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Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters

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A Correction to this article was published on 31 August 2018

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Abstract

The present study investigated the therapeutic effects of probiotics on brain intoxication induced by clindamycin and propionic acid (PPA) in hamsters. Fifty golden Syrian hamsters were randomly divided into five experimental groups of ten animals each: (A) control group receiving phosphate buffered saline; (B) oral buffered PPA-treated group being administered with a neurotoxic dose of 250 mg/kg PPA during three days; (C) oral clindamycin-treated group receiving a single dose of 30 mg clindamycin/kg; and (D, E) the two therapeutic groups being administered the same doses of clindamycin and PPA followed by probiotics for three weeks at a daily dose of 0.2 g/kg. Biochemical parameters of energy metabolism and oxidative stress were examined in brain homogenates from all hamsters. The development of pathogenic bacteria was monitored on stool samples from all hamsters. Descriptive changes in fecal microbiota and overgrowth of Clostridium species in clindamycin and PPA treated hamsters were recorded. Interestingly, probiotics were shown effective to restore normal gut microbiota. Clindamycin and PPA treatments caused an elevation in lipid peroxidation and catalase activity, as oxidative stress markers, together with a reduction in GST activity and GSH level. Energy metabolism impairment was ascertained via the activation of creatine kinase and a decrease of lactate dehydrogenase. These findings suggest that bacteria overgrowth caused by PPA and clindamycin was efficient to illustrate signs of neuronal toxicity. The present study indicates that probiotic treatment can improve poor detoxification, oxidative stress, and altered gut microbiota as mechanisms implicated in the etiology of many neurological disorders.

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Change history

  • 31 August 2018

    The original version of this article unfortunately contained a mistake. The family name of the fourth author listed in the title was incorrect, and the correct name is Nadine Moubayed, as noted in the addresses. Her name is now corrected in the author group of this article.

Abbreviations

AUC :

area under the curve

BAP :

Sheep Blood Agar plate

BBB :

blood-brain barrier

CDNB :

1-chloro-2,4-dinitrobenzene

CFU :

Colony-forming unit

CK :

creatine kinase

CNS :

center nerves system

ENS :

enteric nervous system

ETC :

electron transport chain

GI :

gastrointestinal tract

GSH :

glutathione

GST :

glutathione-s-transferase

H 2 O 2 :

hydrogen peroxide

HK :

hexokinase

LDH :

lactate dehydrogenase

MCA :

MacConkey Agar

MD :

malondialdehyde

PPA :

propionic acid

ROC :

Receiver Operating Characteristics

ROS :

reactive oxygen species

SCFA :

Short-Chain Fatty Acids

SDA :

Sabouroud Dextrose agar

References

  • Al-Dbass AM (2014) N-Acetylcysteine reduces the neurotoxic effects of propionic acid in rat pups. J King Saud Univ Sci 26:254–260

    Article  Google Scholar 

  • Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem 42:1032–1040

    Article  CAS  Google Scholar 

  • Amador E, Dorfman LE, Wacker WE (1963) Serum lactic dehydrogenase activity: an analytical assessment of current assays. Clin Chem 12:391–399

    CAS  PubMed  Google Scholar 

  • Amdekar S, Singh V (2016) Lactobacillus acidophilus maintained oxidative stress from reproductive organs in collagen-induced arthritic rats. J Hum Reprod Sci 9:41–46

    Article  CAS  Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  • Bojes HK, Suresh PK, Millis EM, Spitz DR, Sim JE, Kehrer JP (1998) Bcl-2 and Bcl-xL in peroxide-resistant A549 and U87MG cells. Toxicol Sci 42:109–116

    CAS  PubMed  Google Scholar 

  • Borre YE, Moloney RD, Clarke G, Dinan TG, Cryan JF (2014) The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol 817:373–403

    Article  CAS  Google Scholar 

  • Brass EP, Beyerinck RA (1987) Interactions of propionate and carnitine metabolism in isolated rat hepatocytes. Metabolism 36:781–787

    Article  CAS  Google Scholar 

  • Brass EP, Beyerinck RA (1988) Effects of propionate and carnitine on the hepatic oxidation of short- and medium-chain-length fatty acids. Biochem J 250:819–825

    Article  CAS  Google Scholar 

  • Bronstein JM, Farber DB, Wasterlain CG (1992) Regulation of type-II calmodulin kinase: functional implications. Brain Res Brain Res Rev 18:135–147

    Article  Google Scholar 

  • Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A, Ubeda C, Xavier J, Pamer EG (2012) Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis. Infect Immun 80:62–73

    Article  CAS  Google Scholar 

  • Chauhan V, Chauhan A (2006) Oxidative stress in Alzheimer's disease. Pathophysiology 13:195–208

    Article  CAS  Google Scholar 

  • Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, Chauhan V (2011) Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem 117:209–220

    Article  CAS  Google Scholar 

  • Chegwidden WR, Watts DC (1984) Anion activation of monkey muscle creatine kinase. Int J BioChemiPhysics 16:1171–1174

    Article  CAS  Google Scholar 

  • Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10:735–742

    Article  CAS  Google Scholar 

  • Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712

    Article  CAS  Google Scholar 

  • El-Ansary AK, Ben Bacha A, Kotb M (2012) Etiology of autistic features: the persisting neurotoxic effects of propionic acid. J Neuroinflammation 9:74. https://doi.org/10.1186/1742-2094-9-74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Ansary AK, Al-Daihan S, Ben Bacha A, Shaker GH, Al-Ayadhi LY (2013) Comparative study on the protective effect of carnosine and carnitine against pro-inflammatory/pro-oxidant effects of clindamycin and propionic acid administrations to hamsters. Afr J Microbiol Res 7:103–114. https://doi.org/10.5897/AJMR12.1178

    Article  CAS  Google Scholar 

  • El-Ansary A, Bhat RS, Al-Daihan S, Al Dbass AM (2015) The neurotoxic effects of ampicillin-associated gut bacterial imbalances compared to those of orally administered propionic acid in the etiology of persistent autistic features in rat pups: effects of various dietary regimens. Gut Pathog 7:7. https://doi.org/10.1186/s13099-015-0054-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Ansary A, Al-Salem HS, Asma A, Al-Dbass A (2017) Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen. Lipids Health Dis 16:96. https://doi.org/10.1186/s12944-017-0485-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Ansary A, Bacha AB, Bjørklund G, Al-Orf N, Bhat RS, Moubayed N, Abed K (2018) Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin. Metab Brain Dis 33(4):1155–1164

    Article  CAS  Google Scholar 

  • Farmer AD, Randall HA, Aziz Q (2014) It's a gut feeling: how the gut microbiota affects the state of mind. J Physiol 592:2981–2988

    Article  CAS  Google Scholar 

  • Finegold SM (2011) Desulfovibrio species are potentially important in regressive autism. Med Hypotheses 77:270–274

    Article  Google Scholar 

  • Foster JA (2013) Gut feelings: bacteria and the brain. Cerebrum 2013:9

    PubMed  PubMed Central  Google Scholar 

  • Frei B (1994) Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 97:5S–13S discussion 22S-28S

    Article  CAS  Google Scholar 

  • Fung TC, Olson CA, Hsiao EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20:145–155

    Article  CAS  Google Scholar 

  • Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17:259–275

    Article  CAS  Google Scholar 

  • Holdeman LV, Cato EP, Moore WEC (1977) Anaerobe laboratory manual. Anaerobe Laboratory, Virginia Polytechnic Institute and State University, Blacksburg

  • Hunt CR, Sim JE, Sullivan SJ, Featherstone T, Golden W, Von Kapp-Herr C, Hock RA, Gomez RA, Parsian AJ, Spitz DR (1998) Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. Cancer Res 58:3986–3992

    CAS  PubMed  Google Scholar 

  • Itoh K, Mitsuoka T, Sudo K, Suzuki K (1983) Comparison of fecal flora of mice based upon different strains and different housing conditions. Z Versuchstierkd 25:135–146

    CAS  PubMed  Google Scholar 

  • James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611–1617

    Article  CAS  Google Scholar 

  • Kullisaar T, Songisepp E, Aunapuu M, Kilk K, Arend A, Mikelsaar M, Rehema A, Zilmer M (2010) Complete glutathione system in probiotic Lactobacillus fermentum ME-3. Prikl Biokhim Mikrobiol 46:527–531

    CAS  PubMed  Google Scholar 

  • Lee JS, Chung MJ, Seo JG (2013) In vitro evaluation of antimicrobial activity of lactic acid bacteria against clostridium difficile. Toxicol Res 29:99–106

    Article  Google Scholar 

  • MacFabe DF, Rodríguez-Capote K, Hoffman JE, Franklin AE, Mohammad-Asef Y, Roy Taylor A, Boon F, Cain DP, Kavaliers M, Possmayer F, Ossenkopp KP (2008) A novel rodent model of autism: Intraventricular infusions of propionic acid increase locomotor activity and induce neuroinflammation and oxidative stress in discrete regions of adult rat brain. Am J Biochem Biotechnol 4:146–166

    Article  CAS  Google Scholar 

  • Maehly AC, Chance B (1954) The assay of catalases and peroxidases. Methods Biochem Anal 1:357–424

    CAS  PubMed  Google Scholar 

  • Mayer EA (2011) Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 12:453–466

    Article  CAS  Google Scholar 

  • Monks TJ, Ghersi-Egea JF, Philbert M, Cooper AJ, Lock EA (1999) Symposium overview: the role of glutathione in neuroprotection and neurotoxicity. Toxicol Sci 51:161–177

    Article  CAS  Google Scholar 

  • Nakao S, Fujii A, Niederman R (1992) Alteration of cytoplasmic Ca2+ in resting and stimulated human neutrophils by short-chain carboxylic acids at neutral pH. Infect Immun 60:5307–5311

    CAS  PubMed  PubMed Central  Google Scholar 

  • O'Mahony SM, Hyland NP, Dinan TG, Cryan JF (2011) Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology 214:71–88

    Article  CAS  Google Scholar 

  • Rhee SH, Pothoulakis C, Mayer EA (2009) Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6:306–314

    Article  CAS  Google Scholar 

  • Roberfroid M (2007) Prebiotics: the concept revisited. J Nutr 137:830S–837S

    Article  CAS  Google Scholar 

  • Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, De Groot H (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59:383–388

    Article  CAS  Google Scholar 

  • Shen Q, Shang N, Li P (2011) In vitro and in vivo antioxidant activity of Bifidobacterium animalis 01 isolated from centenarians. Curr Microbiol 62:1097–1103

    Article  CAS  Google Scholar 

  • Sunenshine RH, McDonald LC (2006) Clostridium difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med 73:187–197

    Article  Google Scholar 

  • Szasz G, Gruber W, Bernt E (1976) Creatine kinase in serum: 1. Determination of optimum reaction conditions. Clin Chem 22:650–656

    CAS  PubMed  Google Scholar 

  • Sziray N, Leveleki C, Levay G, Markó B, Hársing LG Jr, Mikics E, Barsy B, Haller J (2007) Mechanisms underlying the long-term behavioral effects of traumatic experience in rats: the role of serotonin/noradrenaline balance and NMDA receptors. Brain Res Bull 71:376–385

    Article  CAS  Google Scholar 

  • Vahdatpour T, Nikpiran H, Babazadeh D, Vahdatpour S, Jafargholipour MA (2011) Effects of Protexin®, Fermacto® and combination of them on blood enzymes and performance of Japanese quails (Coturnix Japonica). Ann Biol Res 2:283–291

    Google Scholar 

  • Vontas JG, Enayati AA, Small GJ, Hemingway J (2000) A simple biochemical assay for glutathione S-transferase activity and its possible field application for screening glutathione S-transferase-based insecticide resistance. Pestic Biochem Physiol 68:184–192

    Article  CAS  Google Scholar 

  • Wajner M, Latini A, Wyse AT, Dutra-Filho CS (2004) The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies. J Inherit Metab Dis 27:427–448

    Article  CAS  Google Scholar 

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Acknowledgments

This research project was supported by a grant from the Research Center of the Female Scientific and Medical Colleges, Deanship of Scientific Research, King Saud University.

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Correspondence to Geir Bjørklund.

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The authors declare no potential conflicts of interest with respect to the authorship, and/or publication of this article.

Ethical approval

This study was ethically approved by the Ethical Committee, College of Science, King Saud University.

Additional information

The original version of this article was revised: The family name of the fourth author listed in the title was incorrect, and the correct name is Nadine Moubayed, as noted in the addresses. Her name is now corrected in the author group of this article.

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Al-Orf, N., El-Ansary, A., Bjørklund, G. et al. Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters. Metab Brain Dis 33, 1811–1820 (2018). https://doi.org/10.1007/s11011-018-0284-5

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