Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 1, January, p. 5–14
doi: 10.17219/acem/67314
Publication type: original article
Language: English
Download citation:
The protective action of tocopherol and acetylsalicylic acid on the behavior of rats treated with dioxins
1 Department of Nervous System Diseases, Wroclaw Medical University, Poland
2 Independent Laboratory of Clinical Neurotoxicology and Environmental Diagnostics, Wroclaw Medical University, Poland
Abstract
Background. Dioxins contribute to neurological disorders in humans and animals, causing also neurological disorders in offspring during prenatal and postnatal periods. These compounds significantly affect the development of the central nervous system (CNS) structures, which results in behavioral changes. Tocopherol (TCP) and acetylsalicylic acid (ASA) may provide protective measures to reduce the inflammatory effects in the CNS associated with free radicals generated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), thus contributing to the reduction of the negative effects of dioxin.
Objectives. The main objective of this study was to determine the influence of dioxin on rats and their behavioral functions, and to ascertain whether a combined administration of TCP and ASA to rats treated with TCDD shows the possibility of potential protective effect on the functioning of the CNS.
Material and Methods. Experiments were performed on 75 female and 12 male Buffalo strain rats, which are offspring of females from particular study groups. TCDD was used in the experiments, TCP and ASA were administered orally every day for 3 weeks. Animals were subjected to behavioral testing: the tail and swimming tests.
Results. During the observation of the offspring of both sexes born to females exposed to TCDD, males did not demonstrate any attempt to swim, whereas in females, the immobility time was significantly extended. Assessing the response times from the tail test in the animals treated with dioxins in relation to the control group, it was demonstrated that the response time was extended in the 3rd measurement in both females and males.
Conclusion. Dioxin is characterized by neurotoxic effect causing behavioral disorders associated with prolonged response times. The use of TCP after the administration of dioxins causes a significant reduction and improvement of reflex response times. In contrast, ASA reduces the reflex response times also in the offspring of females exposed to TCDD and ASA.
Key words
central nervous system, 2,3,7,8-tetrachlorodibenzo-p-dioxin, tocopherol, acetylsalicylic acid, behavioral functions
References (57)
- Crow KD. Chloracne and its potential clinical implications. Clin Exp Dermatol. 1981;6:243–257.
- Arora S. Leptin and its metabolic interactions: An update. Diabetes Obes Metab. 2008;10:973–993.
- Ciftci O, Vardi N, Ozdemir I. Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats. Environ Toxicol. 2013;28(3):146–154.
- Stevens EA, Mezrich JD, Bradfield CA. The aryl hydrocarbon receptor: A perspective on potential roles in the immune system. Immunology. 2009;127:299–311.
- Stockinger B, Hirota K, Duarte J, Veldhoen M. External influences on the immune system via activation of the aryl hydrocarbon receptor. Semin Immunol. 2011;23:99–105.
- Teraoka H, Kubota A, Dong W, et al. Role of the cyclooxygenase 2-thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo. Toxicol Appl Pharmacol. 2009;234:33–40.
- Clements RJ, Lawrence RC, Blank JL. Effects of intrauterine 2,3,7,8-tetrachlorodibenzo-p-dioxin on the development and function of the gonadotrophin releasing hormone neuronal system in the male rat. Reprod Toxicol. 2009;28:38–45.
- Fukushima K, Tsukimori K, Li D, et al. Effect of transient TCDD exposure on immortalized human trophoblast-derived cell lines. Hum Exp Toxicol. 2012;31:550–556.
- Fernández M, Paradisi M, D’Intino G, et al. A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain. J Neurochem. 2010;115:897–909.
- Hood DB, Woods L, Brown L, Johnson S, Ebner FF. Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function. Neurotoxicology. 2006;27:1032–1042.
- Nishijo M, Kuriwaki JI, Hori E, Tawara K, Nakagawa H, Nishijo H. Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats. Toxicol Lett. 2007;173:41–47.
- Williamson MA, Gasiewicz TA, Opanashuk LA. Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: Implications for development and dioxin neurotoxicity. Toxicol Sci. 2005;83:340–348.
- Nishijo M, Tawara K, Nakagawa H, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference. J Expo Sci Environ Epidemiol. 2008;18:246–251.
- Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes. 2008;57:95–101.
- Dong B, Cheng W, Li W, et al. FRET analysis of protein tyrosine kinase c-Src activation mediated via aryl hydrocarbon receptor. Biochim Biophys Acta. 2011;1810:427–431.
- Rosińczuk J, Dymarek R, Całkosiński I. Histopathological, ultrastructural, and immunohistochemical assessment of hippocampus structures of rats exposed to TCDD and high doses of tocopherol and acetylsalicylic acid. Bio Med Res Int. 2015;2015:645603.
- Yoon CY, Park M, Kim BH, et al. Gene expression profile by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the liver of wild-type (AhR+/+) and aryl hydrocarbon receptor-deficient (AhR-/-) mice. J Vet Med Sci. 2006;68:663–668.
- Całkosiński I, Borodulin-Nadzieja L, Stańda M, Wasilewska U, Cegielski M. Influence of a single dose of TCDD on estrogen levels and reproduction in female rats. Vet Med. 2003;59:536–538.
- Całkosiński I, Borodulin-Nadzieja L, Wasilewska U, et al. Effect of dioxins on reproduction in rats in vivo. Adv Clin Exp Med. 2004;13:885–890.
- Całkosiński I, Wasilewska U, Borodulin-Nadzieja L, et al. Influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the functioning and structure of ovaries and testicles in the offspring of rats. Vet Med. 2004;60:1218–1221.
- Całkosiński I, Dobrzyński M, Całkosińska M, et al. Characterization of an inflammatory response. Adv Hyg Exp Med. 2009;63:395–408.
- Wen S, Gong Y, Li J, Shi T, Zhao Y, Wu Y. Particle-bound PCDD/Fs in the atmosphere of an electronic waste dismantling area in China. Biomed Environ Sci. 2011;24:102–111.
- Geusau A, Tschachler E, Meixner M, Päpke O, Stingl G, McLachlan M. Cutaneous elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Br J Dermatol. 2001;145:938–943.
- Geusau A, Abraham K, Geissler K, Sator MO, Stingl G, Tschachler E. Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: Clinical and laboratory effects. Environ Health Perspect. 2001;109:865–869.
- Cheshenko K, Brion F, Le Page Y, et al. Expression of zebra fish aromatase cyp19a and cyp19b genes in response to the ligands of estrogen receptor and aryl hydrocarbon receptor. Toxicol Sci. 2007;96:255–267.
- Mukai M, Lin TM, Peterson RE, Cooke PS, Tischkau SA. Behavioral rhythmicity of mice lacking AhR and attenuation of light-induced phase shift by 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Rhythms. 2008;23:200–210.
- Oehme M, Biseth A, Schlabach M, Wiig Ø. Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans and non-ortho substituted biphenyls in polar bear milk from Svalbard (Norway). Environ Pollut. 1995;90:401–407.
- Oehme M, Schlabach M, Hummert K, Luckas B, Nordøy ES. Determination of levels of polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls and pesticides in harp seals from the Greenland Sea. Sci Total Environ. 1995;162:75–91.
- Carvalho PSM, Tillitt DE. 2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout. Environ Sci Technol. 2004;38:6300–6306.
- Tsukamoto H, Rippe R, Niemelä O, Lin M. Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis. J Gastroenterol Hepatol. 1995;10:50–53.
- Tue NM, Suzuki G, Takahashi S, et al. Evaluation of dioxin-like activities in settled house dust from Vietnamese E-waste recycling sites: Relevance of polychlorinated/brominated dibenzo-p-dioxin/furans and dioxin-like PCBs. Environ Sci Technol. 2010;44:9195–9200.
- Hassoun EA, Vodhanel J, Abushaban A. The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure. J Biochem Mol Toxicol. 2004;18:196–203.
- Hassoun EA, Vodhanel J, Holden B, Abushaban A. The effects of ellagic acid and vitamin E succinate on antioxidant enzymes activities and glutathione levels in different brain regions of rats after subchronic exposure to TCDD. J Toxicol Environ Health A. 2006;69:381–393.
- Kim SY, Lee HG, Choi EJ, Park KY, Yang JH. TCDD alters PKC signaling pathways in developing neuronal cells in culture. Chemosphere. 2007;67:421–427.
- Kim SY, Yang JH. Neurotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in cerebellar granule cells. Exp Mol Med. 2005;37:58–64.
- Li W, Matsumura F. Significance of the nongenomic, inflammatory pathway in mediating the toxic action of TCDD to induce rapid and long-term cellular responses in 3T3-L1 adipocytes. Biochemistry (Mosc). 2008;47:13997–4008.
- MacDonald CJ, Cheng RYS, Roberts DD, Wink DA, Yeh GC. Modulation of carcinogen metabolism by nitric oxide-aspirin 2 is associated with suppression of DNA damage and DNA adduct formation. J Biol Chem. 2009;284:22099–22107.
- MacDonald CJ, Ciolino HP, Yeh GC. The drug salicylamide is an antagonist of the aryl hydrocarbon receptor that inhibits signal transduction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Res. 2004;64:429–434.
- Maharaj H, Maharaj DS, Daya S. Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicity. Metab Brain Dis. 2006;21:189–199.
- Wang SJ. Facilitatory effect of aspirin on glutamate release from rat hippocampal nerve terminals: Involvement of protein kinase C pathway. Neurochem Int. 2006;48(3):181–190.
- Całkosiński I. The influence of tocopherol on diagnostic indexes of inflammatory reaction in rats undergoing dioxin exposition [habilitation thesis]. Wrocław, Poland: Wroclaw Medical University; 2008.
- Całkosiński I. The course of experimentally induced acute pleuritis with use of nitrogranulogen (NTG) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [habilitation thesis]. Wrocław, Poland: Wroclaw Medical University; 2005.
- Moon BH, Hong CG, Kim SY, et al. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain. Toxicol Appl Pharmacol. 2008;233:314–422.
- Lensu S, Miettinen R, Pohjanvirta R, Lindén J, Tuomisto J. Assessment by c-Fos immunostaining of changes in brain neural activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leptin in rats. Basic Clin Pharmacol Toxicol. 2006;98:363–371.
- Li X, Johnson DC, Rozman KK. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrous cyclicity and ovulation in female Sprague-Dawley rats. Toxicol Lett. 1995;78:219–222.
- Sonne C, Leifsson PS, Dietz R, et al. Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursus maritimus). Environ Sci Technol. 2006;40:5668–5674.
- Verreault J, Norstrom RJ, Ramsay MA, Mulvihill M, Letcher RJ. Composition of chlorinated hydrocarbon contaminants among major adipose tissue depots of polar bears (Ursus maritimus) from the Canadian high Arctic. Sci Total Environ. 2006;370:580–587.
- Jin MH, Hong CH, Lee HY, Kang HJ, Han SW. Enhanced TGF-beta1 is involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress in C57BL/6 mouse testis. Toxicol Lett. 2008;178:202–209.
- Kakeyama M, Sone H, Tohyama C. Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring. J Endocrinol. 2008;197:351–358.
- Delwing D, Tagliari B, Chiarani F, Wannmacher CM, Wajner M, Wyse AT. Alpha-tocopherol and ascorbic acid administration prevents the impairment of brain energy metabolism of hyperargininemic rats. Cell Mol Neurobiol. 2006;26:177–189.
- Kloser E, Böhmdorfer S, Brecker L, et al. Synthesis of 5-(fluorophenyl)tocopherols as novel dioxin receptor antagonists. Eur J Org Chem. 2011;2011:2450–2457.
- Norazlina M, Lee PL, Lukman HI, Nazrun AS, Ima-Nirwana S. Effects of vitamin E supplementation on bone metabolism in nicotine-treated rats. Singapore Med J. 2007;48:195–199.
- Gong N, Zhang M, Zhang X-B, Chen L, Sun GC, Xu TL. The aspirin metabolite salicylate enhances neuronal excitation in rat hippocampal CA1 area through reducing GABAergic inhibition. Neuropharmacology. 2008;54:454–463.
- Lu YG, Tang ZQ, Ye ZY, et al. Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha1-subunits. Br J Pharmacol. 2009;157:1514–1522.
- Całkosiński I, Gamian A, Dobrzyński M. Possibilities of the use of tocopherol in the case of intoxication with dioxins. In: Żuber M, ed. Natural and Civilization Catastrophes, the dangers and challenges for the global gecurity. Wrocław: The Tadeusz Kościuszko Land Forces Military Academy Publishing House; 2009:275–284.
- Fatokun AA, Stone TW, Smith RA. Cell death in rat cerebellar granule neurons induced by hydrogen peroxide in vitro: Mechanisms and protection by adenosine receptor ligands. Brain Res. 2007;1132:193–202.
- Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004;23:9247–9258.