Abstract
Aflatoxins are known to produce chronic carcinogenic, mutagenic, and teratogenic effects, as well as acute inflammatory effects, especially in the gastrointestinal tract. The potentials of the flavonoid-rich extract from Chromolena odorata (FCO) and melatonin (a standard anti-oxidant and anti-inflammatory agent) against aflatoxin B1 (AFB1)-induced alterations in pro-inflammatory cytokine levels and morphology of liver and small intestines were evaluated in this study. We utilized Wistar albino rats (200–230 g) randomly divided into five groups made up of group A, control rats; group B, rats given AFB1 (2.5 mg/kg, intraperitoneal) twice on days 5 and 7; rats in groups C, D, and E were treated with melatonin (10 mg/kg, intraperitoneal) or oral doses of FCO1 (50 mg/kg) and FCO2 (100 mg/kg) for 7 days, respectively, along with AFB1 injection on days 5 and 7. Serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were determined using commercial ELISA kits and histopathological evaluation of the liver, duodenum, and ileum were also carried out. We observed significant elevation (p < 0.05) in serum IL-1β correlating with hemorrhages and leucocytic and lymphocytic infiltration in the liver and intestines as evidences of an acute inflammatory response to AFB1 administration. All treatments yielded significant reduction (p < 0.05) in IL-1β levels, although TNF-α levels were not significantly altered in all rats that received AFB1, irrespective of the treatments. Melatonin and FCO2 produced considerable protection of hepatic tissues, although melatonin was not quite effective in protecting the intestinal lesions. Our findings suggest a modulation of cytokine expression that may, in part, be responsible for the abilities of C. odorata or melatonin in amelioration of hepatic and intestinal lesions associated with aflatoxin B1 injury.
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References
Abdulmajeed NA (2011) Therapeutic ability of some plant extracts on aflatoxin-B1 induced renal and cardiac damage. Arabian J Chem 4:1–10
Akinrinmade JF, Akinrinde AS, Odejobi A, Oyagbemi AA (2015) Evidence of attenuation of intestinal ischemia-reperfusion injury following pre-treatment with methanolic extracts of Chromolena odorata in rats. J Complem Integr Med 12(1):23–32
Babior BM (2000) Phagocytes and oxidative stress. Am J Med 109:33–44
Baker DC, Green RA (1987) Coagulation defects of aflatoxins in toxicated rabbits. Vet Pathol 24:62–70
Bedard LL, Massey TE (2006) Aflatoxin B1-induced damage and its repair. Cancer Lett 241:174–183
Botta N, van de Venter M, Downing TG, Shephard EG, Gehringer MM (2004) The effect of intraperitoneally administered microcystin-LR on the gastrointestinal tract of BALB/c mice. Toxin 43:251–254
Bruneau J, Loscher C, O’Kennedy R (2009) Investigation of the immune-modulatory effects of aflatoxin B1, B2 and G1. Epidemiology 20(6):S42–S43
Bubenik GA (2002) Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47:2336–2348
Carrillo-Vico A, Lardone PJ, Naji L, Fernández-Santos JM, Martín-Lacave I, Guerrero JM, Calvo JR (2005) Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in mice: regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res 39:400–408
Cometa MF, Lorenzini P, Fortuna S, Volpe MT, Menequz A, Palmery M (2005) In vitro inhibitory effect of aflatoxin B1 on acetylcholinesterase activity in mouse brain. Toxicology 206(1):125–135
Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM (2000) Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res 28:193–202
Dafalla R, Yagi A, Adam S (1987) Experimental aflatoxicosis in hybro-type chicks: sequential changes in growth and serum constituents and histopathological changes. Vet Hum Toxicol 29:222–225
Eaton D, Ramsdell H, Neal G (1994) Biotransformation of aflatoxins. In: Eaton L, Groopman J (eds) The toxicology of aflatoxins, human health, veterinary agricultural significance. Academic Press, New York, NY
Erben U, Loddenkemper C, Doerfel K, Speickermann S, Haller D, Heimesaat MM, Zeitz M, Siegmund B, Kuhl AA (2014) A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Cli Exp Pathol 7(8):4557–4576
Grenier B, Applegate TJ (2013) Invited review—modulation of intestinal functions upon mycotoxin ingestion: meta-analysis of published experiments in animals. Toxins 5:396–430
Grenier B, Bracarense AP, Schwartz HE, Trumel C, Cossalter AM, Schatzmayr G, Kolf-Clauw M, Moll WD, Oswald IP (2012) The low intestinal and hepatic toxicity of hydrolyzed fumonisin B 1 correlates with its inability to alter the metabolism of sphingolipids. Biochem Pharmacol 83:1465–1473
Gross-Steinmeyer K, Eaton DL (2012) Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1. Toxicology 299:69–79
Gupta RC (2011) Aflatoxins, ochratoxins and citrinin. In: Gupta RC (ed) Reproductive and developmental toxicology. Academic Press, San Diego, CA
Hanh TTH, Hang DTT, Minh CV, Dat NT (2011). Anti-inflammatory effects of fatty acids isolated from Chromolena odorata. Asian Pacific J Trop Med 760–763.
Hsieh D, Wong JJ (1994) Pharmacokinetics and excretion of aflatoxins. In: Eaton DL, Groopman J (eds) The toxicology of aflatoxins: human health, veterinary and agricultural significance. Academic Press, New York, NY
Ito E, Kondo F, Harada K (2001) Intratracheal administration of microcystin-LR and its distribution. Toxicon 39:265–271
Joseph GS, Jayaprakasha GK, Selvi AT, Jena BS, Sakariah KK (2005) Antiaflatoxigenic and antioxidant activities of Garcinia extracts. Int J Food Microbiol 101:153–160
Jung KH, Hong SW, Zheng HM, Lee DH, Hong SS (2009) Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappa B during prevention of oxidative liver injury in a dimethylnitrosamine model. J Pineal Res 47:173–183
Kanaoka Y, Boyce JA (2004) Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J. Immunol. 173:1503–1510
Kanashiro A, Kabeya LM, Polizello ACM, Lopes NP, Lopes JLC, Lucisano-Valim YM (2004) Inhibitory activity of flavonoids from Lychnophora sp. on generation of reactive oxygen species by neutrophils upon stimulation by immune complexes. Phytother Res 18:61–65
Kerns W, Swhartz L, Blanchard K, Burchiel S, Essayan D, Fung E, Johnson R, Lawton M, Louden C, MacGregor T et al (2005) Drug-induced vascular injury—a quest for biomarkers. Toxicol Appl Pharmacol 203:62–87, 2005
Kumagai S, Sugita-Konishi Y, Hara-Kudo Y, Ito Y, Noguchi Y, Yamamoto Y, Ogura A (1998) The fate and acute toxicity of aflatoxin B1 in the mastomys and rat. Toxicon 36(1):179–188
Kumar R, Mishra AK, Dubey NK, Tripathi YB (2007) Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal, antiaflatoxigenic and antioxidant activity. Int J Food Microbiol 115:159
Lacour S, Gautier JC, Pallardy M, Roberts R (2005) Cytokines as potential biomarkers of liver toxicity. Cancer Biomark 1:29–39
Li Y, Ma QG, Zhao LH, Wei H, Duan GX, Zhang JY, Ji C (2014) Effects of lipoic acid on immune function, the antioxidant defense system and inflammation-related gene expression of broiler chickens fed aflatoxin-contaminated diets. Int J Mol Sci 15(4):5469–62
Ling SK, Mazura MD, Salbiah M (2007) Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson. Biol Pharm Bull 30:1150–1152
Mathes AM (2010) Hepatoprotective actions of melatonin: possible mediation by melatonin receptors. World J Gastroenterol 16(48):6087–6097
Meisonnier GM, Pinton P, Laffitte J, Cossalter A, Gong YY, Wild CP, Bertin G, Galtier P, Oswald IP (2008) Immunotoxicity of aflatoxin B1: impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression. Toxicol Appl Pharmacol 231:142–149
Moon E, Rhee D, Pyo S (1999a) In vitro suppressive effect of aflatoxin B1 on murine peritoneal macrophage functions. Toxicology 133:171–179
Moon E, Rhee D, Pyo S (1999b) Inhibition of various functions in murine peritoneal macrophages by aflatoxin B1 exposure in vivo. Int J Immunopharmacology 21:47–58
Nur Jannah MH, Mahmood AA, Sidik K, Salmah I (2006) Cytoprotective effects of honey in combination with aqueous and ethanol extracts from Chromolaena odorata L (Eupatorium odoratum) in rats. JUMMEC 9:7–13
Omokhua AG, et al. (2015) Chromolaena odorata (L.) R.M. King & H. Rob. (Asteraceae) in sub-Saharan Africa: A synthesis and review of its medicinal potential. J Ethnopharmacol http://dx.doi.org/10.1016/j.jep.2015.04.057i.
Owoyele VB, Adediji JO, Soladoye AO (2005) Anti-inflammatory activity of aqueous leaf extract of Chromolaena odorata. Inflammopharmacology 13(5–6):479–484
Palipoch S, Punsawad C, Chinnapun D, Suwannalert P (2013) Histopathology of the small intestine induced by cisplastin in male Wistar rats. Walailak J Sci Tech 10(6):657–663
Peraica M, Radic B, Lucic A, Pavlovic M (1999) Toxic effects of mycotoxins in humans. Bull World Health Organ 77:754–766
Phan TT, Wang L, See P, Grayer RJ, Chan SY, Lee ST (2001) Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing. Biol Pharm Bull 24:1373–1379
Qian G, Tang L, Guo X, Wang F, Massey ME, Su J, Guo TL, Williams JH, Phillips TD, Wang JS (2014) Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats. J Appl Toxicol 34(3):241–249
Ravinayagam V, Jaganathan R, Panchanadham S, Palanivelu S (2012) Potential antioxidant role of tridham in managing oxidative stress against aflatoxin B1-induced experimental hepatocellular carcinoma. Int J Hepatol. doi:10.1155/2012/428373
Rossano F, Ortega D, Buommino E, Cusumano V, Losi E, Catania MR (1999) Secondary metabolites of Aspergillus exert immunobiological effects on human monocytes. Res Microbiol 150:13–19
Rostasy KM (2005) Inflammation and neuroaxonal injury in multiple sclerosis and AIDS dementia complex: Implications for neuroprotective treatment. Neuropediatrics 36:230–239
Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ (1995) Contribution of interleukin 1beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Bri J Pharmacol 115:1265–1275
Salim AB, Zohair A, Hegazy AES et al (2011) Effect of some strains of probiotic bacteria against toxicity induced by aflatoxicosis in vivo. J Am Sci 7(1):1–12
Sergent T, Ribonnet L, Kolosova A, Garsou S, Schant A, De Saege S, Van Peteghem C, Larondelle Y, Pussemier L, Schneider YJ (2008) Molecular and cellular effects of food contaminants and secondary plant components and their plausible interactions at the intestinal level. Food Chem Toxicol 46:813–841
Shibamoto T, Bjeldanes LF (2009) Introduction to Food toxicology. Academic Press.
Singh KB, Maurya BK, Trigun SK (2015) Activation of oxidative stress and inflammatory factors could account for histopathological progression of aflatoxin B1 induced hepatocarcinogenesis in rat. Mol Cell Biochem 401(1–2):185–196
Spelman K, Burns JJ, Nichols D, Winters N, Ottersberg S, Tenborg M (2006) Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Alt Med Rev 11(2):128–150
Takai N, Kataoka M, Higochi Y, Matsuura K, Yamamoto S (1997) Primary structure of rat CD14 and characteristics of rat CD14, cytokine and NO synthase mRNA expression in mononuclear phagocyte system cells in response to LPS. J Leukocyte Biol 61:736–744
Taleb-Contini SH, Kanashiro A, Kabeya LM, Polizello ACM, Lucisano-Valim YM, Oliveira DCR (2006) Immunomodulatory effects of methoxylated flavonoids from two Chromolena species: structure activity relationships. Phytother Res 20:573–575
Tarrant JM (2010) Blood cytokines as biomarkers of in vivo toxicity in pre-clinical safety assessment: considerations for their use. Toxicol Sci 117(1):4–16
Tijmes M, Pedraza R, Valladares L (1996) Melatonin in the rat testis: evidence for local synthesis. Steroids 61:65–68
Wang H, Wei W, Wang NP, Gui SY, Wu L, Sun WY, Xu XY (2005) Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress. Life Sci 77:1902–1915
Wu CC, Chiao CW, Hsiao G, Chen A, Yen MH (2001) Melatonin prevents endotoxin-induced circulatory failure in rats. J Pineal Res 30:147–156
Zhu H, Wang Y, Liu Y, Xia Y, Tang T (2010) Analysis of flavonoids in Portulaca oleracea L. by UV–vis spectrophotometry with comparative study on different extraction technologies. Food Anal Methods 3(2):90–97
Acknowledgments
The authors are grateful to Dr. Joseph Atehnkeng of the Aflasafe Laboratory at the International Institute of Tropical Agriculture, Ibadan, Nigeria for provision of aflatoxin B1 used in this study.
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Akinrinmade, F.J., Akinrinde, A.S. & Amid, A. Changes in serum cytokine levels, hepatic and intestinal morphology in aflatoxin B1-induced injury: modulatory roles of melatonin and flavonoid-rich fractions from Chromolena odorata . Mycotoxin Res 32, 53–60 (2016). https://doi.org/10.1007/s12550-016-0239-9
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DOI: https://doi.org/10.1007/s12550-016-0239-9