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Effect of a Ketogenic Diet on Oxidative Posttranslational Protein Modifications and Brain Homogenate Denaturation in the Kindling Model of Epilepsy in Mice

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Abstract

This study focused on the ketogenic diet (KD) effects on oxidative posttranslational protein modification (PPM) as presumptive factors implicated in epileptogenesis. A 28-day of KD treatment was performed. The corneal kindling model of epileptogenesis was used. Four groups of adult male ICR mice (25–30 g) were randomized in standard rodent chow (SRC) group, KD-treatment group; SRC + kindling group; KD + kindling group (n = 10 each). Advanced oxidation protein products (AOPP) and protein carbonyl contents of brain homogenates together with differential scanning calorimetry (DSC) were evaluated. Two exothermic transitions (Exo1 and Exo2) were explored after deconvolution of the thermograms. Factor analysis was applied. The protective effect of KD in the kindling model was demonstrated with both decreased seizure score and increased seizure latency. KD significantly decreased glucose and increased ketone bodies (KB) in blood. Despite its antiseizure effect, the KD increased the AOPP level and the brain proteome's exothermic transitions, suggestive for qualitative modifications. The ratio of the two exothermic peaks (Exo2/Exo1) of the thermograms from the KD vs. SRC treated group differed more than twice (3.7 vs. 1.6). Kindling introduced the opposite effect, changing this ratio to 2.7 for the KD + kindling group. Kindling significantly increased glucose and KB in the blood whereas decreased the BW under the SRC treatment. Kindling decreased carbonyl proteins in the brain irrespectively of the diet. Further evaluations are needed to assess the nature of correspondence of calorimetric images of the brain homogenates with PPM.

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Data Availability Statement

Data will be made available on responsible request.

Abbreviations

AOPP:

Advanced oxidation protein products

BW:

Body weight

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DSC:

Differential scanning calorimetry

GABA:

Gamma-aminobutyric acid

GI:

Glycemic index

KB:

Ketone bodies

KD:

Ketogenic diet

O-GlcNAc:

O-linked-β-N-acetyl glucosamine

OS:

Oxidative stress

PPM:

Posttranslational protein modification

PTZ:

Pentylenetetrazole

RAGE:

Receptor for an advanced glycation end product

SRC:

Standard rodent chow

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Acknowledgements

The authors express their gratitude to Mr. Y. Ivanov for the technical support of the DSC apparatus.

Funding

This work was supported by the Bulgarian National Science Fund (grants DN03/13/2016 and DN13/16/2017) and the Medical Science Council of Medical University-Sofia (grant D-211/2018).

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University of Sofia, 1, Georgi Sofiiski Str., 1431, Sofia, Bulgaria

    Pavlina Andreeva-Gateva

  2. Department of Pathophysiology, Faculty of Medicine, Medical University of Sofia, Sofia, Bulgaria

    Zafer Sabit, Dimitar Bakalov & Radka Tafradjiiska-Hadjiolova

  3. Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, Nicosia, Northern Cyprus

    Serkan Sayiner

  4. Department of Medical Physics and Biophysics, Faculty of Medicine, Medical University of Sofia, Sofia, Bulgaria

    Stella Zaharinova, Silviya Abarova & Boris Tenchov

  5. Ohio State University College of Pharmacy, Columbus, OH, USA

    Rumiana Koynova

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Contributions

PAG and BT designed the study, PAG, ZS, RTH, and DB performed the in vivo experiments, ZS and SS conducted the evaluation of AOPP and carbonyl content, SZ and SA conducted the calorimetry of the brain homogenates, RK and BT analyzed the thermograms, PAG performed the statistics and wrote the draft of the manuscript. All authors commented and approved the final variant of the manuscript.

Corresponding author

Correspondence to Pavlina Andreeva-Gateva.

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Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Ethical Approval

The animal models were performed following "The Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals, Washington DC, National Academy Press. An approval N 244/25.9.2019 was received by the Bulgarian Food Safety Agency following the National Regulations. All efforts were made to minimize animal suffering and reduce the number of animals used.

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Andreeva-Gateva, P., Sabit, Z., Bakalov, D. et al. Effect of a Ketogenic Diet on Oxidative Posttranslational Protein Modifications and Brain Homogenate Denaturation in the Kindling Model of Epilepsy in Mice. Neurochem Res 47, 1943–1955 (2022). https://doi.org/10.1007/s11064-022-03579-z

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