Aquoeus Extracts of Daucus Carota (Linn) Protected the Postnatal Developing Cerebellum of Wistar Rats Against Arsenic-Induced Oxidative Stress

Abstract

The neuroprotective effects of the aqueous extract of Daucus carota (Dc) tuber against arsenic-induced oxidative damage on the developing cerebellum of Wistar rats were studied. Twenty-five pregnant rats (110-200g) were divided into five groups (n=5) – control received distilled water; Arsenic (As); Dc (200mg/kg); Dc (200mg/kg) +As; Vitamin C (Vc) (100mg/kg) +As. The pregnant rats in all the groups were treated orally from the first day of pregnancy to postnatal day 21. The Dc extract and Vc were administered one hour before the administration of As. Body weight of the pups on days 1, 7, 14, 21 and 28 were recorded, while neurobehavioural (forelimb grip strength and negative geotaxis) tests were done on day 21 pups. The rats were sacrificed and cerebellar tissues were collected for oxidative stress, histological (H and E), and immunohistochemical studies. Decreased forelimb grip strength, increased lipid peroxidation and decreased glutathione, glutathione peroxidase, catalase and superoxide dismutase was observed in the As group compared with the control and other treated groups. Histologically, the cerebellar cortex of the As pups showed persistent external granular layer (EGL) on postnatal day 21, reduced thickness of the molecular layer (ML) on postnatal day 28, pyknotic and depleted Purkinje cells compared with the control and other treated rats. Immunohistochemical evaluations of the cerebellar cortex showed astroliosis in the As-treated group on day 21 pups compared with the control and other treated groups.  Aqueous extracts of Daucus carota and Vitamin C reversed the toxicity caused by arsenic. From the results of the study, arsenic-induced oxidative stress with morphological alterations in the perinatal developing rat cerebellum. Extracts of Daucus carota exhibited antioxidant activity as such may be a potential neuroprotective agent.

Click to view file (PDF)

References

Ajibade, A.J., Fakunle, P.B., and Shittu, O.R. (2015). Neuroprotective effect of aqueous extract of Garcinia kola on monosodium glutamate-induced cerebellar cortical damage in adult Wistar rats. Eur J Med Plants; 5 (1): 13-22.

Alarcón-Flores, M. I., Romero-Gonzālez, R., Martinez vidal, J. L., and Frenich, A. G., 2015. Systematic study of the content of phytochemicals in fresh and fresh-cut vegetables. Antiox; 4: 345-358.

Altman, J. and Bayer, S.A. (1985). Embryonic development of the rat cerebellum I. delineation of the cerebellar primordium and early cell movements. J Comp Neurol; 231: 1-26.

Aung, K.H., Kyi-Tha-Thu, C., Kazuhiro, S., Nakamura, K., Tanoue, A., Nohara, K., Kakeyama, M., Tohyama, S. ., and Maekawa, F. (2016). Prenatal exposure to arsenic impairs behavioural flexibility and cortical structure in mice. Front Neurosci-Switz; 10: 137.

Avani, G., and Rao, M. . (2009). Toxicological effects of arsenic and its modulation by vitamin A in the brain and blood of Swiss albino mice. Toxicol Environ Cheml; 91(1): 65–74.

Balaei, M.R., Ashtari, N., and Bergen, H. (2017). The Embryology and Anatomy of the cerebellum. Development of the cerebellum from molecular aspects to diseases Contemp clin Neurosci: 33-43.

Barai, M., Ahsan, N., Nilanjana, P., Hossain, K., Rashid, M.A., Kato, M., Ohgami, N., and Akhand, A.A. (2017). Amelioration of arsenic-induced toxic effects in mice by dietary supplementation of Syzygium cumini leaf extract. Nagoya J Med Sci; 79: 167-177.

Bashir, S., Sharma, Y., Irshad, M., Gupta S.D., and Dogra, T.D. (2006). Arsenic-induced cell death in liver and brain of experimental rats. Basic Clin Pharmacol Toxicol; 98: 38-43.

Benedetti, J. (1996). Arsenic. Centre de Toxicologie du Québéc. Centre Hospitailer Universitaire de Québéc (CHUQ).

Betteridge, D.J. (2000). What is oxidative stress? Metab; 49(2): 3-8.

Beutler, E., Duron, O., and Kelly, B.M. (1963). Improved method for the determination of blood glutathione. J Lab Clin Med; 61: 882–888.

Bikashvili, T., Lordkipanidze, T., Gogichaishvili, N. and Pochkhidze, N. (2017). Effect of arsenic exposure on behaviour of rats of various age groups. Georgian Med News; 264: 119-126.

Bjarnadotti, A. (2015). Carrots 101: Nutrition facts and health benefits. Authority Nutr; newsletter, issue 3.

Bonetto, J.G., Villaamil-Lepori, E. and Puntarulo, S. (2017). Oxidative balance in brain after exposure to arsenic in ex vivo and in vivo models. Int J Adv Res; 5(10): 41-50.

Buckner, R.L. (2013). The cerebellum and cognitive functions: 25 years of insight from anatomy and neuroimagaing. Neuron; 80(£): 807-815.

Butts, T., Green, M.J. and Wingate, R.J.T. (2014). Development of the cerebellum: simple steps to make a small brain. Dev;, 141: 4031-4041.

Bystrickā, J., Kavalcovā, P., Musilovā, J., Vollmannovā, A., Tóth, T. and Lenkovā, M. (2015). Carrot (Daucus carota L. ssp sativus (Hoffm.) Arcang.) as source of antioxidants. Acta Agric Slov; 304-311.

Catanzaro, I., Schiera, G., Sciandrello, G., Barbata, G., Caradonna, F., Proia, P. and Di Liegro, I. (2010). Biological effects of inorganic arsenic on primary cultures of rat astrocytes. Int J Mol Med; 26: 457-462.

Chen, P., Miah, M.R. and Aschner, M. (2016). Metals and neurodegeneration. F1000 Research 2016, 5 (F1000 Faculty Rev); 366: 1-13.

Chistulo, L. (2017). Arsenic. WHO. Retrieved June 2018.

Claiborne, A., 1985. Catalase activity. In: Handbook of methods for oxygen radical research (R.A. Greenwald, Ed). Boca Raton, FL, pp.283-284.

Ding, X., Su, Q., Jiang, M., Xie, H., Cong, J. and Wang, L. (2013). Arsenic effects on cerebellar development of mice. Toxicol Mech Methods; 23(9): 672–677.

Egbinola, C.N. and Amanambu, A.C. (2014). Ground water contamination in Ibadan, south-west Nigeria. SpringerPlus; 3(448): 1-6.

El-Masry, S. and El-Rhman, A.A. (2017). The protective effect of beetroot and carrot juices on doxorubicin-induced cardiac injury and associated inflammatory response. WJPPS; 6(12): 109-126.

Etim, E.U. (2017). Occurrence and distribution of arsenic, antimony, and selenium in shallow ground water systems of Ibadan metropolis, south-western Nigeria. JH&P; 7(13): 32-41.

Ettinger, A.S., Arbuckle, T.E., Fisher, M., Liang, C.L., Davis, K., Cirtiu, C., Bélanger, P., LeBlanc, A., Fraser, W.D. and the MIREC Study Group (2017). Arsenic levels among pregnant women and new-borns in Canada: Results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. Environ Res; 153: 8–16.

Gandhi, S. and Abramov, A.Y. (2012). Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev; 2012: 1-11.

Gandhi, D.N. and Panchal, G.M. (2011). Effects of low level arsenic exposure on the development of neurobehavioural toxicity in rats. Res J Environ Toxicol; 5(6): 348-358.

Grosicki, A. and Kowalski, B. (2006). Retention of Selenium in Rats exposed to Vitamin C. Bull Vet Inst Pulawy; 50: 387-389.

Hall, A., McLeod, A., Counsell, C., Thomson, L. and Mutch, L. (1995). School attainment, cognitive ability and motor function in a total Scottish very-low-birth weight population at eight years: a controlled study. Dev Med Child Neurol; 37: 1037–50.

Halliwell, B., and Whiteman, M. (2004). Measuring reactive species and oxidative damage in vivo and in cell culture: How you should do it and what do the results mean? Br J Pharmacol; 142: 231-255.

Hashimoto, M. and Hibi, M. (2012). Development and evolution of cerebellar neural circuits. Dev Growth Differ; 54: 373-389.

Heinsen, H. (1977). Quantitative anatomical studies on the postnatal development of the cerebellum of the Albino rat. Anat Embryol; 151: 201-218.

Herrera, A., Pineda, J. and Antonio, M.T. (2013). Toxic effects of perinatal arsenic exposure on the brain of developing rats and the beneficial role of natural antioxidants. Environ Toxicol Pharmacol; 36: 73–79.

Hill R.A., Li A.M. and Grutzendler J. (2018). Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat Neurosci; 21@ 683–695.

Htway, S., Sein, M., Nohara, K. and Win-Shwe, T. (2019). Effects of developmental arsenic exposure on the social behaviour and related gene expression in C3H adult male mice. Int J Environ Res Public Health; 16(174): 1-12.

Imosemi, I.O. and Osinubi, A.A. (2011). Phenytoin-induced toxicity in the postnatal developing cerebellum of Wistar rats, effects of Calotropis procera on histomorphometric parameters. Int J Morphol; 29(2): 331-338.

Ince, S., Kucukkurt, I., Turkmen, R., Demirel, H. H. and Sever, E. (2012). Dietary Yucca schidigera supplementation reduces arsenic-induced oxidative stress in Swiss albino mice. Toxicol Ind Health; 29(10): 904–914.

Izah, S.C., and Srivastav, A.L. (2015). Level of arsenic in potable water sources in Nigeria and their potential health impacts: A review. J Environ Treat Tech; 2(1): 15-24.

Khodayar, M.J., Kalantari, H., Samimi, A., Alboghobeish, S., Moghadam, P.T., Zeinvand-lorestani, M. (2019). Arsenic and oxidative stress in pentylenetetrazole-induced seizures in mice. J Basic Clin Pathophy; 7(1): 1-6.

Kile, M.L., Cardenas, A., Rodrigues, E., Mazumdar, M., Dobson, C., Golam, M., Quamruzzaman, Q., Rahman, M. and Christiani, D.C. (2016). Estimating Effects of Arsenic Exposure during Pregnancy on Perinatal Outcomes in a Bangladeshi Cohort. Epidemiology; 27 (2): 173–181.

Kozul-Horvath, C.D., Zandbergen, F., Jackson, B.P., Enelow, R.I. and Hamilton, J.W. (2012). Effects of Low-Dose Drinking Water Arsenic on Mouse Foetal and Postnatal Growth and Development. PLoS ONE; 7 (5): e38249.

Lee, H., Park, Y.K. and Kang, M. (2011). The effect of carrot juice, β-carotene supplementation on lymphocyte DNA damage, erythrocyte antioxidant enzymes and plasma lipid profiles in Korean smoker. Nutr Res Pract; 5(6): 540-547.

Lopez, I.A., Acuna, D., Beltran-Parrazal, L., Lopez, I.E., Amarnani, A., Cortes, M. and Edmond, J. (2009). Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air). BMC Neurosci; 10:53.

Ma, N., Sasoh, M., Kawanishi, S., Sugiura, H. and Piao, F. (2010). Protection effect of taurine on nitrosative stress in the mice brain with chronic exposure to arsenic. J Biomed Sci; 17(1): 1-6.

Malomo, A.O., Imosemi, I.O., Osuagwu, F.C., Oladejo, O.W., Akang, E.E.U. and Shokunbi, M.T. (2004). Histomorphometric studies on the effect of cyanide consumption of the developing cerebellum of Wistar rats (Rattus Novergicus). WAJM; 23(4): 323-328.

Mani, V., Parle, M., Ramasamy, K. and Majeed, A.A. (2010). Anti-dementia potential of Daucus carota seed extracts in rats. Pharmacologyonline; 1: 552-565.

Manto, M., Bower, M.J., Conforto, A.B., Delgado-García, J.M., Farias da Guarda, S.N., Gerwig, M., Habas, C., Hagura, N., Ivry, R.B., Mariën, P., Molinari, M., Naito, E., Nowak, D.A., Taib, N.O.B., Pelisson, D., Tesche, C.D., Tilikete, C. and Timmann, D. (2012). Consensus Paper: Roles of the Cerebellum in Motor Control—The Diversity of Ideas on Cerebellar Involvement in Movement. Cerebellum; 11:457–487.

McKay, B.E. and Turner, R.W. (2005). Physiological and morphological development of the rat cerebellar Purkinje cell. J Physiol; 567(3): 829-850.

Milton, A.H., Smith, W., Rahman, B., Hasan, Z., Kulsum, U., Dear, K., Rakibuddin, M. and Ali, A. (2005). Chronic Arsenic Exposure and Adverse Pregnancy Outcomes in Bangladesh. Epidemiology; 16(1): 82-86.

Minai, M. (2014). Purkinje cells. The embryo project encyclopaedia. ISSN: 1940-5030.

Misra, H.P. and Fridovish, I. (1972). The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem; 247(10):3170-3175.

Mortz, B.A. and Alberts, J.R. (2005). The validity and utility of geotaxis in young rodents. Neurotoxicol Teratol; 27: 529-533.

Mundey, M.K., Roy, M., Roy, S., Awasthi, M.K. and Sharma, R. (2013). Antioxidant Potential of Ocimum sanctum in Arsenic Induced Nervous Tissue Damage. Braz J Vet Pathol; 6(3): 95 – 101.

Nagar, A., Sharma, V. and Chhipa, A.S. (2017). Roles of antioxidants in biological system: a review. Mintage J Pharma Med Sci; 6(1): 7-12.

Nayeem, K., Godad, A., Hashilkar, N., and Joshi, R.K. (2010). Gastroprotective activity of the aqueous extract of Daucus carota L. in rats. IJRAP; 1(1): 112-119.

Negishi, T., Matsunaga, Y., Kobayashi, Y., Hirano, S. and Tashiro, T. (2013). Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behaviour, and Decreased Cerebellar Glutathione Concentration in Rats. Toxicol Sci; 136(2): 478–486.

Odebunmi, E.O., Olutona, G.O., Akintunde, E.A., Faboro, E.O., Balogun, O.S. and Olawaniyi, O.O. (2014). Trace metal levels of drinking water sources in parts of Osun state, Nigeria. EJESM; 7(6): 635-644.

Okey, S.M. and Ayo, J.O. (2015). The role of co-administration of ascorbic acid and zinc gluconate on brain biochemical changes in Wistar rats during hot humid season. European J Biotechnol Biosci; 3(1): 46-52.

Onanuga O.I., Ridwan, I.B., Olaiya, O.G., Abdulbasit, A., Jaji-Sulaimon O.R., Roehan, F.O. and Abass, S.A. (2013). Effects of ascorbic acid on immunosuppressive drug-azathioprine-induced alteration in the liver and kidney of adult wistar rats [Rattus norvegicus]. Euro J Exp Bio; 3(2):371-378.

Piao, F., Ma, N., Hiraku, Y., Murata, M., Oikawa, S. and Yokoyama, K. (2005). Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels. J Occup Health; 47: 445-449.

Potter, A.S., Foroudi, S., Stamatikos, A., Patil, B.S. and Deyhim, F. (2011). Drinking carrot juice increases total antioxidant status and decreases lipid peroxidation in adults. Nutr J; 10(96): 1-6.

Prajna, A.S. and Hedge, K. (2018). Pharmacological health benefits of Daucus carota: A review. Int J Pharma Chem Res; 4(2): 77-82.

Punshon, T., Davis, M.A., Marsit, C.J., Theiler, S.K., Baker, E.R., Jackson, B.P., Conway, D.C. and Karagas. M.R. (2015). Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort. J Expo Sci Environ Epidemiol; 1-5.

Rahman, A., Vahter, M., Ekström, E., Rahman, M., Haider, A., Mustafa, M.G., Wahed, M.A., Yunus, M. and Persson, L. (2007). Association of Arsenic Exposure during Pregnancy with Foetal Loss and Infant Death: A Cohort Study in Bangladesh. Am J Epidemiol; 165(12): 1389–1396.

Rahman, A., Vahter, M., Smith, A.H., Nermell, B., Yunus, M., El Arifeen, S., Persson L. and Ekström, E. (2008). Arsenic Exposure during Pregnancy and Size at Birth: A Prospective Cohort Study in Bangladesh. Am J Epidemiol; 169(3): 304-312.

Rao, M.V. and Avani, G. (2004). Arsenic induced free radical toxicity in brain of mice. IJEB; 42: 495-498.

Rodríguez, V.M., Carrizales, L., Mendoza, M.S., Fajardo, O.R. and. Giordano, M. (2002). Effects of sodium arsenite exposure on development and behaviour in the rat. Neurotoxicol Teratol; 24: 743–750.

Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D.G. and Hoekstra, W.G. (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science; 179(4073):588-590.

Silva Dias, J.C. (2014). Nutritional and health benefits of carrots and their seed extracts. Food Nutr Sci; 5: 2147-2156.

Singh, K., Singh, N., Chandy, A. and Manigauha A. (2012). In vivo antioxidant and hepatoprotective activity of methanolic extracts of Daucus carota seeds in experimental animals. Asian Pac J Trop Biomed; 2(5): 385–388.

Sodimbaku, V., Pujari, L., Mullangi, R. and Marri, S. (2016). Carrot (Daucus carota L.): nephroprotective against gentamicin-induced nephrotoxicity in rats. Ind J Pharmacol; 48(2): 122-127.

Sodini, J. (2015). 12 major neurotoxins that affect our brain. Online newspaper article, downloaded June, 2018.

Tamashiro, K.L.K., Wakayama, T., Blanchard, R.J., Blancgard, C. and Yanagimachi, R. (2000). Postnatal growth and behavioural development of mice cloned from adult cumulus cells. Bioreprod; 63: 328-334.

Tolins, M., Ruchirawat, M. and Landrigan, P. (2014). The Developmental Neurotoxicity of Arsenic: Cognitive and Behavioural Consequences of Early Life Exposure. Ann Global Health; 80: 303-314.

Tyler, C.R. and Allan, A.M. (2014). The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: A review. Curr Envir Health Rpt; 1:132-147.

UNICEF-WHO, 2018. Arsenic Primer. Guidance on the investigation and mitigation of arsenic contamination.

Vashney, R. and Kale, R. K., 1990. Effects of calmodulin antagonist. Int J Radiat Biol; 58:733-743.

WHO, 2017. Guidelines for drinking-water quality: fourth edition incorporating the first addendum. ISBN 978-92-4-154995-0.

Yuan, L., Liu, J., Zhen, J., Xu, Y., Chen, S., Van Halm-Lutterodt, N. and Xiao, R. (2017). Vegetable and fruit juice enhances antioxidant gene expression in rat liver, brain and colon. Genetics Mol Bio; 40(1): 134-141.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2022 Nigerian Journal of Physiological Sciences