Toxicology International (Formerly Indian Journal of Toxicology)

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Modulatory Role of Kolaviron (KV), a Biflavonoid from Garcinia kola, in Sodium Arsenite-Induced Hepatotoxicity and Haematotoxicity in Rats


Affiliations
1 Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
2 Department of Veterinary Medicine, University of Ibadan, Nigeria
     

   Subscribe/Renew Journal


Arsenic acid (NaAsO2) is an environmental pollutant that is widely distributed in air, water and soil. Exposure to this silent killer in drinking water has posed a major health threat to both developing and developed countries of the world. The use of phytochemicals has gained acceptance in the recent years. Hence, the purpose of this study was to explore the chemopreventive effect of Kolaviron, a biflavonoid from Garcinia kola seed on NaAsO2 induced hepatoxicity and haematotoxicity. Rats were pre-treated with KV (100&amp;200mg/kg) for 7 days prior to NaAsO2 (10mg/kg; i.p.) intoxication on day 8. Complete blood counts (CBC), liver function tests, hepatic antioxidant, markers of oxidative stress and histological sections of the liver were assessed. NaAsO2 intoxication caused a significant (p<0.05) increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Also, the hepatic catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) content were significantly (p<0.05) reduced whereas markers of oxidative stress such as malondialdehyde (MDA), hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also severely (p<0.05) elevated. NaAsO2 intoxication caused a significant (p<0.05) reduction in packed cell volume (PCV), red blood cell (RBC) counts and haemoglobin (Hb) concentration. KV pre-treatment significantly suppressed markers of oxidative stress and prevented the depletion of antioxidant defence system. Normochromic normocytic anaemia precipitated by NaAsO2 intoxication was attenuated by KV administration. Histopathological examination showed that liver tissue injury mediated by arsenic was ameliorated by KV pre-treatment. It was concluded that KV may represent a potential drug candidate to protect against liver damage and other detrimental effects of arsenic toxicity.

Keywords

Hepatotoxicity, Arsenite, Kolaviron (KV), Oxidative Stress, Chemoprevention.
User
Subscription Login to verify subscription
Notifications
Font Size

  • Meliker JR, Wahl RL, Cameron LL, Nriagu JO. Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: A standardized mortality ratio analysis. Environ Health 2007; 6:4.

  • Tapio S, Grosche B. Arsenic in the aetiology of cancer. Mutat Res 2006; 612: 215-46.

  • Liu J, Waalkes MP. Liver is a target of arsenic carcinogenesis. Toxicol Sci 2008; 105:24- 32.

  • Wu J, Liu J, Waalkes MP, Cheng ML, Li L, Li CX, et al.. High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Exp Biol Med (Maywood) 2008; 233: 377-384.

  • Mazumder DN. Effect of chronic intake of arsenic-contaminated water on liver. Toxicol Appl Pharmacol 2005; 206: 169-75.

  • Xu Y, Wang Y, Zheng Q, Li B, Li X, Jin Y, et al. Clinical manifestations and arsenic methylation after a rare subacute arsenic poisoning accident. Toxicol Sci 2008; 103: 278-84.

  • Wang Y, Xu Y, Wang H, Xue P, Li X, Li B, et al. Arsenic induces mitochondria-dependent apoptosis by reactive oxygen species generation rather than glutathione depletion in Chang human hepatocytes. Arch Toxicol 2009; 83: 899-908.

  • Abarikwu SO, Farombi EO, Pant AB. Kolaviron biflavanoids of Garcinia kola seeds protect atrazine-induced cytotoxicity in primary cultures of rat Leydig cells. Int J Toxicol 2012; 31: 407-15.

  • Farombi EO, Adedara IA, Akinrinde SA, Ojo OO, Eboh AS. Protective effects of Kolaviron and quercetin on cadmiuminduced testicular damage and endocrine pathology in rats. Andrologia 2012; 44: 273-84.

  • Igado OO, Olopade JO, Adesida A, Aina OO, Farombi EO. Morphological and biochemical investigation into the possible neuroprotective effects of Kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium. Drug Chem Toxicol 2012; 35: 371-80.

  • Adedara IA, Daramola YM, Dagunduro JO, Aiyegbusi MA, Farombi EO. Renoprotection of Kolaviron against benzo (A) pyrene-induced renal toxicity in rats. Ren Fail 2015; 23: 1-8.

  • Adedara IA, Farombi EO. Influence of Kolaviron and vitamin E on ethylene glycol monoethyl ether-induced haematotoxicity and renal apoptosis in rats. Cell Biochem Funct. 2014a; 32: 31-38

  • Adedara IA, Farombi EO. Kolaviron protects against ethylene glycol monoethyl ether-induced toxicity in boar spermatozoa. Andrologia 2014b; 46: 399-407.

  • Owoeye O, Adedara IA, Bakare OS, Adeyemo OA, Egun C, Farombi EO. Kolaviron and vitamin E ameliorate hematotoxicity and oxidative stress in brains of Prepubertal rats treated with an anticonvulsant phenytoin. Toxicol Mech Methods 2014; 24: 353-61.

  • Adedara IA, Mathur PP, Farombi EO. Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins, Fas/Fas-L and caspases expressions in rats. Toxicol Mech Methods 2013; 23: 689-96.

  • Farombi EO, Adedara IA, Ajayi BO, Ayepola OR, Egbeme EE. Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium- induced colitis in rats. Basic Clin Pharmacol Toxicol 2013; 113: 49-5.

  • Iwu MM, Igboko OA, Onwuchekwa U, Okunji CO. Evaluation of the anti- hepatotoxicity of the biflavonoids of Garcinia kola seeds. J Ethnopharmacol 1987; 21: 27-142.

  • PHS (PUBLIC HEALTH SERVICE) . Public health service policy on humane care and the use of laboratory animals. US Department of Health and Humane services, Washington, DC, 1996; pp. 99-158.

  • Wolff SP. Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Method Enzymol 1994;. 233: 182-89.

  • Varshney R, Kale RK. Efect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes Int J Biol 1990; 158: 73-741.

  • Shinha KA. Colorimetric assay of Catalase. Anal Biochem 1972; 47: 389-94.

  • Misra HP, Fridovich I. The role of superoxide anoin in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 217:3170-3175.

  • Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola, O. Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 2015; 30: 1235-43.

  • Omobowale TO, Oyagbemi AA, Akinrinde AS, Saba AB, Daramola OT, Ogunpolu BS, et al. Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats. Environ Toxicol Pharmacol 2014; 37: 1202-11.

  • Buetler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882-88.

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzeneinduced liver necrosis; protective role of GSH & evidence for 3, 4 bromobenzene oxide as the hepatotoxic metabolite. JB lippinocott 1994; 108-144.

  • Habig WH, Pabst MJ, Jacoby W. Glutathione-S-transferase Activity: The Enzymic step in Mercapturic Acid formation. J Biol Chem 1974; 249: 130-39.

  • Olaleye SB, Adaramoye OA. Erigbali PP, Adeniyi OS. Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats. World J Gastroenterol 2007; 13: 5121-26.

  • Gornal AG, Bardawill JC, David MM. Determination of serum proteins by means of Biuret reaction. J Biol Chem 1949; 177: 751-66.

  • Jain NC. Schalm’s Veterinary Haematology, 4th Ed. Lea and Febiger, Philadelphia, U.S.A. 4th Ed. Lea and Febiger, Philadelphia, U.S.A. 1986.

  • Drury RA, Wallington EA, Cancerson R. Carlton’s Histopathological Techniques, fourth ed. Oxford University Press, Oxford, London, New York. 1976.

  • Antonio GMT, Herrera DA, Pineda PJ. Hematological effects of arsenic in rats after subchronical exposure during pregnancy and lactation: the protective role of antioxidants. Exp Toxicol Pathol 2013; 65: 609-14.

  • Tripathi S, Sahu DB, Kumar R, Kumar A. Effect of acute exposure of sodium arsenite (Na3 Aso3) on some haematological parameters of Clarias batrachus (common Indian cat fish) in vivo. Indian J Environ Health 2003; 45: 183-188.

  • Dwivedi N, Flora G, Kushwaha P, Flora SJ. Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats. Environ Toxicol Pharmacol 2014; 37: 7-23.

  • Saba AB, Onakoya OM, Oyagbemi AA. Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora. J Basic Clin Physiol Pharmacol 2012; .23: 27-32.

  • Adaramoye OA, Awogbindin I, Okusaga JO. Effect of Kolaviron, a biflavonoid complex from Garcinia kola seeds, on ethanol-induced oxidative stress in liver of adult Wistar rats. J Med Food 2009; 12, 584-90.

  • Farombi EO, Shrotriya S, Surh YJ. Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci 2009; 84:149-55.

  • Adaramoye OA, Farombi EO, Nssien M, Idowu SO, Ademowo OG, Adeyemi EO. Hepatoprotective activity of purified fractions from Garcinia kola seeds in mice intoxicated with carbon tetrachloride. J Med Food 2008; 11: 544-50.

  • Emmert SW, Desai D, Amin S, Richie JP Jr. Enhanced Nrf2-dependent induction of glutathione in mouse embryonic fibroblasts by isoselenocyanate analog of sulforaphane. Bioorg Med Chem Lett 2010; 20: 2675-79.

  • Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacol Res 2008; 58: 262–70.

  • Agrawal S, Flora G, Bhatnagar P, Flora SJ. Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats. Cell Mol Biol (Noisy-le-grand) 2014; 60: 13-21.

  • Messarah, M., Klibet F, Boumendjel A, Abdennour C, Bouzerna N, Boulakoud, MS, et al. Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats. Exp Toxicol Pathol 2012; 64: 167-74.

  • Chattopadhyay S, Deb B, Maiti S. Hepatoprotective role of vitamin B12 and folic acid in arsenic intoxicated rats. Drug Chem Toxicol 2012; 35: 81-8.

  • Das AK, Bag S, Sahu R, Dua TK, Sinha MK, Gangopadhyay M, et al. Protective effect of Corchorus olitorius leaves on sodium arsenite-induced toxicity in experimental rats. Food Chem Toxicol 2010; 48: 326-35.


Abstract Views: 484

PDF Views: 0




  • Modulatory Role of Kolaviron (KV), a Biflavonoid from Garcinia kola, in Sodium Arsenite-Induced Hepatotoxicity and Haematotoxicity in Rats

Abstract Views: 484  |  PDF Views: 0

Authors

Olalekan Samson Agboola
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
Ademola Adetokunbo Oyagbemi
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
Temidayo Olutayo Omobowale
Department of Veterinary Medicine, University of Ibadan, Nigeria
Ebunoluwa Rachel Asenuga
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
Adebowale Bernard Saba
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria

Abstract


Arsenic acid (NaAsO2) is an environmental pollutant that is widely distributed in air, water and soil. Exposure to this silent killer in drinking water has posed a major health threat to both developing and developed countries of the world. The use of phytochemicals has gained acceptance in the recent years. Hence, the purpose of this study was to explore the chemopreventive effect of Kolaviron, a biflavonoid from Garcinia kola seed on NaAsO2 induced hepatoxicity and haematotoxicity. Rats were pre-treated with KV (100&amp;200mg/kg) for 7 days prior to NaAsO2 (10mg/kg; i.p.) intoxication on day 8. Complete blood counts (CBC), liver function tests, hepatic antioxidant, markers of oxidative stress and histological sections of the liver were assessed. NaAsO2 intoxication caused a significant (p<0.05) increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Also, the hepatic catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) content were significantly (p<0.05) reduced whereas markers of oxidative stress such as malondialdehyde (MDA), hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also severely (p<0.05) elevated. NaAsO2 intoxication caused a significant (p<0.05) reduction in packed cell volume (PCV), red blood cell (RBC) counts and haemoglobin (Hb) concentration. KV pre-treatment significantly suppressed markers of oxidative stress and prevented the depletion of antioxidant defence system. Normochromic normocytic anaemia precipitated by NaAsO2 intoxication was attenuated by KV administration. Histopathological examination showed that liver tissue injury mediated by arsenic was ameliorated by KV pre-treatment. It was concluded that KV may represent a potential drug candidate to protect against liver damage and other detrimental effects of arsenic toxicity.

Keywords


Hepatotoxicity, Arsenite, Kolaviron (KV), Oxidative Stress, Chemoprevention.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi1%2F146671