Tocopherol Enhances the Antioxidant Defense System and Histomorphometric Parameters in The Gastrointestinal Tract of Rats Treated with Sodium Arsenite
Click to view file (PDF)

How to Cite

Oladokun, O., Olaleye, T., Moses, N., Oladosu, O., Babatunde, A., Adedokun, K., Owonikoko, M., & Ajeigbe, K. (2022). Tocopherol Enhances the Antioxidant Defense System and Histomorphometric Parameters in The Gastrointestinal Tract of Rats Treated with Sodium Arsenite. Nigerian Journal of Physiological Sciences, 37(1), 83–92.


Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown.  Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure. Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer’s patches in the intestines, which are all lessened with tocopherol treatment.  These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract.

Keywords: Tocopherol, arsenic, stomach, ileum, colon
Click to view file (PDF)


Adebayo-Gege GI, Salami AT, Odukanmi AO, Omotosho IO, Olaleye SB. (2018) Pro-ulcerogenic activity of sodium arsenite in the gastric mucosa of male Wistar rats. Journal of African Association of Physiological Sciences. 6(2):95-103.

Ajeigbe KO, Onifade AA, Omotoso DR, Enitan SS, Olaleye SB. (2014) Anti-ulcerogenic activity of Aspilia africana leaf extract: roles of gastric acid, oxidative stress and neutrophil infiltration. Afr J Biomed Res.17(3):193-201.

Anselm OH, Cavoura O, Davidson CM, Oluseyi TO, Oyeyiola AO, and Togias K. (2021) Mobility, spatial variation and human health risk assessment of mercury in soil from an informal e-waste recycling site, Lagos, Nigeria. Environ Monitor Assess. 193(7):1-13.

Asante KA, Agusa T, Biney CA, Agyekum WA, Bello M, Otsuka M, Itai T, Takahashi S, Tanabe S. (2012) Multi-trace element levels and arsenic speciation in urine of e-waste recycling workers from Agbogbloshie, Accra in Ghana. Sci. Total Environ. 424, 63–73.

Chau ND, Sebesvari Z, Amelung W, Renaud FG. (2015) Pesticide pollution of multiple drinking water sources in the Mekong Delta, Vietnam: evidence from two provinces. Environ Sci Pollut Res.;22(12):9042-58.

Chen C, Quian Y, Chen Q, Li C. (2011) Assessment of daily intake of toxic elements due to consumption of vegetables, fruits, meats, and seafood by inhabitants of Xiamen, China. J. Food Sci.; 76, 181-188.

Chih-Hung L, Wei-Ting L, Hsin-Su Y. (2010) Mechanisms and immune dysregulation in arsenic skin carcinogenesis. Journal of Cancer Therapy. 29:2010

Chiocchetti GM, Vélez D, Devesa V. (2018) Effect of subchronic exposure to inorganic arsenic on the structure and function of the intestinal epithelium. Toxicology letters. 286:80-8.

Chiocchetti GM, Vélez D, Devesa V. (2019) Effect of chronic exposure to inorganic arsenic on intestinal cells. Journal of Applied Toxicology. 39(6):899-907.

Claiborne A. Catalase activities. In: Greewald AR editor. (1995) Handbook of methods for oxygen Radical research. Florida: CRC Press: 237-242.

Drobná Z, Jaspers I, Thomas DJ, Stýblo M. (2003) Differential activation of AP‐1 in human bladder epithelial cells by inorganic and methylated arsenicals. The FASEB Journal. 17:67-9.

Flora SJ, Mittal M, Mehta A. (2008) Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res. 128(4):501.

Guide for the Care and Use of Laboratory Animals in Biomedical and Behavioral Research In: Veterinary-Medical Care Manual. (1996) Institute for Laboratory Animal Research, American Academy of Sciences, Washington. Pp. 56–70

Habig WH, Pabst MJ, Jakoby WB. (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem. 249(22):7130-9.

Hemalatha P, Reddy AG, Rani MU, Anandkumar A, Shivakuma P. (2013) Arsenic-induced histological alterations in various organs in rats. Int J Life Sci Biotechnol Pharm Res. 2(1):119-27.

Ibe FC, Opara AI, Ibe BO, Adindu BC, Ichu BC. (2018) Environmental and health implications of trace metal concentrations in street dusts around some electronic repair workshops in Owerri, Southeastern Nigeria. Environ Monitor Assess. 190(12):1-2.

Ighodaro OM, Akinloye OA. (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 54(4):287-93.

Jiang Q. (2014) Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Rad Biol Med. 72:76-90.

Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacol. 11(3):151-69.

Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M. (2011) Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol. 31(2):95-107.

Kamada Y, Jenkins GJ, Lau M, Dunbar AY, Lowe ER, Osawa Y. (2005) Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 142:19–27.

Kamisah Y, Qodriyah HM, Chua KH, Nur Azlina MF. (2014) Vitamin E: A potential therapy for gastric mucosal injury. Pharm Biol. 52(12):1591-7.

Karkarna MZ and Matazu MA. (2021) Evaluation of Heavy metals pollution around Kano municipal solid waste Dumpsites, Kano state, Nigeria. UJMR 6: pp 146 – 152.

Khan A, Sharaf R, Zargham Khan M, Kashif Saleemi M, Mahmood F. (2013) Arsenic Toxicity in Broiler Chicks and its Alleviation with Ascorbic Acid: A Toxico-patho-biochemical Study. Inter J Agric Biol. 15(6): 1105-1107.

Kiddee P, Naidu R, Wong MH, Hearn L, Muller JF. (2014) Field investigation of the quality of fresh and aged leachates from selected landfills receiving e-waste in an arid climate. Waste Manag.; 34, 2292–2304.

Kim JJ, Shajib MS, Manocha MM, Khan WI. (2012) Investigating intestinal inflammation in DSS-induced model of IBD. JoVE . 60: e3678.

Kitchin KT and Kirk T. (2001) Recent advances in arsenic carcinogenesis: Modes of action, animal model systems, and methylated arsenic metabolites. Toxicol. Appl. Pharmacol. 172:249-261.

Mass MJ, Tennant A, Roop BC, Cullen WR, Styblo M, Thomas DJ, Kligerman AD. (2001) Methylated trivalent arsenic species are genotoxic. Chem Res Toxicol. 14:355-61.

Misra, H.P. and Fridovich, I. (1972) The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. J Biol Chem. 247:3170-3175.

Mo J, XiaY, WadeTJ, Schmitt M, Le XC, Dang R, Mumford JL. (2006) Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium, and skin hyperkeratosis in inner mongolia. Environ. Health Perspect. 114:835–841.

Nachman KE, Baron PA, Raber G, Francesconi KA, Navas-Acien A, Love DC. (2013) Roxarsone, inorganic arsenic, and other arsenic species in chicken: a US-based market basket sample. Environmental Health Perspectives.121(7):818-24.

Olafisoye OB, Adefioye T, Osibote OA. (2013) Heavy Metals Contamination of Water, Soil, and Plants around an Electronic Waste Dumpsite. Pol J Environ Studies. 22(5):1431-1439

Olaleye SB, Adaramoye OA, Erigbali PP, Adeniyi OS. (2007) Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats. World J Gastroenterol. 13(38):5121.

Petrick JS, Ayala-Fierro F, Cullen WR, Carter DE, Aposhian HV. (2000) Monomethylarsonous acid (MMAIII) is more toxic than arsenite in Chang human hepatocytes. Toxicol Appl Pharmacol;163(2):203-7.

Popoola LT, Yusuff AS, Aderibigbe TA. (2019) Assessment of natural groundwater physico-chemical properties in major industrial and residential locations of Lagos metropolis. Applied Water Science. 9(8):1-0.

Pradhan JK, Kumar S. (2014) Informal e-waste recycling: Environmental risk assessment of heavy metal contamination in Mandoli industrial area, Delhi, India. Environ. Sci. Pollut. Res. Int.; 21, 7913–7928.

Reboul E. (2017) Vitamin E bioavailability: mechanisms of intestinal absorption in the spotlight. Antioxidants. 6(4):95-100.

Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra W. (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science. 179(4073):588-90.

Singh AP, Goel RK, Kaur T. (2011) Mechanisms pertaining to arsenic toxicity. Toxicol Inter.;18(2):87.

Smith AH, Lingas EO, Rahman M. (2000 ) Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bulletin of the World Health Organization. 78:1093-103.

Somé I, Sakira A, Ouédraogo M, Ouédraogo T, Traoré A, Sondo B, Guissou P. (2012) Arsenic levels in tube-wells water, food, residents' urine and the prevalence of skin lesions in Yatenga province, Burkina Faso. Interdisc Toxicol.5(1):38-41.

Stýblo M, Drobná Z, Jaspers I, Lin S, Thomas DJ. (2002) The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect. 110(suppl 5):767-71.

Szymanska-Chabowska A, Antonowicz-Juchniewicz J. Andrzejak R. (2002) Some aspects of arsenic toxicity and carcinogenicity in living organism with special regard to its influence on cardiovascular system, blood and bone marrow. Int. J. Occup. Med. Environ. Health. 15:101–116.

Traber MG and Arai H. Molecular mechanisms of vitamin E transport. (1999) Annual Review of Nutrition. 19:343-355.

Van Zuidewijn DD, Schillings PH, Wobbes TH, Hendriks T, de Boer HH. (1992) Morphometric analysis of the effects of antineoplastic drugs on mucosa of normal ileum and ileal anastomoses in rats. Expt Mol Pathol. 56(2):96-107.

Varshney R, Kale RK. (1990) Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. Inter J Rad Biol. 58(5):733-43.

World Health Organization, (2012). Arsenic. Fact sheet no. 372.

Xia Y, Zweier JL. (1997) Measurement of myeloperoxidase in leukocyte-containing tissues. Anal Biochem. 245(1):93-6.

Yamanaka K, Hasegawa A, Sawamura R, Okada S. (1991) Cellular response to oxidative damage in lung induced by the administration of dimethylarsinic acid, a major metabolite of inorganic arsenics, in mice. Toxicol Appl Pharmacol. 108(2):205-13.

Yousef MI, El-Demerdash FM, Radwan FM. (2008) Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin. Food Chem Toxicol.46 (11):3506-3511.

Creative Commons License

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

Copyright (c) 2022 Nigerian Journal of Physiological Sciences