{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:36:04Z","timestamp":1788914164344,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (\u2642\/\u2640 = 1). The control group was treated orally with distilled water (10 mL\/kg); the GM treated group received distilled water (10 mL\/kg) and an intraperitoneal injection of GM (80 mg\/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg\/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants\/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.<\/jats:p>","DOI":"10.3390\/molecules26164806","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:35:40Z","timestamp":1628458540000},"page":"4806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-2470","authenticated-orcid":false,"given":"Noureddine","family":"Bencheikh","sequence":"first","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Bouhrim","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-8916","authenticated-orcid":false,"given":"Loubna","family":"Kharchoufa","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4706-4311","authenticated-orcid":false,"given":"Omkulthom Mohamed","family":"Al Kamaly","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-9089","authenticated-orcid":false,"given":"Hamza","family":"Mechchate","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agrifood and Health, Faculty of Sciences, University of Sidi Mohamed Ben Abdellah, Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-3045","authenticated-orcid":false,"given":"Imane","family":"Es-safi","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology, Environment, Agrifood and Health, Faculty of Sciences, University of Sidi Mohamed Ben Abdellah, Fez 30050, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Dahmani","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabir","family":"Ouahhoud","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soufiane","family":"El Assri","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Mohammed First University, B.P. 724, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-2690","authenticated-orcid":false,"given":"Bruno","family":"Eto","sequence":"additional","affiliation":[{"name":"Laboratories-TBC, Faculty of Pharmaceutical and Biological Sciences, B.P. 83, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Bnouham","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Choukri","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Mohammed First University, B.P. 724, Oujda 60000, Morocco"},{"name":"Biochemistry Laboratory, Central Laboratory Service\u2014CHU, Mohammed VI University Hospital, B.P. 4806, Oujda 60049, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Elachouri","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60040, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biopha.2016.11.117","article-title":"Nephro-Protective Effect of a Novel Formulation of Unopened Coconut Inflorescence Sap Powder on Gentamicin Induced Renal Damage by Modulating Oxidative Stress and Inflammatory Markers","volume":"85","author":"Jose","year":"2017","journal-title":"Biomed. 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