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Valproic acid (VPA) is among the FS\u2010inducing drugs. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in VPA\u2010induced renal injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Animals received VPA (250 and 500\u00a0mg\/kg, i.p., 15 consecutive days). Serum biomarkers of kidney injury and markers of oxidative stress were assessed. Moreover, kidney mitochondria were isolated and mitochondrial indices, including succinate dehydrogenase activity (SDA), mitochondrial depolarization, mitochondrial permeability transition pore (MPP), reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial glutathione, and ATP were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Valproic acid\u2010treated animals developed biochemical evidence of FS as judged by elevated serum gamma\u2010glutamyl transferase (\u03b3\u2010GT), alkaline phosphatase (ALP), creatinine (Cr), and blood urea nitrogen (BUN) along with hypokalaemia, hypophosphataemia, and a decrease in serum uric acid. VPA caused an increase in kidney ROS and LPO. Renal GSH reservoirs were depleted and tissue antioxidant capacity decreased in VPA\u2010treated animals. Renal tubular interstitial nephritis, tissue necrosis, and atrophy were also evident in VPA\u2010treated rats. Mitochondrial parameters including SDA, MMP, GSH, ATP and MPP were decreased and mitochondrial ROS and LPO were increased with VPA treatment. It was found that carnitine (100\u00a0mg\/kg, i.p.) mitigated VPA adverse effects towards the kidney.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that mitochondrial dysfunction and oxidative stress contributed to the VPA\u2010induced FS. On the other hand, carnitine could be considered a potentially safe and effective therapeutic option in attenuating VPA\u2010induced renal injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.13012","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T18:53:02Z","timestamp":1485888782000},"page":"351-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Mechanism of valproic acid\u2010induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-9838","authenticated-orcid":false,"given":"Reza","family":"Heidari","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faezeh","family":"Jafari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forouzan","family":"Khodaei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Shirazi Yeganeh","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Niknahad","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Department of Pharmacology and Toxicology, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.06.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-008055232-3.62642-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004670000535"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.05504.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(02)00447-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00709-015-0796-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513819309048273"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.12.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004670000535"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hct258"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0841-x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602530600959433"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.644535"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650902752376"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.07.056"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21667"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1734-1140(13)70971-X"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409786102"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6969"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/0886022X.2015.1096731"},{"key":"e_1_2_7_22_1","first-page":"21","article-title":"Effects of Enzyme Induction and\/or Glutathione Depletion on Methimazole\u2010Induced Hepatotoxicity in Mice and the Protective Role of N\u2010Acetylcysteine","volume":"4","author":"Heidari R","year":"2014","journal-title":"Adv. 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