{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:47:41Z","timestamp":1790362061556,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Nutrients"],"abstract":"<jats:p>Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC\u2013MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin\u2019s potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.<\/jats:p>","DOI":"10.3390\/nu14040841","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T20:25:45Z","timestamp":1645129545000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses"],"prefix":"10.3390","volume":"14","author":[{"given":"Naglaa","family":"Ammar","sequence":"first","affiliation":[{"name":"Therapeutic Chemistry Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Hassan","sequence":"additional","affiliation":[{"name":"Therapeutic Chemistry Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Afifi","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7060-0077","authenticated-orcid":false,"given":"Abdelbaset","family":"Elgamal","sequence":"additional","affiliation":[{"name":"Chemistry of Microbial and Natural Products Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel","family":"Farrag","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2435-7448","authenticated-orcid":false,"given":"Abd","family":"El-Gendy","sequence":"additional","affiliation":[{"name":"Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5139-1863","authenticated-orcid":false,"given":"Mohamed","family":"Farag","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo 11562, Egypt"},{"name":"School of Forestry and Biotechnology, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-3623","authenticated-orcid":false,"given":"Abdelsamed","family":"Elshamy","sequence":"additional","affiliation":[{"name":"Chemistry of Natural Compounds Department, Pharmaceutical and Drugs Research Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.22034","article-title":"Liver: An organ with predominant innate immunity","volume":"47","author":"Gao","year":"2008","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Al-Seeni, M.N., El Rabey, H.A., Zamzami, M.A., and Alnefayee, A.M. 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