESP), in accordance with Mothers international guidelines for animal use and Maternal toxicity during exposition care. period was evaluated through observations on Wistar female and male rats, acquired weight gain, food and water consumption with 22 day-old from our institutional colony measured on a weekly basis, and also were kept under standard conditions (up to weakness, fine to whole-body tremor, four rats per cage, controlled temperature of decreased motor activity, neuromuscular 222°C and 70% humidity, 12-h light/dark weakness, mood swings or some other cycle starting at 6a.m. with light, continuous behavioral manifestation or impaired viability. exhaustion, receiving water and food ad The level of mother‟s exposition was libitum) until they reached 75 days of age. confirmed through insecticides dosage at 20th Animals were mated by keeping overnight gestational day[18]. Additionally number of two females and one male per cage. On the pups per litter was scored. pregnancy day 0 (determined by the presence of sperm in vaginal smears) the pregnant dams Pups were divided in d-allethrin (All), cypermethrin Pup weights at birth and during (Cyp) and control (Ct) groups (N=15), housed developing period were recorded on a weekly singly and were orally administered, by basis. In order to assess the level of offspring gavage, d-allethrin (Sigma Aldrich), pyrethroid exposure, for each litter, pups cypermethrin (Sigma Aldrich), as a single (N=8) were euthanized by decapitation at daily dose dissolved in corn oil or only corn PND-1, 23 and 75, and blood was collected oil as control vehicle. The treatment lasted for pyrethroids quantification[18]. throughout pregnancy and lactation. Choose of dose was made based in PND1 to PND15: There were evaluated the LD50 to no produce clear mother‟s alterations somatic (weight gain, incisors eruption, eyes (e.g. food and water intake reduction and opening, first appearance of hair, unfolding of weakness, fine to whole-body tremor, ears, and testes descent) and sensory-motor decreased motor activity, neuromuscular reflex (postural, negative geotaxis, palmar weakness, weight loss, impaired viability, or grasp, and acoustic startle reflex) some other behavioral manifestation), which development[19]. In rats, palmar grasp reflex is could affect pups normal development[17]. In present at birth, and disappears during growth accordance to this paradigm the 1/20 LD50 and development, contrary to other animals in dosage
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