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However, its iatrogenic molecular mechanism and the rescue therapy are disregarded. Recently, it has been demonstrated that sodium butyrate (NaB) reduces hepatic steatosis, improving respiratory capacity and mitochondrial dysfunction in obese mice. Here, we investigated the protective effect of NaB in counteracting VPA\u2010induced hepatotoxicity using in vitro and in vivo models. Human HepG2 cells and primary rat hepatocytes were exposed to high VPA concentration and treated with NaB. Mitochondrial function, lipid metabolism, and oxidative stress were evaluated, using Seahorse analyzer, spectrophotometric, and biochemical determinations. Liver protection by NaB was also evaluated in VPA\u2010treated epileptic WAG\/Rij rats, receiving NaB for 6\u00a0months. NaB prevented VPA toxicity, limiting cell oxidative and mitochondrial damage (ROS, malondialdehyde, SOD activity, mitochondrial bioenergetics), and restoring fatty acid oxidation (peroxisome proliferator\u2010activated receptor \u03b1 expression and carnitine palmitoyl\u2010transferase activity) in HepG2 cells, primary hepatocytes, and isolated mitochondria. In vivo, NaB confirmed its activity normalizing hepatic biomarkers, fatty acid metabolism, and reducing inflammation and fibrosis induced by VPA. These data support the protective potential of NaB on VPA\u2010induced liver injury, indicating it as valid therapeutic approach in counteracting this common side effect due to VPA chronic treatment.<\/jats:p>","DOI":"10.1096\/fj.201900927rr","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T04:39:38Z","timestamp":1574743178000},"page":"676-690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Butyrate prevents valproate\u2010induced liver injury: In vitro and in vivo evidence"],"prefix":"10.1096","volume":"34","author":[{"given":"Claudio","family":"Pirozzi","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Lama","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II Naples 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