Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment

Bibliographic Details
Title: Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment
Authors: Mateusz Pieróg, Katarzyna Socała, Dorota Nieoczym, Elżbieta Wyska, Małgorzata Samorek-Pieróg, Piotr Wlaź
Source: Molecules, Vol 28, Iss 9, p 3810 (2023)
Publisher Information: MDPI AG, 2023.
Publication Year: 2023
Collection: LCC:Organic chemistry
Subject Terms: caproic acid, caprylic acid, lauric acid, metformin, mice, seizures, Organic chemistry, QD241-441
More Details: In contrast to the other components of the medium-chain triglycerides ketogenic diet (MCT KD), i.e., caprylic acid (CA8), a comprehensive evaluation of caproic (CA6) and lauric acids’ (CA12) properties in standard chemical and electrical seizure tests in mice has not yet been performed. We investigated their effects in maximal electroshock seizure threshold (MEST), 6 Hz seizure threshold and intravenous (i.v.) pentylenetetrazole (PTZ) seizure tests. Since ketone body production can be regulated by the activation of 5′AMP-activated protein kinase (AMPK), we hypothesized that metformin (an AMPK activator) enhance ketogenesis and would act synergistically with the fatty acids to inhibit convulsions. We assessed the effects of acute and chronic co-treatment with metformin and CA6/CA8 on seizures. CA6 and CA12 (p.o.) increased seizure threshold in the 6 Hz seizure test. CA6 at the highest tested dose (30 mmol/kg) developed toxicity in several mice, impaired motor performance and induced ketoacidosis. Acute and chronic co-treatment with metformin and CA6/CA8 did not affect seizure thresholds. Moreover, we observed the pro-convulsive effect of the acute co-administration of CA8 (5 mmol/kg) and metformin (100 mg/kg). Since this co-treatment was pro-convulsive, the safety profile and risk/benefit ratio of MCT KD and metformin concomitant therapy in epileptic patients should be further evaluated.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1420-3049
Relation: https://www.mdpi.com/1420-3049/28/9/3810; https://doaj.org/toc/1420-3049
DOI: 10.3390/molecules28093810
Access URL: https://doaj.org/article/865b190ff2b3427693b829fd7330aba0
Accession Number: edsdoj.865b190ff2b3427693b829fd7330aba0
Database: Directory of Open Access Journals
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More Details
ISSN:14203049
DOI:10.3390/molecules28093810
Published in:Molecules
Language:English