{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:31:49Z","timestamp":1791567109233,"version":"4.3.4"},"reference-count":79,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Valproic acid (VPA) is a commonly used anticonvulsant prescribed for various neurological disorders. Adverse effects may arise from chronic use and high dosages. This study aims to evaluate the protective effects of L\u2010arginine and Filgrastim against the harmful impact of VPA on gastric and lingual mucosa. Forty male albino rats were divided into four groups (10 for each). The control group received saline, while the VPA group administered VPA (500\u2009mg\/kg) orally for 14\u2009days. The VPA\u2009+\u2009L\u2010arginine and VPA\u2009+\u2009Filgrastim groups received L\u2010arginine (300\u2009mg\/kg) and Filgrastim (40 \u03bcg\/kg), respectively, starting 3\u2009days prior to VPA administration and continued concurrently with VPA for 14\u2009days. Results revealed that VPA caused a decrease in gastric and lingual malondialdehyde (MDA) and superoxide dismutase (SOD) levels, tissue damage, and ulceration in the gastric mucosa. Lingual papillae appeared atrophied. A significant reduction in gastric mucosal thickness, parietal cell number, and fungiform papillae height was found, while the fungiform papillae width was significantly increased. Increased caspase\u20103 reaction in the parietal and chief cells of the gastric mucosa, as well as in the filiform and fungiform papillae of the tongue, was observed. The VPA\u2009+\u2009L\u2010arginine and VPA\u2009+\u2009Filgrastim groups showed improvement in gastric and tongue biochemical and histological abnormalities, with a marked decrease in the caspase\u20103 reaction in gastric tissue. In the VPA\u2009+\u2009Filgrastim group, only the tongue tissue showed decreased caspase\u20103 reaction. It can be concluded that L\u2010arginine and Filgrastim demonstrated effective protection of gastric and lingual mucosa against VPA\u2010induced damage.<\/jats:p>","DOI":"10.1002\/jat.70085","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:41:43Z","timestamp":1771375303000},"page":"3146-3163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective Effect of L\u2010Arginine and Filgrastim Against Valproic Acid\u2013Induced Histopathological Changes on the Gastric and Lingual Mucosa"],"prefix":"10.1002","volume":"46","author":[{"given":"Salwa\u00a0M.","family":"Ouies","sequence":"first","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-2664","authenticated-orcid":false,"given":"Yahia\u00a0A.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Theriogenology, Faculty of Veterinary Medicine Aswan University  Aswan Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha\u00a0A.","family":"Ragab","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"I","given":"Walaa\u00a0I","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine Sohag University  Sohag Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha\u00a0Abd\u2010El\u00a0Baki","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine Qena University  Qena Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000545172"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.21608\/svuijm.2025.409665.2229"},{"key":"e_1_2_10_4_1","first-page":"111","article-title":"Effect of L\u2010Arginine and Carvedilol on Peptic Ulcer and Hypertension in Rats","volume":"39","author":"Abu\u2010Raia N.","year":"2022","journal-title":"Benha Medical Journal"},{"issue":"1","key":"e_1_2_10_5_1","first-page":"52","article-title":"Evaluation of the Cytotoxicity Effect of Sodium Valproate on Wistar Rats","volume":"4","author":"Adam S.","year":"2020","journal-title":"Neelain Journal of Science and Technology"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.21608\/svuijm.2024.324368.1985"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp-2020-0307"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.13005\/bpj\/938"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-23047-2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-55950-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-025-00614-5"},{"issue":"11","key":"e_1_2_10_12_1","article-title":"Massive Valproic Acid Overdose With Confirmed Pharmacobezoar Formation and Neuromuscular Toxicity: a Case Report and Literature Review","volume":"17","author":"Alrazooqi M. 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