Abstract
Elevated serum lactate concentration has been used to predict the risk of fatality in various disease states in acutely ill patients or poisoning with different chemicals. However, its utility in predicting disease progression during acute aflatoxicosis has not been investigated. This study was designed to evaluate changes in blood lactate levels following acute exposure to aflatoxin B1 (AFB1) and to determine whether changes in blood lactate levels bear any relationship with biochemical and/or morphological lesions in the stomach, duodenum, and liver. Twenty-one male Wistar rats were randomly divided into three groups (n = 7 rats /group) including Group A (control) receiving vehicle alone and Groups B and C treated with single oral doses of AFB1 at 2.5 and 5 mg/kg, respectively. AFB1 produced significant (p < 0.05) time- and dose-dependent increase in blood lactate concentration as early as 1 h following its administration, with further increases observed at 3 h and 6 h. The hyperlactatemia accompanied tissue oxidative changes including increased H2O2 and MDA, as well as depletion in glutathione, glutathione peroxidase, superoxide dismutase, and total thiols in gastro-duodenal and hepatic tissues. The oxidative changes were reflected in morphological alterations observed at histopathology with more severe lesions observed with the higher dose of AFB1. Serum levels of pro-inflammatory cytokines (TNF-α and IL-1β) were, however, differently modified by AFB1 administration. Taken together, the results from this study gives indication that hyperlactatemia may find utility in predicting the severity of tissue damage induced by acute AFB1 exposure.
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References
Agag BI (2004) Mycotoxins in foods and feeds 1-aflatoxins. Ass Univ Bull Environ Res 7(1):173–205
Akinrinmade JF, Akinrinde AS, Amid A (2016) 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. https://doi.org/10.1007/s12550-016-0239-9
Anand R, Kumari P, Kaushal A, Bal A, Wani WY, Sunkaria A, Dua R, Singh S, Bhalla A, Gill KD (2012) Effect of acute aluminium phosphide exposure in rats: a biochemical and histological correlation. Toxicol Lett 215(1):62–69. https://doi.org/10.1016/j.toxlet.2012.09.020
Anand R, Sharma DR, Verma D, Bhalla A, Gill KD, Singh S (2013) Mitochondrial electron transport chain complexes, catalase and markers of oxidative stress in platelets of patients with severe aluminium phopsphide poisoning. Hum Exp Toxicol 32(8):807–816. https://doi.org/10.1177/0960327112468909
Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW (2013) Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 88(10):1127–1140. https://doi.org/10.1016/j.mayocp.2013.06.012
Azziz-Baumgartner E, Lindblade K, Gieseker K, Rogers HS, Kieszak S, Njapau H, Schleicher R, McCoy LF, Misore A, DeCock K, Rubin C, Slutsker L (2005) Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004. Environ Health Perspect 113(12):1779–1783. https://doi.org/10.1289/ehp.8384
Bernal W, Donaldson N, Wyncoll D, Wendon J (2002) Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet. 359:558–563
Bianco G, Russo R, Marzocco S, Velotto S, Autore G, Severino L (2012) Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites aflatoxins M1 and M2. Toxicon 59:644–650. https://doi.org/10.1016/j.toxicon.2012.02.010
Blohm E, Lai J, Neavyn M (2017) Drug-induced hyperlactatemia. Clin Toxicol 55(8):869–878. https://doi.org/10.1080/15563650.2017.1317348
Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27:951–965. https://doi.org/10.1016/s0891-5849(99)00173-2
Buetler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Ceccaroli C, Pulliero A, Geretto M, Izzotti A (2015) Molecular fingerprints of environmental carcinogens in human cancer. J Environ Sci Health 33: 188–228. https://doi.org/10.1080/10590501.2015.1030491
Dell’aglio DM, Perino LJ, Kazzi Z, Abramson J, Schwartz MD, Morgan BW (2009) Acute metformin overdose: examining serum pH, lactate level and metformin concentrations in survivors versus non-survivors: a systematic review of the literature. Ann Emerg Med 54(6):818–823. https://doi.org/10.1016/j.annemergmed.2009.04.023
Dhanasekaran D, Shanmugapriya S, Thajuddin N, Panneerselvam A (2011) Aflatoxins and aflatoxicosis in human and animals. In Aflatoxins—biochemistry and molecular. Biology:221–254. https://doi.org/10.5772/22717
Dickinson DA, Forman HJ (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol 64:1019–1026. https://doi.org/10.1016/s0006-2952(02)01172-3
Drury RA, Wallington EA, Cancerson R (1976) Carlton’s histopathological techniques, 4th edn. Oxford University Press, Oxford
Duo R, Sunkaria A, Kumar V, Gill KD (2010) Impaired mitochondrial energy metabolism and kinetic properties of cytochrome oxidase following acute aluminium phosphide exposure in rat liver. Food Chem Toxicol 48(1):53–60. https://doi.org/10.1016/j.fct.2009.09.014
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Etzel RA (2002) Mycotoxins. JAMA 287(4):425–427. https://doi.org/10.1001/jama.287.4.425
Gornal AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of Biuret reaction. J Biol Chem 177:751–766
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Hayes JD, Judah DJ, McLellan LI, Neal GE (1991) Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1. Pharmacol Ther 50:443–472. https://doi.org/10.1016/0163-7258(91)90053-o
Hinton DM, Myers MJ, Raybourne RA, Francke-Caroll S, Sotomayor RE, Shaddock J, Warbritton A, Chou MW (2003) Immunotoxicity of aflatoxin B1 in rats: effects on lymphocytes and the inflammatory response in a chronic intermittent dosing study. Toxicol Sci 73:362–377. https://doi.org/10.1093/toxsci/kfg074
Hsieh D, Wong JJ (1994) In: Eaton DL, Groopman J (eds) Pharmacokinetics and excretion of aflatoxins. The toxicology of aflatoxins: human health, veterinary and agricultural significance. Academic Press, New York
International Agency for Research on Cancer (IARC) (2002) Monograph on the evaluation of carcinogenic risk to humans, World Health Organization, some traditional herbal medicines, some mycotoxins, naphthalene and styrene. In. Summary of data reported and evaluation, Vol. 82 (pp. 171e175), Lyon
Ishikawa AT, Weese JS, Bracarense APFRL, Alfieri AA, Oliveira GG, Kawamura O, Hirooka EY, Itano EN, Costa MC (2017) Single aflatoxin B1 exposure induces changes in gut microbiota community. World Mycotoxin J 10(3):249–254
Kamala A, Shirima C, Jani B, Bakari M, Sillo H, Rusibamayila N, De Saeger S, Kimanta M, Gong YY, Simba A et al (2018) Outbreak of an acute aflatoxicosis in Tanzania during 2016. World Mycotoxin J 11(3):311–320. https://doi.org/10.3920/WMJ2017.2190
Kumar P, Mahato DK, Kamle M, Mohanta TK, Kang SG (2017) Aflatoxicosis: a global concern for food safety, human health and their management. Front Microbiol 7:2170. https://doi.org/10.3389/fmicb.2016.02170
Li Y, Ma Q-G, Zhao L-H, Wei H, Duan G-X, Zhang J-Y, Ji C (2014) Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets. Int J Mol Sci 15:5649–5662. https://doi.org/10.3390/ijms15045649
Liew W-P, Mohd-Redzwan S (2018) Mycotoxin: its impact on gut health and microbiota. Front Cell Infect Microbiol 8:60. https://doi.org/10.3389/fcimb.2018.00060
Matabaro E, Ishimwe N, Uwimbabazi E, Lee BH (2017) Current immunoassay methods for the rapid detection of aflatoxin in milk and dairy products. Compr Rev Food Sci Food Saf 16(5):808–820. https://doi.org/10.1111/1541-4337.12287
Meissonier M, Pinton P, Laffitte J, Cossalter AM, 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. https://doi.org/10.1016/j.taap.2008.04.004
Misra HP, Fridovich I (1972) The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175
Miyata M, Takano H, Guo LQ, Nagata K, Yamazoe Y (2004) Grapefruit juice intake does not enhance but rather protects against aflatoxin B 1-induced liver DNA damage through a reduction in hepatic CYP3A activity. Carcinogenesis 25(2):203–209. https://doi.org/10.1093/carcin/bgg194
Mizock BA, Falk JL (1992) Lactic acidosis in critical illness. Crit Care Med 20(1):80–93
Monson MS, Coulombe RA, Reed KM (2015) Aflatoxicosis: lessons from toxicity and responses to aflatoxin B1 in poultry. Agriculture 5:742–777. https://doi.org/10.3390/agriculture5030742
Moon EY, Pyo S (2000) Aflatoxin B (1) inhibits CD14-mediated nitric oxide production in murine peritoneal macrophages. Int J Immunopharmacol 22:237–246. https://doi.org/10.1016/S0192-0561(99)00081-8
Mwanda OW, Otieno CF, Omonge E (2005) Acute aflatoxicosis: case report. East Afr Med J 82(6):320–324. https://doi.org/10.4314/eamj.v82i6.9305
Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola O (2015) Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 30:1235–1243. https://doi.org/10.1002/tox.21994
PHS (PUBLIC HEALTH SERVICE) (1996) Public health service policy on humane care and the use of laboratory animals. US Department of Health and Humane Services, Washington, pp 99–158
Qian G, Tang L, Guo X (2014) Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats. JAppl Toxicol 34:241–249. https://doi.org/10.1002/jat.2866
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590. https://doi.org/10.1126/science.179.4073.588
Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, Weiss JW (2005) Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 45(5):524–528. https://doi.org/10.1016/j.annemergmed.2004.12.006
Sun XQ, Fu XB, Zhang R, Lu Y, Deng Q, Jiang XG, Sheng ZY (2001) Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats. World J Gastroenterol 7(4):555–558. https://doi.org/10.3748/wjg.v7.i4.555
van Hall G (2010) Lactate kinetics in human tissues at rest and during exercise. Acta Physiol (Oxford) 199(4):499–508. https://doi.org/10.1111/j.1748-1716.2010.02122.x
Varshney R, Kale RK (1990) Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. Int J Radiat Biol 58:733–743. https://doi.org/10.1080/09553009014552121
Wada K, Hashiba Y, Ohtsuka H, Kohiruimaki M, Masui M, Kawamura S, Endo H, Ogata Y (2008) Effects of mycotoxins on mitogen-stimulated proliferation of bovine peripheral blood mononuclear cells. J Vet Med Sci 70:193–196. https://doi.org/10.1292/jvms.70.193
Wei C-I, Macy JM, Hsieh DPH (1981) Biotransformation of aflatoxin B1 and its conjugated metabolites by rat gastrointestinal microfloras. Appl Environ Microbiol 41(2):549–551
Wolff SP (1994) Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol 233:182–189. https://doi.org/10.1016/S0076-6879(94)33021-2
Yao YM, Yu Y, Wu Y, Lu L-R, Sheng Z-Y (1997) Plasma D (-)-lactate as a new marker for diagnosis of acute intestinal injury following ischemia-reperfusion. World J Gastroenterol 3(4):225–227. https://doi.org/10.3748/wjg.v3.i4.225
Yao H, Hruska Z, Di Mavungu JD (2015) Developments in detection and determination of aflatoxins. World Mycotoxin J 8(2):181–191. https://doi.org/10.3920/WMJ2014.1797
Yılmaz S, Kaya E, Comakli S (2017) Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats. Adv Clin Exp Med 26(6):907–917. https://doi.org/10.17219/acem/66347
Zhang J, Zheng N, Liu J, Li FD, Li SL, Wang JQ (2015) Aflatoxin B1 and aflatoxin M1 induced cytotoxicity and DNA damage in differentiated and undifferentiated Cac0-2 cells. Food Chem Toxicol 83:54–60. https://doi.org/10.1016/j.fct.2015.05.020
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Akinrinde, A.S., Ogunbunmi, T. & Akinrinmade, F.J. Acute aflatoxin B1-induced gastro-duodenal and hepatic oxidative damage is preceded by time-dependent hyperlactatemia in rats. Mycotoxin Res 36, 443–452 (2020). https://doi.org/10.1007/s12550-020-00408-6
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DOI: https://doi.org/10.1007/s12550-020-00408-6