{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:07:37Z","timestamp":1760148457581,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T00:00:00Z","timestamp":1682726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016231","name":"Statutory Activity of Maria Curie-Sklodowska University","doi-asserted-by":"publisher","award":["MN-2021-11"],"award-info":[{"award-number":["MN-2021-11"]}],"id":[{"id":"10.13039\/501100016231","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Maria Curie-Sklodowska University","award":["MN-2021-11"],"award-info":[{"award-number":["MN-2021-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2019 (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\u2032AMP-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.<\/jats:p>","DOI":"10.3390\/molecules28093810","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:12:11Z","timestamp":1682943131000},"page":"3810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8772-3225","authenticated-orcid":false,"given":"Mateusz","family":"Pier\u00f3g","sequence":"first","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-2080","authenticated-orcid":false,"given":"Katarzyna","family":"Soca\u0142a","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-7343","authenticated-orcid":false,"given":"Dorota","family":"Nieoczym","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"Wyska","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2135-701X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Samorek-Pier\u00f3g","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Invasive Diseases, National Veterinary Research Institute, Partyzant\u00f3w Avenue 57, 24-100 Pu\u0142awy, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-0241","authenticated-orcid":false,"given":"Piotr","family":"Wla\u017a","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Sk\u0142odowska University, Akademicka 19, 20-033 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107855","DOI":"10.1016\/j.neuropharm.2019.107855","article-title":"Why we urgently need improved epilepsy therapies for adult patients","volume":"170","author":"Billakota","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0140-6736(14)60456-6","article-title":"Epilepsy: New advances","volume":"385","author":"Moshe","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1542\/peds.2006-2447","article-title":"The ketogenic diet: One decade later","volume":"119","author":"Freeman","year":"2007","journal-title":"Pediatrics"},{"key":"ref_4","first-page":"307","article-title":"The effects of ketonemia on the course of epilepsy","volume":"2","author":"Wilder","year":"1921","journal-title":"Mayo Clin. 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