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Dietary interventions, including the use of ketogenic diets, have been explored for their potential to reduce the adverse effects of hyperglycemia. \u03b2-Hydroxybutyrate (BHB), a ketone body, has immune and anti-inflammatory properties. This study aims to investigate whether BHB ameliorates the harmful effects induced by high glucose in ARPE-19 cells, a model of retinal pigment epithelium. We investigated the effects induced by high glucose and\/or BHB on viability, migration, colony-forming ability, cell cycle progression and cytokine production. Our data indicate that high glucose significantly reduces the viability of ARPE-19 cells with no significant changes in apoptosis or autophagy, while inducing cell cytostasis. On the other hand, BHB exerts a protective effect on ARPE-19 cells under hyperglycemic conditions improving cell viability and alleviating glucose-induced cell cycle arrest. Additionally, BHB treatment affects the expression of IL-8 and IL-17\u03b1, as well as of MCP-1, modulating the inflammatory response, cell migration and wound healing. In conclusion, this study highlights the potential protective role of BHB against the detrimental effects induced by high glucose on ARPE-19 cells. These findings support the use of ketone bodies in mitigating high glucose-induced cellular damage. Future research will be critical to translate these findings to the clinical practice for metabolic diseases.<\/jats:p>","DOI":"10.1007\/s13577-025-01187-x","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T14:05:47Z","timestamp":1740060347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u03b2-Hydroxybutyrate mitigates the detrimental effects of high glucose in human retinal pigment epithelial ARPE-19 cells"],"prefix":"10.1007","volume":"38","author":[{"given":"Francesca","family":"Argentino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Mallardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciro","family":"Costagliola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-9737","authenticated-orcid":false,"given":"Aurora","family":"Daniele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ersilia","family":"Nigro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"1187_CR1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/43603","author":"RA Kowluru","year":"2007","unstructured":"Kowluru RA, Chan P-S. 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