{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:25:34Z","timestamp":1762867534338,"version":"3.41.2"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":307,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>The present study is aimed at utilization of novel and classical kidney function biomarkers to evaluate the nephroprotective potential of Carica papaya leaf extract (CPLE) in gentamicin nephrotoxicity model in albino rats. The used classical biomarkers were urea and creatinine; while the new biomarkers were Kidney injury molecule-1 (KIM-1) and Clusterin. Forty-five male albino rats were assigned into five groups and subjected to different treatments for nine consecutive days (vehicles; gentamicin, 100 mg\/kg, subcutaneously; ascorbic acid, 200 mg\/kg, orally; CPLE, 150 and 300 mg\/kg b wt., orally). Three rats\/group were killed on days 3, 6, and 9 for blood and tissue samples for renal and oxidation markers. Gentamicin resulted in significant increase in urea and creatinine only by the end of the experimental course; while the novel biomarkers were evident as early as 3 days upon gentamicin injection. When concurrently administered with gentamicin, CPLE significantly protected kidney tissues against gentamicin nephrotoxic effects indicated by decrement of both the novel and the classical standard biomarkers, in a dose-dependent manner. CPLE-mediated protection was attributed to its antioxidant potential indicated by significant inhibition of malondialdehyde (MDA) levels in both serum and kidney homogenates. The results were further supported by histopathological examination that revealed considerable amelioration of the pathological microscopic alterations induced by repeated gentamicin injection. Phytochemical analysis of CPLE indicated presence of tannins and flavonoids. These data may suggest CPLE, based on improvement of both classical and novel renal markers, as a highly potent nephroprotective and antioxidant from natural source that could be a good remedy in conditions associated with renal disorders.<\/jats:p>","DOI":"10.1042\/bsr20181187","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T19:51:59Z","timestamp":1536695519000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel and classical renal biomarkers as evidence for the nephroprotective effect of<i>Carica papaya<\/i>leaf extract"],"prefix":"10.1042","volume":"38","author":[{"given":"Ibtsam","family":"Gheith","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medinah 344, Kingdom of Saudi Arabia"},{"name":"Department of Biotechnology, Animal Health Research Institute, Dokki 11843, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abubakr","family":"El-Mahmoudy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Benha University Faculty of Veterinary Medicine, Moshtohor 13736, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"2021111619114546300_B1","first-page":"83","article-title":"Creatinine determination according to Jaffe\u2014what does it stand for?","volume":"4","author":"Delanghe","year":"2011","journal-title":"Nephrol. Dial. Transplant. Plus"},{"key":"2021111619114546300_B2","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1001\/archinte.1952.00240120038004","article-title":"Fatal complications of intensive antibiotic therapy in patients with neoplastic disease","volume":"90","author":"Bateman","year":"1952","journal-title":"AMA Arch. Intern. Med."},{"key":"2021111619114546300_B3","first-page":"559","article-title":"Nephrotoxicity testing in vitro\u2013what we know and what we need to know","volume":"106","author":"Pfaller","year":"1998","journal-title":"Environ. Health Perspect."},{"key":"2021111619114546300_B4","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nbt.1625","article-title":"Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium","volume":"28","author":"Dieterle","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2021111619114546300_B5","doi-asserted-by":"crossref","DOI":"10.32473\/edis-fe913-2012","volume-title":"An Overview of Global Papaya Production, Trade, and Consumption","author":"Evans","year":"2012"},{"key":"2021111619114546300_B6","first-page":"1","article-title":"Papaya production in Hawaii","volume":"3","author":"Nishina","year":"2000","journal-title":"Fruits Nuts"},{"key":"2021111619114546300_B7","first-page":"739","article-title":"Wound healing activity of Carica papaya L. in experimentally induced diabetic rats","volume":"45","author":"Nayak","year":"2007","journal-title":"Indian J. Exp. Biol."},{"key":"2021111619114546300_B8","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1089\/jmf.2008.0197","article-title":"Carica papaya (Paw-Paw) unripe fruit may be beneficial in ulcer","volume":"12","author":"Ezike","year":"2009","journal-title":"J. Med. Food"},{"key":"2021111619114546300_B9","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1055\/s-0030-1249859","article-title":"Anti-inflammatory plant natural products for cancer therapy","volume":"76","author":"Aravindaram","year":"2010","journal-title":"Planta Med."},{"key":"2021111619114546300_B10","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.3109\/13880209.2011.596210","article-title":"Effect of ether-and water-soluble fractions of Carica papaya ethanol extract in experimentally induced hyperlipidemia in rats","volume":"49","author":"Iyer","year":"2011","journal-title":"Pharm. Biol."},{"key":"2021111619114546300_B11","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1007\/s12088-011-0086-5","article-title":"Antifungal activity in ethanolic extracts of Carica papaya L. cv. Maradol leaves and seeds","volume":"51","author":"Ch\u00e1vez-Quintal","year":"2011","journal-title":"Indian J. Microbiol."},{"key":"2021111619114546300_B12","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/S2221-1691(11)60055-5","article-title":"Dengue fever treatment with Carica papaya leaves extracts","volume":"1","author":"Ahmad","year":"2011","journal-title":"Asian Pacific J. Trop. Biomed."},{"key":"2021111619114546300_B13","doi-asserted-by":"publisher","first-page":"S306","DOI":"10.1016\/S2222-1808(12)60171-6","article-title":"Antimalarial activity of Carica papaya (Family: Caricaceae) leaf extract against Plasmodium falciparum","volume":"2","author":"Kovendan","year":"2012","journal-title":"Asian Pacific J. Trop. Dis."},{"key":"2021111619114546300_B14","doi-asserted-by":"publisher","first-page":"180","DOI":"10.5455\/aim.2012.20.180-185","article-title":"Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats","volume":"20","author":"Sadek","year":"2012","journal-title":"Acta Inform. Med."},{"key":"2021111619114546300_B15","first-page":"21","article-title":"Thrombocytosis and anti-inflammatory properties and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model","volume":"1","author":"Gammulle","year":"2012","journal-title":"Int. J. Medic. Plant Res."},{"key":"2021111619114546300_B16","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/S2221-1691(13)60145-8","article-title":"Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model","volume":"3","author":"Dharmarathna","year":"2013","journal-title":"Asian Pacific J. Trop. Biomed."},{"key":"2021111619114546300_B17","first-page":"89","article-title":"Antinociceptive and anti-inflammatory studies of the aqueous leaf extract of Carica papaya in laboratory animals","volume":"4","author":"Adedapo","year":"2013","journal-title":"Asian J. Exp. Biol. Sci."},{"key":"2021111619114546300_B18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/mnfr.201200388","article-title":"Anticancer activity of Carica papaya: a review","volume":"57","author":"Nguyen","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"2021111619114546300_B19","first-page":"21","article-title":"Anti-inflammatory, antipyretic and antinociceptive activities of orally administered aqueous extract of Carica papaya seeds in animal models","volume":"2","author":"Umana","year":"2014","journal-title":"Ann. Exp. Bio."},{"key":"2021111619114546300_B20","first-page":"01","article-title":"Carica papaya Linn: an overview","volume":"2","author":"Yogiraj","year":"2014","journal-title":"Int. J. Herb. Med."},{"key":"2021111619114546300_B21","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1517\/13543784.2015.974804","article-title":"Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease","volume":"24","author":"Esser","year":"2015","journal-title":"Expert Opin. Invest. Drugs"},{"key":"2021111619114546300_B22","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0014-5793(81)80114-7","article-title":"Formation of a thiobarbituric-acid-reactive substance from deoxyribose in the presence of iron salts: the role of superoxide and hydroxyl radicals","volume":"128","author":"Halliwell","year":"1981","journal-title":"FEBS Lett."},{"volume-title":"Phytochemical Methods a Guide to Modern Techniques of Plant Analysis","year":"1998","author":"Harborne","key":"2021111619114546300_B23"},{"key":"2021111619114546300_B24","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/B978-1-4832-2845-7.50012-8","article-title":"Toxicity tests","volume-title":"Evaluation of Drug Activities: Pharmacometrics","author":"Paget","year":"1964"},{"key":"2021111619114546300_B25","first-page":"863","article-title":"Comparative quantitative clinico-chemical analysis of the characteristics of 24-hour urine and morning urine","volume":"24","author":"Krieg","year":"1986","journal-title":"J. Clin. Chem. Clin. Biochem."},{"key":"2021111619114546300_B26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3109\/00365516509077065","article-title":"Plasma creatinine determination a new and specific Jaffe reaction method","volume":"17","author":"Slot","year":"1965","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"2021111619114546300_B27","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"volume-title":"Theory and Practice of Histological Techniques","year":"2008","author":"Bancroft","key":"2021111619114546300_B28"},{"key":"2021111619114546300_B29","doi-asserted-by":"crossref","DOI":"10.14393\/BJ-v33n2-33736","article-title":"Potent anti-oxidant and anti-inflammatory potentials of Punica granatum leaf and flower hydromethanolic extracts in vitro","volume":"33","author":"Gheith","year":"2017","journal-title":"Biosci. J."},{"key":"2021111619114546300_B30","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S1734-1140(12)70728-4","article-title":"Animal models of acute renal failure","volume":"64","author":"Singh","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"2021111619114546300_B31","first-page":"364","article-title":"The changing epidemiology of acute renal failure","volume":"2","author":"Lameire","year":"2006","journal-title":"Nat. Rev."},{"key":"2021111619114546300_B32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.5527\/wjn.v4.i2.160","article-title":"Novel biomarkers of acute kidney injury: evaluation and evidence in urologic surgery","volume":"4","author":"Schmid","year":"2015","journal-title":"World J. Nephrol."},{"key":"2021111619114546300_B33","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1093\/qjmed\/hcp143","article-title":"Gentamicin-associated acute kidney injury","volume":"102","author":"Selby","year":"2009","journal-title":"QJM: Int. J. Med."},{"key":"2021111619114546300_B34","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1128\/AAC.43.5.1003","article-title":"Aminoglycosides: nephrotoxicity","volume":"43","author":"Mingeot-Leclercq","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"2021111619114546300_B35","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1016\/0306-3623(95)00049-6","article-title":"Gentamicin nephrotoxicity in humans and animals: some recent research","volume":"26","author":"Ali","year":"1995","journal-title":"Gen. Pharmacol. Vasc. Sys."},{"key":"2021111619114546300_B36","doi-asserted-by":"publisher","first-page":"124","DOI":"10.5923\/j.als.20120204.08","article-title":"Dose-dependent attenuating effects of aqueous extract of Carica papaya seed on carbontetrachloride-induced renal toxicity in rats","volume":"2","author":"Nwangwa","year":"2012","journal-title":"Adv. Life Sci."},{"key":"2021111619114546300_B37","doi-asserted-by":"publisher","first-page":"598","DOI":"10.4314\/ahs.v15i2.37","article-title":"The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats","volume":"15","author":"Madinah","year":"2015","journal-title":"Afr. Health Sci."},{"key":"2021111619114546300_B38","article-title":"Antioxidant analysis of different parts of Carica papaya","volume":"20","author":"Maisarah","year":"2013","journal-title":"Int. Food Res. J."},{"key":"2021111619114546300_B39","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.bjp.2014.07.012","article-title":"Phytochemical screening and hypoglycemic activity of Carica papaya leaf in streptozotocin-induced diabetic rats","volume":"24","author":"Ju\u00e1rez-Rojop","year":"2014","journal-title":"Rev. Bras. Farmacog."},{"key":"2021111619114546300_B40","first-page":"2250","article-title":"Phytochemical analysis of paw-paw (Carica papaya) leaves","volume":"2","author":"Ikeyi","year":"2013","journal-title":"Int. J. Life Sci. Bt. Pharm. Res."},{"key":"2021111619114546300_B41","first-page":"193","article-title":"Phytochemical screening, antimicrobial and antioxidant properties of assorted Carica papaya leaves in Ghana","volume":"4","author":"Alorkpa","year":"2016","journal-title":"J. Med. Plants"},{"key":"2021111619114546300_B42","first-page":"880","article-title":"Phytochemical studies on Carica papaya leaf juice","volume":"6","author":"Akhila","year":"2015","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"2021111619114546300_B43","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1177\/2156587217691891","article-title":"Ocimum gratissimum ameliorates gentamicin-induced kidney injury but decreases creatinine clearance following sub-chronic administration in rats","volume":"22","author":"Ogundipe","year":"2017","journal-title":"J. Evid. Based Complement. Altern. Med."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20181187\/809349\/bsr-2018-1187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20181187\/809349\/bsr-2018-1187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T02:16:23Z","timestamp":1751854583000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/38\/5\/BSR20181187\/87719\/Novel-and-classical-renal-biomarkers-as-evidence"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,21]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,10,31]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20181187","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"type":"print","value":"0144-8463"},{"type":"electronic","value":"1573-4935"}],"subject":[],"published":{"date-parts":[[2018,9,21]]},"article-number":"BSR20181187"}}