{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:17:48Z","timestamp":1788283068308,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers","award":["PNURSP2023R165"],"award-info":[{"award-number":["PNURSP2023R165"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Paracetamol overdose is a significant global issue due to its widespread use, which can lead to a lack of awareness regarding its potential side effects. Paracetamol can harm the liver, possibly resulting in liver failure. Conversely, this study employed extracts from Petroselinum crispum (PC), known for its rich content of bioactive compounds, with demonstrated antioxidant properties shown in previous research as well as protective effects against various diseases. The primary objective of this study was to investigate the potential protective effects of Petroselinum crispum on altered hematological and biochemical parameters in the blood of rats exposed to paracetamol. Materials and Methods: The study involved twenty Wistar rats divided into four groups. Different groups of male rats were administered PC extract at 200 mg\/kg body weight daily for 15 days, along with a standard reference dose of paracetamol at 200 mg\/kg. The study assessed hepatoprotection capacity by analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profiles. Renal safety was evaluated through creatinine, urea, uric acid, lactate dehydrogenase (LDH), and total protein. Additionally, histopathological examinations of the liver and kidneys were conducted. Results: Following Paracetamol overdose, there were reductions in hemoglobin levels, serum total protein, albumin, and uric acid. Paracetamol overdose also elevated levels of several blood biomarkers, including creatinine, urea, nitrogen, ALT, AST, triglycerides, LDH activity, white blood cell count, and platelet count compared to the control group. However, using an ethanolic extract of Petroselinum crispum significantly mitigated the severity of these alterations and the extent of the effect correlated with the dose administered. Parsley extract helped prevent proteinuria and low hemoglobin, which are common side effects of Paracetamol. Conclusions: Therefore, parsley may hold promise in managing liver and kidney conditions\u2014particularly in addressing proteinuria. Ultimately, these results may have implications for human health by potentially mitigating paracetamol-induced renal, hepatic, and hematological toxicity.<\/jats:p>","DOI":"10.3390\/medicina59101814","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T07:28:44Z","timestamp":1697095724000},"page":"1814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Protective Potential of Petroselinum crispum (Mill.) Fuss. on Paracetamol-Induced Hepatio-Renal Toxicity and Antiproteinuric Effect: A Biochemical, Hematological, and Histopathological Study"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-826X","authenticated-orcid":false,"given":"Ghizlane","family":"Nouioura","sequence":"first","affiliation":[{"name":"Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El-Mehraz, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayeb","family":"Kettani","sequence":"additional","affiliation":[{"name":"Sa\u00e2da Laboratory of Medical Analysis, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryem","family":"Tourabi","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El-Mehraz, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layla Tahiri","family":"Elousrouti","sequence":"additional","affiliation":[{"name":"Departments of Pathology, University Hospital Hassan II, Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4706-4311","authenticated-orcid":false,"given":"Omkulthom","family":"Al kamaly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar Zuhair","family":"Alshawwa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-3196","authenticated-orcid":false,"given":"Abdelaaty A.","family":"Shahat","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-4241","authenticated-orcid":false,"given":"Abdulsalam","family":"Alhalmi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badiaa","family":"Lyoussi","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El-Mehraz, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elhoussine","family":"Derwich","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), Faculty of Sciences Dhar El-Mehraz, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"},{"name":"Unity of GC\/MS and GC, City of Innovation, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1503\/cmaj.1040752","article-title":"Liver enzyme alteration: A guide for clinicians","volume":"172","author":"Giannini","year":"2005","journal-title":"Can. Med. Assoc. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"634","DOI":"10.21608\/jbaar.2016.109005","article-title":"Biochemical and histological studies on the possible protective impact of the herb basil (Ocimum basilicum) on adriamycin induced toxicity in rats. I. Influence on the liver","volume":"2","author":"Bayomy","year":"2016","journal-title":"J. Biosci. Appl. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.biopha.2016.12.038","article-title":"Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: A biochemical, histopathological, and immunohistochemical study","volume":"86","author":"Abdellatief","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","first-page":"779","article-title":"Nanotechnology Based Approach for Hepatocellular Carcinoma Targeting","volume":"22","author":"Alhalmi","year":"2021","journal-title":"Curr. Drug Targets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/20014091111677","article-title":"Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches","volume":"31","author":"Bessems","year":"2001","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4162\/nrp.2018.12.6.535","article-title":"Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats","volume":"12","author":"Lyoussi","year":"2018","journal-title":"Nutr. Res. Pract."},{"key":"ref_7","first-page":"113","article-title":"Study of The Anti-Inflammatory Activity of Some Medicinal Edible Plants Growing in Egypt","volume":"10","author":"Ammar","year":"1997","journal-title":"Med. J. Islam. Acad. Sci."},{"key":"ref_8","first-page":"17","article-title":"The Effect Of The Aqueous Extract Of Kohautia Grandiflora On Paracetamol Induced Liver Damage In Albino Rats","volume":"24","author":"Garba","year":"2009","journal-title":"Niger. J. Physiol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1021\/tx300279f","article-title":"Locally Weighted Learning Methods for Predicting Dose-Dependent Toxicity with Application to the Human Maximum Recommended Daily Dose","volume":"25","author":"Liu","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3844\/ajptsp.2006.17.20","article-title":"Hepatoprotective Activity of Aqueous Ethanolic Extract of Chamomile capitula in Paracetamol Intoxicated Albino Rats","volume":"1","author":"Gupta","year":"2006","journal-title":"Am. J. Pharmacol. Toxicol."},{"key":"ref_11","first-page":"65","article-title":"Effect of Paracetamol (Acetaminophen) on Haematological and Reproductive Parameters in Male Albino Rats","volume":"4","author":"Oyedeji","year":"2013","journal-title":"IOSR J. Pharm. Biol. Sci."},{"key":"ref_12","first-page":"135","article-title":"Paracetamol-induced changes of haematobiochemical and oxidative stress parameters in rat blood: Protective role of vitamin C and \u03b2-glucan","volume":"38","author":"Milosevic","year":"2016","journal-title":"Kragujev. J. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.reaurg.2007.08.004","article-title":"Foie toxique: M\u00e9canismes l\u00e9sionnels et th\u00e9rapeutiques pharmacologiques sp\u00e9cifiques","volume":"16","author":"Megarbane","year":"2007","journal-title":"R\u00e9animation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.foodchem.2008.04.060","article-title":"Water-extractable phytochemicals from Phyllanthus niruri exhibit distinct in vitro antioxidant and in vivo hepatoprotective activity against paracetamol-induced liver damage in mice","volume":"111","author":"Sabir","year":"2008","journal-title":"Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1093\/qjmed\/95.9.609","article-title":"Paracetamol toxicity: Epidemiology, prevention and costs to the health-care system","volume":"95","author":"Sheen","year":"2002","journal-title":"Qjm Int. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113209","DOI":"10.1016\/j.jep.2020.113209","article-title":"Protective effects of Glycyrrhiza glabra supplementation against methotrexate-induced hepato-renal damage in rats: An experimental approach","volume":"263","author":"Chauhan","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","first-page":"918","article-title":"In Vivo Study on Hepatoprotective Potential of Nagdantyadi Ghrita in Paracetamol Induced Hepa-totoxicity in Wistar Rats","volume":"11","author":"Gawai","year":"2022","journal-title":"World J. Pharm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ghareeb, M.A., Sobeh, M., El-Maadawy, W.H., Mohammed, H.S., Khalil, H., Botros, S., and Wink, M. (2019). Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato\u2013Renal Protective Potential against Cyclophosphamide Induced Toxicity in Mice. Antioxidants, 8.","DOI":"10.3390\/antiox8090415"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Streba, C.-T., Rogoveanu, I., and Vere, C.C. (2022). Hepatotoxicity, IntechOpen. Chapter 3.","DOI":"10.5772\/intechopen.98062"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.53730\/ijhs.v6nS2.5173","article-title":"Attenuation of paracetamol induced hepatotoxicity by Albizia odoratissima in rats","volume":"6","author":"Byna","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"ref_21","first-page":"10","article-title":"Dengue and its association with hepatic biomarkers: Antiinflammatory action and utilization of paracetamol as a hepatotoxicity factor","volume":"3","author":"Mateus","year":"2022","journal-title":"Braz. J. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nouioura, G., Tourabi, M., El Ghouizi, A., Kara, M., Assouguem, A., Saleh, A., Al Kamaly, O., El Ouadrhiri, F., Lyoussi, B., and Derwich, E.H. (2023). Optimization of a New Antioxidant Formulation Using a Simplex Lattice Mixture Design of Apium graveolens L., Coriandrum sativum L., and Petroselinum crispum M. Grown in Northern Morocco. Plants, 12.","DOI":"10.3390\/plants12051175"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e20201408","DOI":"10.1590\/0001-3765202320201408","article-title":"Fisetin Attenuates Paracetamol-Induced Hepatotoxicity by Regulating CYP2E1 Enzyme","volume":"95","author":"Ugan","year":"2023","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.9734\/EJMP\/2014\/7238","article-title":"The Protective Effect of Coriandium sativum Extract on Hepato-renal Toxicity Induced in Irradiated Rats","volume":"4","author":"Fahmy","year":"2014","journal-title":"Eur. J. Med. Plants"},{"key":"ref_25","first-page":"309","article-title":"Perspectives of the Apiaceae Hepatoprotective Effects\u2014A Review","volume":"12","year":"2017","journal-title":"Nat. Prod. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3923\/pjn.2020.80.85","article-title":"Antioxidant Activities of Parsley (Petroselinum crispum) on the Induced Biochemical and Histopathological Changes of Potassium Bromate-Fed Rats","volume":"19","author":"Waheeba","year":"2020","journal-title":"Pak. J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Emad, A.M., Ali, S.F., Abdel-Rahman, E.A., Meselhy, M.R., Farag, M.A., Ali, S.S., and Abdel-Sattar, E.A. (2020). Anti-inflammatory and antioxidant effects of Apium graveolens L. extracts mitigate against fatal acetaminophen-induced acute liver toxicity. J. Food Biochem., 44.","DOI":"10.1111\/jfbc.13399"},{"key":"ref_28","first-page":"8408326","article-title":"Antidiabetic and Antioxidant Impacts of Desert Date (Balanites aegyptiaca) and Parsley (Petroselinum sativum) Aqueous Extracts: Lessons from Experimental Rats","volume":"2016","author":"Khalil","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_29","first-page":"54","article-title":"Preliminary Evaluation of the Anti-Inflammatory and Anti-Hepatotoxic Activities of \u201cParsley\u201d Petroselinum crispum in Rats","volume":"3","author":"Rafatullah","year":"2003","journal-title":"J. Nat. Remedies"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4274\/balkanmedj.2015.1411","article-title":"Petroselinum crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage","volume":"34","year":"2017","journal-title":"Balk. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/ptr.1598","article-title":"Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: A morphological and biochemical study","volume":"18","author":"Bolkent","year":"2004","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1002\/jsfa.7078","article-title":"Petroselinum crispum has antioxidant properties, protects against DNA damage and inhibits proliferation and migration of cancer cells","volume":"95","author":"Tang","year":"2015","journal-title":"J. Sci. Food Agric."},{"key":"ref_33","first-page":"178","article-title":"Acute and Subacute Toxic Aqueous Extract of the Leaves of Petroselinum crispum Mill. in Male and Female Wistar Rats","volume":"17","author":"Jacques","year":"2021","journal-title":"Eur. Sci. J. ESJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.31579\/2637-8914\/096","article-title":"Processing and Some Phsico-Chemical Properties of White Cheese Made from Camel Milk Using Capparis decidua Fruits Extract As A Coagulant","volume":"5","author":"Ishag","year":"2022","journal-title":"Nutr. Food Process."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/15563650.2017.1317349","article-title":"Risk prediction of hepatotoxicity in paracetamol poisoning","volume":"55","author":"Wong","year":"2017","journal-title":"Clin. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1086\/363177","article-title":"Celery and Parsley as Foods in the Greco-Roman Period","volume":"44","author":"Andrews","year":"1949","journal-title":"Class. Philol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Popiolek, I., Hydzik, P., Jagielski, P., Zrodlowska, M., Mystek, K., and Porebski, G. (2021). Risk Factors for Hepatotoxicity Due to Paracetamol Overdose in Adults. Medicina, 57.","DOI":"10.3390\/medicina57080752"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101701","DOI":"10.1016\/j.jsps.2023.101701","article-title":"Assessment of the acute and subacute toxicity of the aqueous extract of Moroccan Ferula communis fruit in a mouse model","volume":"31","author":"Nouioura","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Coelho, A.M., Queiroz, I.F., Perucci, L.O., de Souza, M.O., Lima, W.G., Talvani, A., and Costa, D.C. (2022). Piperine as Therapeutic Agent in Paracetamol-Induced Hepatotoxicity in Mice. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091800"},{"key":"ref_40","unstructured":"Agyare, C., Appiah, T., Boakye, Y.D., and Apenteng, J.A. (2017). Medicinal Spices and Vegetables from Africa, Academic Press."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Badr, G.M., Algefare, A.I., and Alfwuaires, M.A. (2021). Antioxidant Potential of Parsley Leaf (Petroselinum crispum) Essential Oil on Hypothyroidism and Testicular Injury in Mice Intoxicated by Carbon Tetrachloride. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/9989174"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Thiviya, P., Gunawardena, N., Gamage, A., Madhujith, T., and Merah, O. (2022). Apiaceae Family as a Valuable Source of Biocidal Components and their Potential Uses in Agriculture. Horticulturae, 8.","DOI":"10.3390\/horticulturae8070614"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21608\/jcbr.2020.45551.1077","article-title":"Protective efficiency of parsley (Petroselinum crispum) against oxidative stress, DNA damage and nephrotoxicity induced with anti- tuberculosis drugs","volume":"5","author":"Ashry","year":"2021","journal-title":"Int. J. Cancer Biomed. Res."},{"key":"ref_44","first-page":"173","article-title":"Protective Effects of Petroselinum crispum (Parsley) Extract Against Methotrexate-Induced Hepatotoxicity","volume":"80","author":"Turan","year":"2019","journal-title":"Eur. J. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5937\/arhfarm71-30800","article-title":"A review of botanical characteristics, chemical composition, pharmacological activity and use of parsley","volume":"71","year":"2021","journal-title":"Arh. Za Farm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"385","DOI":"10.17582\/journal.aavs\/2020\/8.4.385.391","article-title":"Mechanisms of Hepato-Renal Protective Activity of Ocimum basilicum Leaf Extract against Paracetamol Toxicity in Rat Model","volume":"8","author":"Soliman","year":"2020","journal-title":"Adv. Anim. Vet. Sci."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1814\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:05:31Z","timestamp":1760130331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["medicina59101814"],"URL":"https:\/\/doi.org\/10.3390\/medicina59101814","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]}}}