{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:47:27Z","timestamp":1791967647695,"version":"4.3.4"},"reference-count":35,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Phenytoin is an anticonvulsant medication that is effective in treating various seizure disorders. It is mostly metabolized by the liver, which increases the risk of PHT-induced hepatotoxicity. Aims This study aimed to assess the effectiveness of N-acetylcysteine (NAC) in protecting the liver from phenytoin-induced hepatotoxicity in rats. Materials and Methods Four sets of five rats male Wistar albino rats (Rattus norvegicus) used for this study was based on their availability, well-established physiology, and long history of use in pharmacological and toxicological studies each were used for analysis. Each of the four groups received different treatments: the control group received normal saline, one group received 200 mg\/kg\/day of NAC, another group received 5 mg\/kg\/day of phenytoin, and the fourth group received 200 mg\/kg\/day of both phenytoin and NAC. The treatments were administered orally by gavage for 45 days. Biochemical indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB)) were measured in serum after the animals were anaesthetized and the experiment ended. Histological analysis was performed on liver specimens. Results Our investigation showed that phenytoin significantly elevated liver enzymes and total serum bilirubin compared to the control and NAC groups. The concurrent administration of NAC and phenytoin led to a notable reduction in these biomarkers, excluding ALP levels. Moreover, the group that received NAC alone did not exhibit a significant increase in the levels of these biomarkers compared with the control group. The histopathological results were in agreement with the biochemical tests. Conclusion This study concluded that Concomitant administration of NAC and phenytoin lowered the risk of phenytoin-induced hepatotoxicity. Moreover, this study confirmed that NAC is relatively safe when administered for a relatively prolonged period.<\/ns3:p>","DOI":"10.12688\/f1000research.163160.1","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T07:25:16Z","timestamp":1753773916000},"page":"593","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatoprotective potential of N-acetyl cysteine in rats with phenytoin induced liver injury"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-0579","authenticated-orcid":false,"given":"Noor D.","family":"Aziz","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Kerbala Kerbala College of Pharmacy, University of Kerbala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deema Diyaa","family":"Azeez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Kerbala College of pharmacy, University of Kerbala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0395-1509","authenticated-orcid":false,"given":"Amal Umran","family":"Mosa","sequence":"additional","affiliation":[{"name":"Department of pharmacology and toxicology, Kerbala College of pharmacy, University of Kerbala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa Abed","family":"Al-kareem","sequence":"additional","affiliation":[{"name":"Department of pharmacology and therapeutics Kufa Faculty of medicine, Kufa University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar A.","family":"Majeed","sequence":"additional","affiliation":[{"name":"Department of pharmacology and therapeutics Kufa Faculty of medicine, Kufa University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadhaa Abdulameer","family":"Ghafil","sequence":"additional","affiliation":[{"name":"Department of pharmacology and therapeutics Kufa Faculty of medicine, Kufa University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"156-164","DOI":"10.1016\/j.seizure.2005.12.009","article-title":"Antiepileptic drugs and liver disease.","volume":"15","author":"S Ahmed","year":"2006","journal-title":"Seizure."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13-18","DOI":"10.1177\/106002808902300102","article-title":"Phenytoin hepatotoxicity: a review of the literature.","volume":"23","author":"M Smythe","year":"1989","journal-title":"DICP."},{"key":"ref3","first-page":"198-204","article-title":"Reversal of phenytoin induced hepatotoxicity by alpha lipoic acid in rats.","volume":"9","author":"G Saraswathy","year":"2015","journal-title":"Afr. 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