{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:38:50Z","timestamp":1791664730383,"version":"4.3.4"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education, Research and Innovation","award":["RC\/MED\/PHAR\/19\/01"],"award-info":[{"award-number":["RC\/MED\/PHAR\/19\/01"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine\u2013induced CKD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin\/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1\u03b2 and 6, and NF-\u03baB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0258800","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T22:19:20Z","timestamp":1634854760000},"page":"e0258800","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of flaxseed on systemic inflammation and oxidative stress in diabetic rats with or without chronic kidney disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-1022","authenticated-orcid":true,"given":"Mohammed","family":"Al Za\u2019abi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haytham","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badreldin H.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"pone.0258800.ref001","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"AS Go","year":"2004","journal-title":"N Engl J Med"},{"key":"pone.0258800.ref002","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"395","author":"GBD Chronic Kidney Disease Collaboration","year":"2020","journal-title":"Lancet"},{"key":"pone.0258800.ref003","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ki.2015.230","article-title":"A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010","volume":"88","author":"KT Mills","year":"2015","journal-title":"Kidney Int"},{"key":"pone.0258800.ref004","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.kisu.2017.07.007","article-title":"Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action","volume":"7","author":"AK Bello","year":"2017","journal-title":"Kidney Int Suppl (2011)."},{"key":"pone.0258800.ref005","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"P Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"pone.0258800.ref006","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00038-017-1014-1","article-title":"Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study","volume":"63","author":"GBD 2015 Eastern Mediterranean Region Diabetes and Chronic Kidney Disease Collaborators","year":"2018","journal-title":"Int J Public Health"},{"key":"pone.0258800.ref007","doi-asserted-by":"crossref","first-page":"3086167","DOI":"10.1155\/2018\/3086167","article-title":"Complications of Diabetes 2017","volume":"2018","author":"K Papatheodorou","year":"2018","journal-title":"J Diabetes Res."},{"key":"pone.0258800.ref008","unstructured":"Centers for Disease Control and Prevention. Chronic diseases in the United States, 2019 website. https:\/\/www.cdc.gov\/kidneydisease. Accessed June, 2020."},{"key":"pone.0258800.ref009","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000368940","article-title":"Update on Inflammation in Chronic Kidney Disease","volume":"39","author":"OM Akchurin","year":"2015","journal-title":"Blood Purif"},{"key":"pone.0258800.ref010","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","article-title":"The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives","volume":"14","author":"S Tsalamandris","year":"2019","journal-title":"Eur Cardiol"},{"key":"pone.0258800.ref011","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.2337\/diabetes.52.7.1799","article-title":"Atherosclerosis risk in communities study. Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study","volume":"52","author":"BB Duncan","year":"2003","journal-title":"Diabetes"},{"key":"pone.0258800.ref012","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000479257","article-title":"Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease","volume":"191","author":"Q. Qian","year":"2017","journal-title":"Contrib Nephrol"},{"key":"pone.0258800.ref013","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s13197-014-1293-y","article-title":"Flaxseed-a potential functional food source","volume":"52","author":"P Kajla","year":"2015","journal-title":"J Food Sci Technol"},{"key":"pone.0258800.ref014","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3390\/nu11051171","article-title":"Dietary Flaxseed as a strategy for improving human health.","volume":"11","author":"M Parikh","year":"2019","journal-title":"Nutrients"},{"key":"pone.0258800.ref015","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/pca.973","article-title":"Microwave-assisted extraction of the main phenolic compounds in flaxseed","volume":"18","author":"V Beejmohun","year":"2007","journal-title":"Phytochem Anal"},{"key":"pone.0258800.ref016","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1541-4337.2009.00105.x","article-title":"Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and Health Benefits","volume":"9","author":"A Tour\u00e9","year":"2010","journal-title":"Compr Rev Food Sci Food Saf"},{"key":"pone.0258800.ref017","doi-asserted-by":"crossref","first-page":"E1181","DOI":"10.3390\/nu10091181","article-title":"Comparative Effects of Native and Defatted Flaxseeds on Intestinal Enzyme Activity and Lipid Metabolism in Rats Fed a High-Fat Diet Containing Cholic Acid","volume":"10","author":"PM Opyd","year":"2018","journal-title":"Nutrients"},{"key":"pone.0258800.ref018","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3109\/0886022X.2015.1136895","article-title":"Flax lignan concentrate reverses alterations in blood pressure, left ventricular functions, lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats.","volume":"38","author":"SH Sawant","year":"2016","journal-title":"Ren Fail"},{"key":"pone.0258800.ref019","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s11745-002-1001-4","article-title":"Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n-6\/n-3 FA ratio in experimental polycystic kidney disease","volume":"37","author":"MR Ogborn","year":"2002","journal-title":"Lipids"},{"key":"pone.0258800.ref020","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.nutres.2012.08.007","article-title":"Flaxseed oil supplementation decreases C-reactive protein levels in chronic hemodialysis patients","volume":"32","author":"JR Lemos","year":"2012","journal-title":"Nutr Res"},{"key":"pone.0258800.ref021","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1016\/j.fct.2010.05.079","article-title":"Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats","volume":"48","author":"M Makni","year":"2010","journal-title":"Food Chem Toxicol"},{"key":"pone.0258800.ref022","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.vascn.2018.04.003","article-title":"Short-term oral gavage administration of adenine induces a model of fibrotic kidney disease in rats","volume":"94","author":"CZ Zhu","year":"2018","journal-title":"J Pharmacol Toxicol Methods"},{"key":"pone.0258800.ref023","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0272-6386(95)90015-2","article-title":"Effects of flaxseed and flax oil diets in a rat-5\/6 renal ablation model","volume":"25","author":"AJ Ingram","year":"1995","journal-title":"Am J Kidney Dis"},{"key":"pone.0258800.ref024","doi-asserted-by":"crossref","first-page":"110761","DOI":"10.1016\/j.biopha.2020.110761","article-title":"Effect of concomitant treatment of curcumin and melatonin on cisplatin-induced nephrotoxicity in rats","volume":"131","author":"BH Ali","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"pone.0258800.ref025","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00210-020-01976-1","article-title":"Effects of repeated increasing doses of cisplatin as models of acute kidney injury and chronic kidney disease in rats","volume":"394","author":"M Al Za\u2019abi","year":"2021","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"pone.0258800.ref026","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1089\/ten.tea.2011.0023","article-title":"Extracellular matrix powder protects against bleomycin-induced pulmonary fibrosis","volume":"17","author":"ML Manni","year":"2011","journal-title":"Tissue Eng Part A"},{"key":"pone.0258800.ref027","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4239\/wjd.v8.i4.120","article-title":"Type 2 diabetes and quality of life","volume":"8","author":"A Trikkalinou","year":"2017","journal-title":"World J Diabetes"},{"key":"pone.0258800.ref028","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1159\/000488176","article-title":"Gum Acacia Improves Renal Function and Ameliorates Systemic Inflammation, Oxidative and Nitrosative Stress in Streptozotocin-Induced Diabetes in Rats with Adenine-Induced Chronic Kidney Disease","volume":"45","author":"M Al Za\u2019abi","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"pone.0258800.ref029","doi-asserted-by":"crossref","first-page":"172960","DOI":"10.1016\/j.ejphar.2020.172960","article-title":"Effect of levosimendan, an inodilator, on streptozotocin-induced diabetic nephropathy in rats","volume":"873","author":"AM Abdelrahman","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"pone.0258800.ref030","first-page":"28","article-title":"Development of a new model for the induction of chronic kidney disease via intraperitoneal adenine administration, and the effect of treatment with gum acacia thereon","volume":"7","author":"M Al Za\u2019abi","year":"2015","journal-title":"Am J Transl Res"},{"key":"pone.0258800.ref031","doi-asserted-by":"crossref","first-page":"e0192531","DOI":"10.1371\/journal.pone.0192531","article-title":"A novel approach to adenine-induced chronic kidney disease associated anemia in rodents","volume":"13","author":"A Rahman","year":"2018","journal-title":"PLoS One"},{"key":"pone.0258800.ref032","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1177\/0960327115571765","article-title":"Flaxseed oil reduces oxidative stress and enhances brain monoamines release in streptozotocin-induced diabetic rats","volume":"34","author":"EA Badawy","year":"2015","journal-title":"Hum Exp Toxicol"},{"key":"pone.0258800.ref033","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.intimp.2016.04.043","article-title":"Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms","volume":"38","author":"AH Palla","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"pone.0258800.ref034","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/bcpt.12817","article-title":"Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease","volume":"122","author":"BH Ali","year":"2018","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"pone.0258800.ref035","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1159\/000438626","article-title":"Therapeutic Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats","volume":"38","author":"BH Ali","year":"2016","journal-title":"Cell Physiol Biochem"},{"key":"pone.0258800.ref036","doi-asserted-by":"crossref","first-page":"61","DOI":"10.33549\/physiolres.934142","article-title":"Ameliorative effect of sesamin in cisplatin-induced nephrotoxicity in rats by suppressing inflammation, oxidative\/nitrosative stress, and cellular damage","volume":"69","author":"BH Ali","year":"2020","journal-title":"Physiol Res."},{"key":"pone.0258800.ref037","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/advances\/nmz048","article-title":"Effects of Flaxseed Interventions on Circulating Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"10","author":"M Rahimlou","year":"2019","journal-title":"Adv Nutr."},{"key":"pone.0258800.ref038","doi-asserted-by":"crossref","first-page":"758","DOI":"10.3945\/jn.114.205302","article-title":"Flaxseed consumption may reduce blood pressure: a systematic review and meta-analysis of controlled trials","volume":"145","author":"S Khalesi","year":"2015","journal-title":"J Nutr"},{"key":"pone.0258800.ref039","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s11357-012-9402-1","article-title":"The interactions of oxidative stress and inflammation with vascular dysfunction in ageing: the vascular health triad","volume":"35","author":"AJ Wadley","year":"2013","journal-title":"Age (Dordr)"},{"key":"pone.0258800.ref040","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"M Mittal","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"pone.0258800.ref041","doi-asserted-by":"crossref","first-page":"L255","DOI":"10.1152\/ajplung.00138.2007","article-title":"Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury","volume":"294","author":"JC Lee","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0258800.ref042","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3390\/nu2030355","article-title":"Omega-3 fatty acids and inflammatory processes","volume":"2","author":"PC Calder","year":"2010","journal-title":"Nutrients"},{"key":"pone.0258800.ref043","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.4238\/2014.July.24.11","article-title":"Flaxseed oil supplementation alters the expression of inflammatory-related genes in dogs","volume":"13","author":"D Purushothaman","year":"2014","journal-title":"Genet Mol Res"},{"key":"pone.0258800.ref044","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13048-019-0523-3","article-title":"Pro-apoptotic and anti-angiogenic actions of 2-methoxyestradiol and docosahexaenoic acid, the biologically derived active compounds from flaxseed diet, in preventing ovarian cancer","volume":"12","author":"P Pal","year":"2019","journal-title":"J Ovarian Res"},{"key":"pone.0258800.ref045","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1021\/jf0702693","article-title":"Anti-inflammatory effect of alpha-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kappa B and mitogen-activated protein kinase pathways","volume":"55","author":"J Ren","year":"2007","journal-title":"J Agric Food Chem"},{"key":"pone.0258800.ref046","doi-asserted-by":"crossref","first-page":"L84","DOI":"10.1152\/ajplung.00077.2002","article-title":"NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription","volume":"284","author":"TE Novak","year":"2003","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0258800.ref047","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"M Saraiva","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"pone.0258800.ref048","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and functions of the IL-10 family of cytokines in inflammation and disease","volume":"29","author":"W Ouyang","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"pone.0258800.ref049","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s12906-015-0651-2","article-title":"Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic fibrosis: a pilot study","volume":"15","author":"JB Turowski","year":"2015","journal-title":"BMC Complement Altern Med"},{"key":"pone.0258800.ref050","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ctim.2019.07.012","article-title":"Effects of flaxseed and flaxseed oil supplement on serum levels of inflammatory markers, metabolic parameters and severity of disease in patients with ulcerative colitis","volume":"46","author":"N Morshedzadeh","year":"2019","journal-title":"Complement Ther Med"},{"key":"pone.0258800.ref051","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1111\/1750-3841.13964","article-title":"Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome","volume":"82","author":"B Pilar","year":"2017","journal-title":"J Food Sci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258800","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T22:20:03Z","timestamp":1634854803000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258800"}},"subtitle":[],"editor":[{"given":"Luis Eduardo M.","family":"Quintas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,19]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258800","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,19]]}}}