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Gallic acid modulates purine metabolism and oxidative stress induced by ethanol exposure in zebrafish brain

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Abstract

Gallic acid (GA) is a secondary metabolite found in plants. It has the ability to cross the blood-brain barrier and, through scavenging properties, has a protective effect in a brain insult model. Alcohol metabolism generates reactive oxygen species (ROS); thus, alcohol abuse has a deleterious effect on the brain. The zebrafish is a vertebrate often used for screening toxic substances and in acute ethanol exposure models. The aim of this study was to evaluate whether GA pretreatment (24 h) prevents the changes induced by acute ethanol exposure (1 h) in the purinergic signaling pathway in the zebrafish brain via degradation of extracellular nucleotides and oxidative stress. The nucleotide cascade promoted by the nucleoside triphosphate diphosphohydrolase (NTPDase) and 5′-nucleotidase was assessed by quantifying nucleotide metabolism. The effect of GA alone at 5 and 10 mg L−1 did not change the nucleotide levels. Pretreatment with 10 mg L−1 GA prevented an ethanol-induced increase in ATP and ADP levels. No significant difference was found between the AMP levels of the two pretreatment groups. Pretreatment with 10 mg L−1 GA prevented ethanol-enhanced lipid peroxidation and dichlorodihydrofluorescein (DCFH) levels. The higher GA concentration was also shown to positively modulate against ethanol-induced effects on superoxide dismutase (SOD), but not on catalase (CAT). This study demonstrated that GA prevents the inhibitory effect of ethanol on NTPDase activity and oxidative stress parameters, thus consequently modulating nucleotide levels that may contribute to the possible protective effects induced by alcohol and purinergic signaling.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article. The raw data are available from Eduardo Pacheco Rico upon reasonable request.

Abbreviations

DCF:

2′,7′-dihydrodichlorofluorescein diacetate

ATP:

Adenosine 5′ triphosphate

CAT:

Catalase

CNS:

Central nervous system

DTNB:

5,5-dithio-bis-(2-nitrobenzoic acid

NTPDase:

Nucleoside triphosphate diphosphohydrolase

SOD:

Superoxide dismutase

TBA-RS:

Thiobarbituric acid-reactive species

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Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) research Grant (Universal 429302/2018-5), Fundação de Amparo à Pesquisa do Estado de Santa Catarina (FAPESC - Universal 12/2020), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES AUXPE PROEX N. 23038.020053/2018-52).

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Authors and Affiliations

  1. Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil

    Samira Leila Baldin, Karolyne de Pieri Pickler, Ana Caroline Salvador de Farias, Henrique Teza Bernardo, Bárbara da Costa Pereira, Suzielen Damin Pacheco, Eduardo Ronconi Dondossola & Eduardo Pacheco Rico

  2. Experimental Physiology Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil

    Rahisa Scussel & Ricardo Andrez Machado-de-Ávila

  3. Department of Pharmaceutical Sciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil

    Almir Gonçalves Wanderley

  4. Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE, Brazil

    Almir Gonçalves Wanderley

  5. Laboratory of Translational Biomedicine Laboratory, University of Southern Santa Catarina (UNESC), Criciuma, Santa Catarina, Brazil

    Eduardo Pacheco Rico

Authors
  1. Samira Leila Baldin
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  11. Eduardo Pacheco Rico
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Contributions

SLB: investigation, validation, data curation, writing - original draft. KPP: conceptualization, concept and design. ACSF: investigation, validation, data curation, writing - original draft. HTB: formal analysis investigation, writing - review and editing. RS: data analysis and interpretation, writing - review and editing. BCP: investigation, validation, data curation. SDP: investigation, validation, data curation. ERD: formal analysis investigation, writing - review & editing. RAM: formal analysis investigation, writing - review and editing. AGW: formal analysis investigation, writing - review and editing. EPR: funding acquisition, project administration, supervision, writing — review and editing, resources. The paper was read, revised, and approved by all the authors.

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Correspondence to Eduardo Pacheco Rico.

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Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The study protocol was approved by the Ethics Committee of University of Southern Santa Catarina (UNESC), Criciúma, Brazil, number 030/2019-1.

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The authors declare no competing interests.

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Highlights

• Gallic acid reduces oxidative stress induced by acute ethanol in the zebrafish brain.

• Gallic acid prevents disruption of NTPDase activity promoted by ethanol.

• Ethanol alters the degradation of extracellular nucleotides in the zebrafish brain.

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Baldin, S.L., de Pieri Pickler, K., de Farias, A.C.S. et al. Gallic acid modulates purine metabolism and oxidative stress induced by ethanol exposure in zebrafish brain. Purinergic Signalling 18, 307–315 (2022). https://doi.org/10.1007/s11302-022-09869-z

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