Top

Published in:

01-01-2020 | Interferon | Original Article

The therapeutic and protective effects of bee pollen against prenatal methylmercury induced neurotoxicity in rat pups

Authors: Abir Ben Bacha, Al-Orf Norah, May Al-Osaimi, Abdel Halim Harrath, Lamjed Mansour, Afaf El-Ansary

Published in: Metabolic Brain Disease | Issue 1/2020

Abstract

The current study evaluated the protective and therapeutic potency of bee pollen in ameliorating the toxic effects of methylmercury (MeHg), by measuring certain biochemical parameters related to neurotransmission, neuroinflammation, apoptosis, and glutamate excitotoxicity in the male neonate brain. Healthy, pregnant female rats (N = 40) were randomly divided into 5 groups, each comprising10 male neonates, as follows: (i) neonates delivered by control mothers; (ii) neonates delivered by MeHg-treated mothers who received 0.5 mg/kg BW/day MeHg via drinking water from gestational day 7 till postnatal day 7; (iii) neonates delivered by bee pollen treated mothers who received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks; (iv) protective group of neonates delivered by MeHg and bee pollen-treated mothers, who continued to receive bee pollen until day 21 at the same dose, and (v) therapeutic group of neonates delivered by MeHg- treated mothers followed by bee pollen treatment, wherein they received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks. Selected biochemical parameters in brain homogenates from each group were measured. MeHg-treated groups exhibited various signs of brain toxicity, such as a marked reduction in neurotransmitters (serotonin (5-HT), nor-adrenalin (NA), dopamine (DA)) and gamma aminobutyric acid (GABA) and elevated levels of interferon gamma (IFN-γ), caspase-3, and glutamate (Glu). Bee pollen effectively reduced the neurotoxic effects of MeHg. Minimal changes in all measured parameters were observed in MeHg-treated animals compared to the control group. Therefore, bee pollen may safely improve neurotransmitter defects, inflammation, apoptosis, and glutamate excitotoxicity.

Agilan B, Rajendra Prasad N, Kanimozhi G, Karthikeyan R, Ganesan M, Mohana S, Velmurugan D, Ananthakrishnan D. Caffeic acid inhibits chronic UVB-induced cellular proliferation through JAK-STAT3 signaling in mouse skin. Photochem Photobiol 2016 May;92(3):467–474. doi: https://doi.org/10.1111/php.12588. Epub 2016 Apr 21.PubMedPubMed

Aldgini HMM, Al-Abbadi AA, Abu-Nameh ESM, Alghazeer Rabia O (2019) Determination of metals as bio indicators in some selected bee pollen samples from Jordan. Saudi Journal of Biological Sciences In press

Allen JW, Mutkus LA, Aschner M (2001a) Methylmercury-mediated inhibition of 3H-D-aspartate transport in cultured astrocytes is reversed by the antioxidant catalase. Brain Res 902:92–100PubMed

Allen JW, Shanker G, Aschner M (2001b) Methylmercury inhibits the in vitro uptake of the glutathione precursor, cystine, in astrocytes, but not in neurons. Brain Res 894:131–140PubMed

Al-Salem HS, Bhat RS, Al-Ayadhi L, El-Ansary A (2016) Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid. BMC Complement Altern Med 16:120–130PubMedPubMedCentral

Antunes Dos Santos A, Appel Hort M, Culbreth M, Lopez-Granero C, Farina M, Rocha JB, Aschner M (2016) Methylmercury and brain development: a review of recent literature. J Trace Elem Med Biol 38:99–107PubMed

Arnold GL, Hyman SL, Mooneyra K (2003) Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord 33:449–454PubMed

Aschner M, Clarkson TW (1988) Uptake of methylmercury in the rat brain: effects of amino acids. Brain Res 462:31–39PubMed

Aschnerm DYL, Gannon M, Kimelberg HK (1993) Methylmercury-induced alterations in excitatory amino acid transport in rat primary astrocyte cultures. Brain Res 602:181–186

Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221:614–620PubMed

Brookes N (1992) In vitro evidence for the role of glutamate in the CNS toxicity of mercury. Toxicology 76:245–256PubMed

Charleston JS, Bolender RP, Mottet NK, Body RL, Vahter ME, Burbacher TM (1994) Increases in the number of reactive glia in the visual cortex of Macaca fascicularis following subclinical long-term methyl mercury exposure. Toxicol Appl Pharmacol 129:196–206PubMed

Clifton JC (2007) Mercury exposure and public health. Pediatr Clin N Am 54:e1–237-e1-245

De Andrade Teles RB, Diniz TC, Costa Pinto TC, De Oliveira Júnior RG, Gama E Silva M, De Lavor ÉM, Fernandes AWC, De Oliveira AP, De Almeida Ribeiro FPR, Da Silva AAM, Cavalcante TCF, Quintans Júnior LJ, Da Silva Almeida JRG (2018) Flavonoids as therapeutic agents in Alzheimer's and Parkinson's diseases: a systematic review of preclinical evidences. Oxidative Med Cell Longev 7043213:1–21

Debes F, Budtz-Jørgensen E, Weihe P, White RF, Grandjean P (2006) Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol 28:363–375PubMedPubMedCentral

Degrandi-Hoffman G, Eckholm BJ, Huang MH (2013) A comparison of bee bread made by Africanized and European honey bees (Apis mellifera) and its effects on hemolymph protein titers. Apidologie 44:52–63

Duarte J, Francisco V, Perez-Vizcaino F (2014) Modulation of nitric oxide by flavonoids. Food Funct 5:1653–1668PubMed

El Asar HM, Mohammed EA, Aboulhoda BE, Emam HY, Imam AA (2019) Selenium protection against mercury neurotoxicity: modulation of apoptosis and autophagy in the anterior pituitary. Life Sci 15(231):116578

El-Ansary S, Shaker GH, Rizk MZ (2013) Role of gut-brain Axis in the Aetiology of neurodevelopmental disorders with reference to autism. Journal of Clinical Toxicology S6:005–013

El-Ansary A, Al-Salem HS, Asma A, Al-Dbass A (2017a) Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen. Lipids Health Dis 16:96–96PubMedPubMedCentral

El-Ansary A, Al-Salem HS, Asma A, Al-Dbass A (2017b) Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen. Lipids Health Dis 16:96–105PubMedPubMedCentral

Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516PubMedPubMedCentral

Eraslan G, Kanbur M, Silici S, Cem Liman B, Altinordulu S, Soyer Sarica Z (2009) Evaluation of protective effect of bee pollen against propoxur toxicity in rat. Ecotoxicol Environ Saf 72:931–937PubMed

Erkmen O, Özcan MM (2008) Antimicrobial effects of Turkish Propolis, pollen, and Laurel on spoilage and pathogenic food-related microorganisms. J Med Food 11:587–592PubMed

Foerster BR, Pomper MG, Callaghan BC, Petrou M, Edden RAE, Mohamed MA, Welsh RC, Carlos RC, Barker PB, Feldman EL (2013) An imbalance between excitatory and inhibitory neurotransmitters in amyotrophic lateral sclerosis revealed by use of 3-T proton magnetic resonance spectroscopy. JAMA neurology 70:1009–1016PubMedPubMedCentral

Franco JL, Posser T, Missau F, Pizzolatti MG, Dos Santos ARS, Souza DO, Aschner M, Rocha JBT, Dafre AL, Farina M (2010) Structure-activity relationship of flavonoids derived from medicinal plants in preventing methylmercury-induced mitochondrial dysfunction. Environ Toxicol Pharmacol 30:272–278PubMedPubMedCentral

Guom SY, Gao Q, Du H, Zeng W, Wangy HX, Jiang X (2015) The protective mechanism of Ginkgolides and Ginkgo flavonoids on the TNF-α induced apoptosis of rat hippocampal neurons and its mechanisms in vitro. Heliyon 1:e00020–e00020

Gustin K, Tofail F, Mehrin F, Levi M, Vahter M, Kippler M (2017) Methylmercury exposure and cognitive abilities and behavior at 10years of age. Environ Int 102:97–105PubMed

Hashioka S, Klegeris A, Qing H, Mcgeer PL (2011) STAT3 inhibitors attenuate interferon-gamma-induced neurotoxicity and inflammatory molecule production by human astrocytes. Neurobiol Dis 41:299–307PubMed

Hogberg HT, Kinsner-Ovaskainen A, Hartung T, Coecke S, Bal-Price AK (2009) Gene expression as a sensitive endpoint to evaluate cell differentiation and maturation of the developing central nervous system in primary cultures of rat cerebellar granule cells (CGCs) exposed to pesticides. Toxicol Appl Pharmacol 235:268–286PubMed

Hogberg HT, Kinsner-Ovaskainen A, Coecke S, Hartung T, Bal-Price AK (2010) mRNA expression is a relevant tool to identify developmental neurotoxicants using an in vitro approach. Toxicol Sci 113:95–115PubMed

Juarez BI, Martinez ML, Montante M, Dufour L, Garcia E, Jimenez-Capdeville ME (2002) Methylmercury increases glutamate extracellular levels in frontal cortex of awake rats. Neurotoxicol Teratol 24:767–771PubMed

Kershaw TG, Clarkson TW, Dhahir PH (1980) The relationship between blood levels and dose of methylmercury in man. Arch Environ Health 35:28–36PubMed

Kim SR, Park MJ, Lee MK, Sung SH, Park EJ, Kim J, Kim SY, Oh TH, Markelonis GJ, Kim YC (2002) Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate. Free Radic Biol Med 32:596–604PubMed

Kobayashi K (2001) Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. J Investig Dermatol Symp Proc 6:115–121PubMed

Kocot J, Kiełczykowska M, Luchowska-Kocot D, Kurzepa J, Musik I (2018) Antioxidant potential of Propolis, bee pollen, and Royal Jelly: possible medical application. Oxidative Med Cell Longev 2(2018):7074209

Komosinska-Vassev K, Olczyk P, Kaźmierczak J, Mencner L, Olczyk K (2015) Bee pollen: chemical composition and therapeutic application. Evidence-based complementary and alternative medicine:eCAM 2015:297425–297425PubMedPubMedCentral

Kroyer G, Hegedus N (2001) Evaluation of bioactive properties of pollen extracts as functional dietary food supplement. Innovative Food Sci Emerg Technol 2:171–174

Krug AK, Balmer NV, Matt F, Schonenberger F, Merhof D, Leist M (2013) Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants. Arch Toxicol 87:2215–2231PubMed

Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T (2005) Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect 113:894–899PubMedPubMedCentral

Llop S, Tran V, Ballester F, Barbone F, Sofianou-Katsoulis A, Sunyer J, Engstrom K, Alhamdow A, Love TM, Watson GE, Bustamante M, Murcia M, Iniguez C, Shamlayecf RV, Mariuz M, Horvat M, Tratnik JS, Mazej D, Van Wijngaarden E, Davidson PW, Myers GJ, Rand MD, Broberg K (2017) CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment. Environ Int 105:34–42PubMedPubMedCentral

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 91:303–311PubMed

Mbongue JC, Nicholas DA, Torrez TW, Kim NS, Firek AF, Langridge WHR (2015) The role of Indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines 3:703–729PubMedPubMedCentral

Mollgard K, Saunders NR (1986) The development of the human blood-brain and blood-CSF barriers. Neuropathol Appl Neurobiol 12:337–358PubMed

Nagashima K, Fujii Y, Tsukamoto T, Nukuzuma S, Satoh M, Fujita M, Fujioka Y, AKAGI H (1996) Apoptotic process of cerebellar degeneration in experimental methylmercury intoxication of rats. Acta Neuropathol 91:72–77PubMed

Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA, Munday NA, Sayyaparaju MR, Smulson ME, Yamin TT, Yu VL, Miller DK (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43PubMed

Nogueira C, Iglesias A, Feás X, Estevinho LM (2012) Commercial bee pollen with different geographical origins: a comprehensive approach. Int J Mol Sci 13:11173–11187PubMedPubMedCentral

Pascoal A, Rodrigues S, Teixeira A, Feas X, Estevinho LM (2014) Biological activities of commercial bee pollens: antimicrobial, antimutagenic, antioxidant and anti-inflammatory. Food Chem Toxicol 63:233–239PubMed

Qiang-Nan Feng, Xin Liang, Sha Li, and Yan Zhang (2018) The ADAPTOR PROTEIN-3 complex mediates pollen tube growth by coordinating vacuolar targeting and organization. Plant Physiol 177:216–225PubMedPubMedCentral

Rebiai A (2013) Determination of Caffeic Acid and Gallic Acid in Algerian Bee Pollen by an HPLC Method. 1^st Algerian Days on Natural Products, December, Bechar Algeria

Rice D, Barone SJR (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108:S511–S533

Rosa SG, Quines CB, Stangherlin EC, Nogueira CW (2016) Diphenyl diselenide ameliorates monosodium glutamate induced anxiety-like behavior in rats by modulating hippocampal BDNF-Akt pathway and uptake of GABA and serotonin neurotransmitters. Physiol Behav 155:1–8PubMed

Rubin DH, Althoff RR, Ehli EA, Davies GE, Rettew DC, Crehan ET, Walkup JT, Hudziak JJ (2013) Candidate gene associations with withdrawn behavior. J Child Psychol Psychiatry Allied Discip 54:1337–1345

Sakamoto M, Miyamoto K, Wu Z, Nakanishi H (2008) Possible involvement of cathepsin B released by microglia in methylmercury-induced cerebellar pathological changes in the adult rat. Neurosci Lett 442:292–296PubMed

Shanker G, Aschner M (2003) Methylmercury-induced reactive oxygen species formation in neonatal cerebral astrocytic cultures is attenuated by antioxidants. Brain Res Mol Brain Res 110:85–91PubMed

Stejskal V, Ockert K, Bjorklund G (2013) Metal-induced inflammation triggers fibromyalgia in metal-allergic patients. Neuroendocrinol Lett 34:559–565PubMed

Stiles J, Jernigan TL (2010) The basics of brain development. Neuropsychol Rev 20:327–348PubMedPubMedCentral

Strużyńska L, Sulkowski G (2004) Relationships between glutamine, glutamate, and GABA in nerve endings under Pb-toxicity conditions. J Inorg Biochem 98:951–958PubMed

Suñol C, Rodríguez-Farre E (2012) Vitro models for methylmercury neurotoxicity: effects on glutamatergic cerebellar granule neurons. In: Ceccatelli S, Aschner M (eds) Methylmercury and Neurotoxicity. Springer, Boston, pp 259–270

Sweeten TL, Posey DJ, Shankar S, Mcdougle CJ (2004) High nitric oxide production in autistic disorder: a possible role for interferon-gamma. Biol Psychiatry 55:434–437PubMed

Syversen T, Kaur P (2012) The toxicology of mercury and its compounds. J Trace Elem Med Biol 26:215–226PubMed

Takser L, Mergler D, Hellier G, Sahuquillo J, Huel G (2003) Manganese, monoamine metabolite levels at birth, and child psychomotor development. Neurotoxicology 24:667–674PubMed

Tran NQV, Miyake K (2017) Neurodevelopmental disorders and environmental toxicants: epigenetics as an underlying mechanism. Int J Genomics 2017:7526592–7526615PubMedPubMedCentral

Tsuzuki Y (1982) Effect of methylmercury exposure on different neurotransmitter systems in rat brain. Toxicol Lett 13:159–162PubMed

Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Van Geen A, Slavkovich V, Lolacono NJ, Cheng Z, Hussain I (2004) Water arsenic exposure and children's intellectual function in Araihazar, Bangladesh. Environ Health Perspect 112:1329–1333PubMedPubMedCentral

Xue X, Zhao J, Chen L, Zhou J, Yue B, Li Y, Wu L, Liu F (2012) Analysis of coenzyme Q10 in bee pollen using online cleanup by accelerated solvent extraction and high performance liquid chromatography. Food Chem 133:573–578PubMed

Yang CJ, Tan HP, Du YJ (2014) The developmental disruptions of serotonin signaling may involved in autism during early brain development. Neuroscience 267:1–10PubMed

Yildiz O, Can Z, Saral O, Yuluğ E, Ozturk F, Aliyazicioğlu R, Canpolat S, Kolayli S (2013) Hepatoprotective potential of chestnut bee pollen on carbon tetrachloride-induced hepatic damages in rats. Evidence-based complementary and alternative medicine:eCAM 2013:461478–461478PubMedPubMedCentral

Zareba G, Cernichiari E, Hojo R, Nitt SM, Weiss B, Mumtaz MM, Jones D, Clarkson TW (2007) Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury. J Appl Toxicol 27:511–518PubMed

Title: The therapeutic and protective effects of bee pollen against prenatal methylmercury induced neurotoxicity in rat pups
Authors: Abir Ben Bacha
Al-Orf Norah
May Al-Osaimi
Abdel Halim Harrath
Lamjed Mansour
Afaf El-Ansary
Publication date: 01-01-2020
Publisher: Springer US
Keyword: Interferon
Published in: Metabolic Brain Disease / Issue 1/2020
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-019-00496-z

At a glance: The STEP trials

Springer Medicine

The therapeutic and protective effects of bee pollen against prenatal methylmercury induced neurotoxicity in rat pups

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Prior exercise protects against oxidative stress and motor deficit in a rat model of Parkinson’s disease

Preclinical and clinical research on the toxic and neurological effects of cassava (Manihot esculenta Crantz) consumption

Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats

Profiling of differentially expressed circular RNAs in peripheral blood mononuclear cells from Alzheimer’s disease patients

The role of non-coding RNAs in neuroprotection and angiogenesis following ischemic stroke

Passiflora caerulea L. fruit extract and its metabolites ameliorate epileptic seizure, cognitive deficit and oxidative stress in pilocarpine-induced epileptic mice