Vitamin E attenuates neurotoxicity induced by deltamethrin in rats

Galal et al. BMC Complementary and Alternative Medicine 2014, 14:458 http://www.biomedcentral.com/1472-6882/14/458 RESEARCH ARTICLE Open Access Vitamin E attenuates neurotoxicity induced by deltamethrin in rats Mona K Galal2*, Abdel Azim A Khalaf1, Hanan A Ogaly2 and Marwa A Ibrahim2 Abstract Background: The safety of Deltamethrin (DM) has been raised as a point of concern. The current investigation was envisaged to explore the responsiveness of oxidative stress parameters, DNA fragmentation and expression levels of TP53, cycloxygenase 2 (COX2) and cytochrome p4502E1 (CYP2E1) as toxicological endpoint in rats treated with DM. as well as attention was provided to the neuroprotective effect of vitamin E (VE). Methods: Four different groups of rats were used in this study, group I served as control, group II received DM (0.6 mg/kg BW), group III received both DM plus VE and finally group IV received VE only (200 mg/kg BW). The treatment regimen was extending for one month for all groups and the brain tissues were collected for further analysis. Results: The obtained results showed a highly statistically significant increase in lipid peroxidation (LPO) content, nitric oxide concentration, and DNA fragmentation percentage and expression level of CYP2E1, TP53 and COX2 genes, in addition statistical significant reduction in total antioxidant capacity in DM treated group as compared to control were detected. Oral administration of VE attenuated the neurotoxic effects of DM through improvement of oxidative status, DNA fragmentation percentage and suppressing the expression level of CYP2E1, TP53 and COX2 genes. Conclusion: From this study we concluded that VE supplementation has beneficial impacts on DM neurotoxicity in rats through its antioxidant and antiapoptotic properties. Keywords: Deltamethrin, Brain, Apoptosis, Oxidative stress, Vitamin E Background Although pesticides become instrumental in achieving a significant elevation in crop productivity, they cause serious ecological hazards to the non-target organism [1]. According to WHO [2] roughly three million cases of pesticide poisonings occur annually and an excess of 250,000 deaths worldwide had been reported. The human exposures to pyrethroids were increased since they had been replaced the organophosphorus insecticides [3]. Owing to its low toxicity and its high potency in eradication, DM had become an insecticide of choice in most countries [4]. Although initially thought to be the safest available insecticide, a number of recent reports have been published on its toxicity effect on human, domestics and experimental animals [5,6]. The direct exposure to DM vapours or consumption of * Correspondence: 2 Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt Full list of author information is available at the end of the article polluted food and water are the most common routes of intoxication [7]. DM induced several pathological changes including inhibition of mitotic index, chromosomal aberrations [8], and induction of histological alterations in several important organs [9]. Recently, attention has been focused on the potential relationship between DM exposure and neurodegenerative diseases [10,11]. DM creates serious problem because its accumulation in fatty tissue like brain [12]. Whereas the exact mechanism of DM induced neurotoxicity is still poorly understood. Accumulation of DM in body systems increases the reactive oxygen species (ROS) production leading to oxidative stress and apoptotic cell death [5]. The deleterious effects of free radicals accumulation included damage to all macromolecules including proteins, lipids, and nucleic acids. This is believed to be involved in the etiology of many neurodegenerative diseases [12,13]. Under normal circumstances, the body is endowed with effective antioxidant systems to © 2014 Galal et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Galal et al. BMC Complementary and Alternative Medicine 2014, 14:458 http://www.biomedcentral.com/1472-6882/14/458 Page 2 of 7 combat the menace of oxidative stress. Though, in extreme oxidative challenge, such as those observed in pesticide poisoning [14], the body’s antioxidants machineries are overwhelmed. Vitamin E is considered as the most important lipid-soluble antioxidant that protects the brain from oxidative hazard. Many authors reported the neuroprotective influence of VE [15,16]. VE acts upon cell membranes and has the ability to neutralize compounds which may potentially disrupt membrane stability [17]. Administration of VE decreasing the rate of LPO [11], decreases the autophagy and neuronal death [18], prevents the cytochrome oxidase dysfunction, decreases high energy phosphate compounds and NO in different brain regions as well as it increases the expression level of antiapoptotic gene Bcl-2 [19] leading to decreased severity of neuronal damage. Although previous studies have already presented the toxicity induced by DM, data on neurodegenerative toxicity are scarce. Moreover, there are very limited studies evaluating the neuroprotective effect of VE against DM toxicity. Therefore; the current study was carried out to investigate the protective influence of VE against DM neurotoxicity through monitoring its effect on oxidative status, DNA fragmentation percentage and the expression level of CYP2E1, TP53and COX2 genes in brain tissue. previous studies in which 1/10 LD50 induced biochemical alteration in rat without morbidity [20]. Animals were treated with VE in dose that was proved to have neuroprotective effect [21]. Methods Animals Forty male albino rats, weighing 150–170 g were maintained under standard conditions with free access to food and water. The animals were reared according to the principles of the “Guide for the care and Use of Laboratory Animals” prepared by Beni-Suef University. The Animal care and Use committee of Beni-Suef University approved the study. All efforts were made to minimize animal suffering. Chemicals Deltamethrin (>99% pure) was obtained from KZ pesticide company (Egypt). Vitamin E (α tocopherol) and the rest of chemicals were purchased from Sigma Aldrich chemicals, USA. Experimental protocol After two weeks of acclimation, rats were randomly divided into four equal groups. The group (I) administered corn oil (1 ml/kg BW) and act as control group. The group (II) received oral dose of DM (0.6 mg/kg BW). The group (III) was orally received DM (0.6 mg/kg BW) in combination w (...truncated)