Abstract
Arsenic and chromium are the most common environmental toxicants prevailing in nature. Hence, the present study endeavors to investigate the salutary effects of Coenzyme Q10 (CoQ10), Biochanin A (BCA), and Phloretin (PHL) on the combined neurotoxic impact of arsenic and chromium in the Swiss albino mice (Mus musculus). Sodium meta-arsenite (100 ppm) and potassium dichromate (75 ppm) were given orally in conjugation with CoQ10 (10 mg/kg), BCA & PHL (50 mg/kg each) in accordance with body weight per day for the 2 weeks experimental duration. Weight reduction was figured out in the exposed toxic group of arsenic and chromium in contrast with the comparison group (control), and with the selected anti-oxidants treatment, it rose significantly to the basal status (p < 0.05). The concentration of arsenic and chromium was reduced significantly (p < 0.001) amidst all the natural compounds co-medicated groups. Anti-oxidant indicators, viz. lipid peroxidation (LPO) and protein carbonyl content (PCC), were found elevated, with reduction observed in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione s-transferase (GST), and total thiols (TT) in the arsenic and chromium, co-exposed mice. The alterations in redox homeostasis were well corroborated with the estimations of cholinesterase’s enzymes (p < 0.05) along with DNA fragmentation assay and altered Nrf2 signaling. The administration of CoQ10, BCA, and PHL ameliorated the effects of arsenic and chromium induced oxidative stress in the exposed mice. Our research unfolds the remedial outcome of these natural compounds contrary to the combined arsenic and chromium associated-neurotoxicity in the experimental model.
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References
Abiko Y, Shinkai Y, Sumi D, Kumagai Y (2010) Reduction of arsenic-induced cytotoxicity through Nrf2/HO-1 signaling in HepG2 cells. J Toxicol Sci 35:419–423. https://doi.org/10.2131/jts.35.419
Acharyya N, Chattopadhyay S, Maiti S (2014) Chemoprevention against arsenic-induced mutagenic DNA breakage and apoptotic liver damage in rat via antioxidant and SOD1 upregulation by green tea (Camellia sinensis) which recovers broken DNA resulted from arsenic-H2O2 related in vitro oxidant stress. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 32:338–361. https://doi.org/10.1080/10590501.2014.967061
Agnihotri SK, Agrawal U, Ghosh I (2015) Brain most susceptible to cadmium induced oxidative stress in mice. J Trace Elem Med Biol 30:184–193. https://doi.org/10.1016/j.jtemb.2014.12.008
Ahmad S, Kitchin KT, Cullen WR (2000) Arsenic species that cause release of iron from ferritin and generation of activated oxygen. Arch Biochem Biophys 382:195–202. https://doi.org/10.1006/abbi.2000.2023
Alizadeh-Ghodsi M, Zavvari A, Ebrahimi-Kalan A, Shiri-Shahsavar MR, Yousefi B (2018) The hypothetical roles of arsenic in multiple sclerosis by induction of inflammation and aggregation of tau protein: a commentary. Nutr Neurosci 21:92–96. https://doi.org/10.1080/1028415X.2016.1239399
Arif M, Fareed S, Rahman MA (2016) Stress relaxant and antioxidant activities of acid glycoside from Spondias mangifera fruit against physically and chemically challenged albino mice. J Pharm Bioallied Sci 8:58–63. https://doi.org/10.4103/0975-7406.171685
Bhattacharya S (2017) Medicinal plants and natural products in amelioration of arsenic toxicity: a short review. Pharm Biol 55:349–354. https://doi.org/10.1080/13880209.2016.1235207
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. https://doi.org/10.1016/s0076-6879(78)52032-6
Cassady JM, Zennie TM, Chae YH, Ferin MA, Portuondo NE, Baird WM (1988) Use of a mammalian cell culture benzo(a)pyrene metabolism assay for the detection of potential anticarcinogens from natural products: inhibition of metabolism by biochanin A, an isoflavone from Trifolium pratense L. Cancer Res 48:6257–6261
Castro-Coronel Y, Del Razo LM, Huerta M, Hernandez-Lopez A, Ortega A, Lopez-Bayghen E (2011) Arsenite exposure downregulates EAAT1/GLAST transporter expression in glial cells. Toxicol Sci 122:539–550. https://doi.org/10.1093/toxsci/kfr126
Dashti A, Soodi M, Amani N (2016) Cr (VI) induced oxidative stress and toxicity in cultured cerebellar granule neurons at different stages of development and protective effect of Rosmarinic acid. Environ Toxicol 31:269–277. https://doi.org/10.1002/tox.22041
Diaz-Mayans J, Laborda R, Nunez A (1986) Hexavalent chromium effects on motor activity and some metabolic aspects of Wistar albino rats. Comp Biochem Physiol C Comp Pharmacol Toxicol 83:191–195. https://doi.org/10.1016/0742-8413(86)90035-6
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Fatima R, Akhtar K, Hossain MM, Ahmad R (2017) Chromium oxide nanoparticle-induced biochemical and histopathological alterations in the kidneys and brain of Wistar rats. Toxicol Ind Health 33:911–921. https://doi.org/10.1177/0748233717735266
Ferri P, Angelino D, Gennari L, Benedetti S, Ambrogini P, Del Grande P, Ninfali P (2015) Enhancement of flavonoid ability to cross the blood–brain barrier of rats by co-administration with alpha-tocopherol. Food Funct 6:394–400. https://doi.org/10.1039/c4fo00817k
Figueira I et al (2017) Polyphenols journey through blood-brain barrier towards neuronal protection. Sci Rep 7:11456. https://doi.org/10.1038/s41598-017-11512-6
Firdaus F, Zafeer MF, Ahmad M, Afzal M (2018) Anxiolytic and Anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats. Heliyon 4:e00650. https://doi.org/10.1016/j.heliyon.2018.e00650
Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281. https://doi.org/10.1016/j.freeradbiomed.2011.04.008
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Han XD, Zhang YY, Wang KL, Huang YP, Yang ZB, Liu Z (2017) The involvement of Nrf2 in the protective effects of (−)-Epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity. Oncotarget 8:65302–65312. https://doi.org/10.18632/oncotarget.18582
Hawkins RD, Son H, Arancio O (1998) Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Prog Brain Res 118:155–172. https://doi.org/10.1016/s0079-6123(08)63206-9
Herrera A, Pineda J, Antonio MT (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. https://doi.org/10.1016/j.etap.2013.03.018
Hu ML (1994) Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 233:380–385. https://doi.org/10.1016/s0076-6879(94)33044-1
Jalaludeen AM, Lee WY, Kim JH, Jeong HY, Ki KS, Kwon EG, Song H (2015) Therapeutic efficacy of biochanin A against arsenic-induced renal and cardiac damage in rats. Environ Toxicol Pharmacol 39:1221–1231. https://doi.org/10.1016/j.etap.2015.04.020
Kamal M, Naz M, Jawaid T, Arif M (2019) Natural products and their active principles used in the treatment of neurodegenerative diseases: a review. Orient Pharm Exp Med 19:343–365. https://doi.org/10.1007/s13596-019-00396-8
Kozul-Horvath CD, Zandbergen F, Jackson BP, Enelow RI, Hamilton JW (2012) Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development. PLoS ONE 7:e38249. https://doi.org/10.1371/journal.pone.0038249
Levine RL, Berlett BS, Moskovitz J, Mosoni L, Stadtman ER (1999) Methionine residues may protect proteins from critical oxidative damage. Mech Ageing Dev 107:323–332. https://doi.org/10.1016/s0047-6374(98)00152-3
Lipton SA et al (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632. https://doi.org/10.1038/364626a0
Mahmoud AM, Abd El-Twab SM (2017) Caffeic acid phenethyl ester protects the brain against hexavalent chromium toxicity by enhancing endogenous antioxidants and modulating the JAK/STAT signaling pathway. Biomed Pharmacother 91:303–311. https://doi.org/10.1016/j.biopha.2017.04.073
Mahringer A et al (2010) Inhibition of P-glycoprotein at the blood-brain barrier by phytochemicals derived from traditional Chinese medicine. Cancer Genom Proteom 7:191–205
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA 95:8892–8897. https://doi.org/10.1073/pnas.95.15.8892
Muthumani M, Miltonprabu S (2015) Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats. Chem Biol Interact 235:95–105. https://doi.org/10.1016/j.cbi.2015.04.006
Nagaraja TN, Desiraju T (1994) Effects on operant learning and brain acetylcholine esterase activity in rats following chronic inorganic arsenic intake. Hum Exp Toxicol 13:353–356. https://doi.org/10.1177/096032719401300511
Pace C, Dagda R, Angermann J (2017) Antioxidants protect against arsenic induced mitochondrial cardio-toxicity. Toxics. https://doi.org/10.3390/toxics5040038
Patlolla AK, Barnes C, Yedjou C, Velma VR, Tchounwou PB (2009) Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague–Dawley rats. Environ Toxicol 24:66–73. https://doi.org/10.1002/tox.20395
Prakash C, Soni M, Kumar V (2015) Biochemical and molecular alterations following arsenic-induced oxidative stress and mitochondrial dysfunction in rat brain. Biol Trace Elem Res 167:121–129. https://doi.org/10.1007/s12011-015-0284-9
Pratush A, Kumar A, Hu Z (2018) Adverse effect of heavy metals (As, Pb, Hg, and Cr) on health and their bioremediation strategies: a review. Int Microbiol 21:97–106. https://doi.org/10.1007/s10123-018-0012-3
Ratnaike RN (2003) Acute and chronic arsenic toxicity. Postgrad Med J 79:391–396. https://doi.org/10.1136/pmj.79.933.391
Rezk BM, Haenen GR, van der Vijgh WJ, Bast A (2002) The antioxidant activity of phloretin: the disclosure of a new antioxidant pharmacophore in flavonoids. Biochem Biophys Res Commun 295:9–13. https://doi.org/10.1016/s0006-291x(02)00618-6
Rice-Evans C (2001) Flavonoid antioxidants. Curr Med Chem 8:797–807. https://doi.org/10.2174/0929867013373011
Rodriguez VM, Carrizales L, Jimenez-Capdeville ME, Dufour L, Giordano M (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55:301–308. https://doi.org/10.1016/s0361-9230(01)00477-4
Salama A, Hegazy R, Hassan A (2016) Intranasal chromium induces acute brain and lung injuries in rats: assessment of different potential hazardous effects of environmental and occupational exposure to chromium and introduction of a novel pharmacological and toxicological animal model. PLoS ONE 11:e0168688. https://doi.org/10.1371/journal.pone.0168688
Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360:201–205. https://doi.org/10.1124/jpet.116.237503
Schaumloffel N, Gebel T (1998) Heterogeneity of the DNA damage provoked by antimony and arsenic. Mutagenesis 13:281–286. https://doi.org/10.1093/mutage/13.3.281
Scott N, Hatlelid KM, MacKenzie NE, Carter DE (1993) Reactions of arsenic (III) and arsenic (V) species with glutathione. Chem Res Toxicol 6:102–106. https://doi.org/10.1021/tx00031a016
Sharma A, Kshetrimayum C, Sadhu HG, Kumar S (2018) Arsenic-induced oxidative stress, cholinesterase activity in the brain of Swiss albino mice, and its amelioration by antioxidants vitamin E and coenzyme Q10. Environ Sci Pollut Res Int 25:23946–23953. https://doi.org/10.1007/s11356-018-2398-z
Sinczuk-Walczak H (2009) Nervous system disorders induced by occupational exposure to arsenic and its inorganic compounds: a literature review. Med Pracy 60:519–522
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191. https://doi.org/10.1016/0014-4827(88)90265-0
Singh G, Thaker R, Sharma A, Parmar D (2021) Therapeutic effects of biochanin A, phloretin, and epigallocatechin-3-gallate in reducing oxidative stress in arsenic-intoxicated mice. Environ Sci Pollut Res Int 28:20517–20536. https://doi.org/10.1007/s11356-020-11740-w
Sirvio J, Soininen HS, Kutvonen R, Hyttinen JM, Helkala EL, Riekkinen PJ (1987) Acetyl- and butyrylcholinesterase activity in the cerebrospinal fluid of patients with Parkinson’s disease. J Neurol Sci 81:273–279. https://doi.org/10.1016/0022-510x(87)90102-x
Snyder SH (1993) Janus faces of nitric oxide. Nature 364:577. https://doi.org/10.1038/364577a0
Soudani N, Troudi A, Amara IB, Bouaziz H, Boudawara T, Zeghal N (2012) Ameliorating effect of selenium on chromium (VI)-induced oxidative damage in the brain of adult rats. J Physiol Biochem 68:397–409. https://doi.org/10.1007/s13105-012-0152-4
Sugiyama M (1992) Role of physiological antioxidants in chromium (VI)-induced cellular injury. Free Radic Biol Med 12:397–407. https://doi.org/10.1016/0891-5849(92)90089-y
Suzuki YJ, Carini M, Butterfield DA (2010) Protein carbonylation. Antioxid Redox Signal 12:323–325. https://doi.org/10.1089/ars.2009.2887
Wang J et al (2015) Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage and oxidative stress in a rat model of Parkinson’s disease. Pharmacol Biochem Behav 138:96–103. https://doi.org/10.1016/j.pbb.2015.09.013
Wang G, Fowler BA (2008) Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic. Toxicol Appl Pharmacol 233:92–99. https://doi.org/10.1016/j.taap.2008.01.017
WHO (2018) https://www.who.int/news-room/fact-sheets/detail/arsenic. Accessed 20 Nov 2021
Xi S, Guo L, Qi R, Sun W, Jin Y, Sun G (2010) Prenatal and early life arsenic exposure induced oxidative damage and altered activities and mRNA expressions of neurotransmitter metabolic enzymes in offspring rat brain. J Biochem Mol Toxicol 24:368–378. https://doi.org/10.1002/jbt.20349
Yen CC et al (2011) Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway. Arch Toxicol 85:565–575. https://doi.org/10.1007/s00204-011-0709-y
Zhu X, Perry G, Moreira PI, Aliev G, Cash AD, Hirai K, Smith MA (2006) Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease. J Alzheimers Dis 9:147–153. https://doi.org/10.3233/jad-2006-9207
Acknowledgements
The authors are thankful to the Director, ICMR-NIOH Ahmedabad, for conducting this study. The authors also acknowledge the assistance from Animal House Facility staff, especially Dr. Rajendra Palkhade, during the study. The authors are also grateful to the Zydus Research Center (ZRC), Ahmedabad, for providing the male Swiss albino mice for the study.
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ST: investigation, visualization, writing—original draft preparation. SF: investigation, visualization, DP: investigation, visualization, DPS and SM: resources, RM: investigation, resources, GS: conceptualization, visualization, supervision, writing—reviewing and editing.
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All the animal experimental procedures of the present study were conducted in accordance with the Institutional Animal Ethics Committee (IAEC) of the ICMR-National Institute of Occupational Health (NIOH), Ahmedabad wide approval no. IAEC/NIOH/2018–19/21/02/M.
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Tripathi, S., Fhatima, S., Parmar, D. et al. Therapeutic effects of CoenzymeQ10, Biochanin A and Phloretin against arsenic and chromium induced oxidative stress in mouse (Mus musculus) brain. 3 Biotech 12, 116 (2022). https://doi.org/10.1007/s13205-022-03171-w
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DOI: https://doi.org/10.1007/s13205-022-03171-w