{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:17:25Z","timestamp":1790770645169,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Jazan University","award":["FS10-042"],"award-info":[{"award-number":["FS10-042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg\/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1\u03b2 and TNF\u03b1) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.<\/jats:p>","DOI":"10.3390\/ijms231911615","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-219X","authenticated-orcid":false,"given":"Saeed","family":"Alshahrani","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani M.","family":"Ali Thubab","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman M.","family":"Ali Zaeri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarique","family":"Anwer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-1264","authenticated-orcid":false,"given":"Rayan A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-2385","authenticated-orcid":false,"given":"Abdulmajeed M.","family":"Jali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Qadri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousra","family":"Nomier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-0166","authenticated-orcid":false,"given":"Sivakumar S.","family":"Moni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-8658","authenticated-orcid":false,"given":"Mohammad F.","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/ckj\/sft135","article-title":"Nephrotoxicity of recent anti-cancer agents","volume":"7","author":"Lameire","year":"2014","journal-title":"Clin. Kidney J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1385\/MO:21:2:167","article-title":"Cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or meta-static adrenocortical cancer","volume":"21","author":"Khan","year":"2004","journal-title":"Med. Oncol."},{"key":"ref_3","first-page":"3016","article-title":"Comparison of the mutagenicity and teratogenicity of cyclophosphamide and its active metabolites, 4-hydroxycyclophosphamide, phosphoramide mustard, and acrolein","volume":"42","author":"Hales","year":"1982","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/BF00254056","article-title":"Metabolism of high doses of cyclophosphamide","volume":"8","author":"Milsted","year":"1982","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0140-6736(94)92211-X","article-title":"Free radicals, antioxidants, and human disease curiosity, cause, or consequence?","volume":"344","author":"Barry","year":"1994","journal-title":"Lancet"},{"key":"ref_6","first-page":"794","article-title":"Free radicals and antioxidants in human health, Current status and future prospects","volume":"52","author":"Devasagayam","year":"2004","journal-title":"J. Assoc. Phys. India"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1046\/j.1365-2141.2001.02595.x","article-title":"The superoxide dismutase content in erythrocytes predicts short-term toxicity of high-dose cyclophosphamide","volume":"112","author":"Dumontet","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2016.6665","article-title":"Oxidant mechanisms in renal injury and disease","volume":"25","author":"Ratliff","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","first-page":"4","article-title":"Myeloprotective activity of crude methanolic leaf extract of Cassia occidentalis in cyclophosphamideinduced bone marrow suppression in Wistar rats","volume":"6","author":"Neboh","year":"2015","journal-title":"Adv. Biomed. Res."},{"key":"ref_10","unstructured":"Khan, M.S.A., Ahmad, I., and Chattopadhyay, D. (2019). Chapter 1\u2014Herbal Medicine: Current Trends and Future Prospects. New Look to Phytomedicine, Academic Press."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.36953\/ECJ.2020.211203","article-title":"Chemical characterization and antibacterial efficacy of Saudi sesame oil against human pathogenic bacteria","volume":"21","author":"Alshahrani","year":"2020","journal-title":"Environ. Conserv. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1159\/000486026","article-title":"Sesamin protects against cardiac remodeling via Sirt3\/ROS Pathway","volume":"44","author":"Fan","year":"2020","journal-title":"Cell Physiol. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1039\/C7FO00204A","article-title":"Sesamin prevents apoptosis and inflammation after experimental myocardial infarction by JNK and NF-\u03baB pathways","volume":"8","author":"Fan","year":"2017","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1113\/EP085251","article-title":"Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice high-fat diet-induced diabetes","volume":"100","author":"Takada","year":"2015","journal-title":"Exp. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00394-006-0617-8","article-title":"Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor-deficient mice","volume":"45","author":"Penalvo","year":"2006","journal-title":"Eur. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1248\/bpb.18.1283","article-title":"Antihypertensive effect of sesamin. II. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy","volume":"18","author":"Kita","year":"1995","journal-title":"Biol. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000177771","article-title":"Protective effects of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents","volume":"37","author":"Akimoto","year":"1993","journal-title":"Ann. Nutr. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3892\/mmr.2015.4546","article-title":"Sesamin attenuates mast cell-mediated allergic responses by suppressing the activation of p38 and nuclear factor-\u03baB","volume":"13","author":"Li","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.33549\/physiolres.934142","article-title":"Ameliorative effect of sesamin in cispla-tin-induced nephrotoxicity in rats by suppressing inflammation, oxidative\/nitrosative stress, and cellular damage","volume":"69","author":"Ali","year":"2020","journal-title":"Physiol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.urology.2012.06.053","article-title":"The Protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats","volume":"80","author":"Sinanoglu","year":"2012","journal-title":"Urology"},{"key":"ref_21","first-page":"337","article-title":"Nephrotoxicity of anticancer drugs\u2014An underestimated problem","volume":"66","author":"Lameire","year":"2011","journal-title":"Acta Clin. Belg."},{"key":"ref_22","first-page":"555","article-title":"Mid-life African-American women with type 2 diabetes, influence on work and the multicare giver role","volume":"12","author":"Cagle","year":"2002","journal-title":"Ethn. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/hmg\/ddg046","article-title":"Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington\u2019s disease knock-in mice","volume":"12","author":"Gines","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1096\/fj.11-196543","article-title":"Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer","volume":"26","author":"Rehman","year":"2012","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1208\/s12248-011-9301-x","article-title":"Biomarkers for drug-induced renal damage and nephrotoxicity-an overview for applied toxicology","volume":"13","author":"Fuchs","year":"2011","journal-title":"AAPS J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ebrahimi, B., Eirin, A., Li, Z., Zhu, X., Zhang, X., Lerman, A., Textor, S.C., and Lerman, L.O. (2013). Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067474"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/jnci\/84.22.1744","article-title":"Individual variation in the activation and inactivation of metabolic pathways of cyclophosphamide","volume":"84","author":"Boddy","year":"1992","journal-title":"J. Nat. Cancer Inst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0041-008X(84)90313-2","article-title":"Role of acrolein in cyclophosphamide teratogenicity in rat embryos in vitro","volume":"72","author":"Mirkes","year":"1984","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.cbi.2006.02.004","article-title":"Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats","volume":"160","author":"Senthilkumar","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"190","DOI":"10.5306\/wjco.v11.i4.190","article-title":"Nephrotoxicity in cancer treatment, An overview","volume":"11","author":"Santos","year":"2020","journal-title":"World J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1191\/0960327103ht388oa","article-title":"Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide induced biochemical toxicity","volume":"22","author":"Haque","year":"2003","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1023\/B:CBTO.0000013342.17370.16","article-title":"Prophylactic action of melatonin against cyclophosphamide induced oxidative stress in mice","volume":"19","author":"Manda","year":"2003","journal-title":"Cell Biol. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1002\/jsfa.7035","article-title":"The relationship of antioxidant components and antioxidant activity of sesame seed oil","volume":"95","author":"Wan","year":"2015","journal-title":"J. Sci. Food Agric."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.3390\/nu6051931","article-title":"Antinociceptive and anti-inflammatory activities of the sesame oil and sesamin","volume":"6","author":"Monteiro","year":"2014","journal-title":"Nutrients"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"465","DOI":"10.3109\/08923973.2015.1085064","article-title":"Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats","volume":"37","author":"Chen","year":"2015","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/biof.552210139","article-title":"Antioxidative roles of sesamin, a functional lignan in sesame seed, and it\u2019s effect on lipid- and alcohol-metabolism in the liver: A DNA microarray study","volume":"21","author":"Kiso","year":"2004","journal-title":"Biofactors"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1248\/yakushi.17-00191-4","article-title":"Metabolism of Sesamin and Drug-Sesamin Interaction","volume":"138","author":"Sakaki","year":"2018","journal-title":"Yakugaku Zasshi"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.toxlet.2014.06.021","article-title":"Acrolein induced both pulmonary inflammation and the death of lung epithelial cells","volume":"229","author":"Sun","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cbi.2004.10.004","article-title":"Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury","volume":"151","author":"Mythili","year":"2004","journal-title":"Chem. Biol. Interact."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.biopha.2017.05.103","article-title":"Lutein mitigates cyclophosphamide induced lung and liver injury via NF-\u03baB\/MAPK dependent mechanism","volume":"92","author":"Elkablawy","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00109-004-0555-y","article-title":"Nuclear factor-\u03baB, its role in health and disease","volume":"82","author":"Kumar","year":"2004","journal-title":"J. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Alhoshani, A.R., Hafez, M.M., Husain, S., Al-sheikh, A.M., Alotaibi, M.R., Al Rejaie, S.S., Alshammari, M.A., Almutairi, M.M., and Al-Shabanah, O.A. (2017). Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0601-y"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/cdd.2011.96","article-title":"Molecular definitions of cell death subroutines, recommendations of the Nomenclature Committee on Cell Death 2012","volume":"19","author":"Galluzzi","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00210-019-01741-z","article-title":"Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis","volume":"393","author":"Temel","year":"2020","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cbi.2015.02.021","article-title":"Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats, role of NF\u03baB\/MAPK pathway","volume":"231","author":"Nafees","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/j.biopha.2016.10.097","article-title":"Paeoniflorin ameliorates renal function in cyclophosphamide-induced mice via AMPK suppressed inflammation and apoptosis","volume":"84","author":"Liu","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_47","first-page":"5733","article-title":"Sesamin ameliorates oxidative liver injury induced by carbon tetrachloride in rat","volume":"8","author":"Lv","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1177\/0960327110376552","article-title":"The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats","volume":"30","author":"Abraham","year":"2011","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","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."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_51","first-page":"283","article-title":"Catalase activity","volume":"Volume 1","author":"Claiborne","year":"1985","journal-title":"CRC Handbook of Methods for Oxygen Radical Research"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.2337\/diabetes.49.6.1006","article-title":"Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism and oxidative, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy","volume":"49","author":"Stevens","year":"2000","journal-title":"Diabetes"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11615\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:01Z","timestamp":1760143501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":52,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911615"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911615","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}