{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:15:28Z","timestamp":1790795728250,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010042","name":"Special Fund for Agro-scientific Research in the public Interest","doi-asserted-by":"publisher","award":["201403071"],"award-info":[{"award-number":["201403071"]}],"id":[{"id":"10.13039\/501100010042","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Ministry of Modern Agro-Industry Technology Research System of China","award":["CARS-36"],"award-info":[{"award-number":["CARS-36"]}]},{"name":"the Agricultural Science and Technology Innovation Program","award":["ASTIP-IAS12"],"award-info":[{"award-number":["ASTIP-IAS12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The toxicity and related mechanisms of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the mouse kidney were studied, and the role of l-proline in alleviating kidney damage was investigated. In a 28-day toxicity mouse model, thirty mice were divided into six groups: control (without treatment), l-proline group (10 g\/kg body weight (b.w.)), AFB1 group (0.5 mg\/kg b.w.), AFM1 (3.5 mg\/kg b.w.), AFB1 + l-proline group and AFM1 + l-proline group. Kidney index and biochemical indicators were detected, and pathological staining was observed. Using a human embryonic kidney 293 (HEK 293) cell model, cell apoptosis rate and apoptotic proteins expressions were detected. The results showed that AFB1 and AFM1 activated pathways related with oxidative stress and caused kidney injury; l-proline significantly alleviated abnormal expressions of biochemical parameters and pathological kidney damage, as well as excessive cell apoptosis in the AF-treated models. Moreover, proline dehydrogenase (PRODH) was verified to regulate the levels of l-proline and downstream apoptotic factors (Bax, Bcl-2, and cleaved Caspase-3) compared with the control (p &lt; 0.05). In conclusion, l-proline could protect mouse kidneys from AFB1 and AFM1 through alleviating oxidative damage and decreasing downstream apoptosis, which deserves further research and development.<\/jats:p>","DOI":"10.3390\/toxins11040226","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T03:02:01Z","timestamp":1555470121000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["l-Proline Alleviates Kidney Injury Caused by AFB1 and AFM1 through Regulating Excessive Apoptosis of Kidney Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Huiying","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songli","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaigu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Quality &amp; Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.3168\/jds.S0022-0302(05)72987-8","article-title":"Transfer of aflatoxin B1 from feed to milk and from milk to curd and whey in dairy sheep fed artificially contaminated concentrates","volume":"88","author":"Battacone","year":"2005","journal-title":"J. Dairy Sci."},{"key":"ref_2","unstructured":"Ronchi, B., Danieli, P., Vitali, A., Sabatini, A., Bernabucci, U., and Nardone, A. (2005). Evaluation of AFB1\/AFM1 carry-over in lactating goats exposed to different levels of AFB1 contamination. Book of Abstracts of the 56th Annual Meeting of the European Association for Animal Production, Uppsala, Sweden, European Association for Animal Production."},{"key":"ref_3","first-page":"59","article-title":"Liquid chromatographic method for aflatoxin M1 in milk","volume":"157","author":"Dragacci","year":"2001","journal-title":"Methods Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.canlet.2005.11.018","article-title":"Aflatoxin B1-induced DNA damage and its repair","volume":"241","author":"Bedard","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3390\/ijerph7010178","article-title":"Aflatoxin contamination in food and body fluids in relation to malnutrition and cancer status in Cameroon","volume":"7","author":"Tchana","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_6","first-page":"585","article-title":"Toxicity and biochemical and fine structural effects of synthetic aflatoxins M 1 and B 1 in rat liver","volume":"47","author":"Pong","year":"1971","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1080\/02652030500307115","article-title":"Immunoaffinity clean-up and direct fluorescence measurement of aflatoxins B1 and M1 in pig liver: Comparison with high-performance liquid chromatography determination","volume":"22","author":"Chiavaro","year":"2005","journal-title":"Food Addit. Contam."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"650","DOI":"10.3389\/fphar.2017.00650","article-title":"Development of a UPLC-FLD Method for Detection of Aflatoxin B1 and M1 in Animal Tissue to Study the Effect of Curcumin on Mycotoxin Clearance Rates","volume":"8","author":"Cui","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0278-6915(84)90050-4","article-title":"Aflatoxin exposures in the industrial setting: An epidemiological study of mortality","volume":"22","author":"Hayes","year":"1984","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1006\/taap.1997.8117","article-title":"Aflatoxin B1 activation in human lung","volume":"144","author":"Kelly","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/BF00403368","article-title":"Evidence of aflatoxin B1 in two cases of lung cancer in man","volume":"100","author":"Dvorackova","year":"1981","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_12","first-page":"143","article-title":"Panax ginseng CA Meyer extract counteracts the oxidative stress in rats fed multi-mycotoxins-contaminated diet","volume":"3","author":"Ibrahim","year":"2012","journal-title":"Comun. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.fct.2007.08.034","article-title":"Urinary biomarkers of aflatoxin exposure in young children from Egypt and Guinea","volume":"46","author":"Polychronaki","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/ije\/dym122","article-title":"Aflatoxin exposure in utero causes growth faltering in Gambian infants","volume":"36","author":"Turner","year":"2007","journal-title":"Int. J. Epidemiol."},{"key":"ref_15","first-page":"9074861","article-title":"The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating l-Proline and Downstream Apoptosis","volume":"2018","author":"Li","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/toxsci\/kfv259","article-title":"Aflatoxin B1 Induced Compositional Changes in Gut Microbial Communities of Male F344 Rats","volume":"150","author":"Wang","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22597","DOI":"10.1038\/srep22597","article-title":"Akt mediated phosphorylation of LARP6; critical step in biosynthesis of type I collagen","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1042\/BJ20111627","article-title":"p53 Ser15 phosphorylation disrupts the p53-RPA70 complex and induces RPA70-mediated DNA repair in hypoxia","volume":"443","author":"Madan","year":"2012","journal-title":"Biochem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/02652039509374331","article-title":"Aflatoxins B1, M1 and aflatoxicol in tissues and urine of calves receiving aflatoxin","volume":"12","author":"Sabino","year":"1995","journal-title":"Food Addit. Contam."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.amjmed.2010.02.026","article-title":"Early creatinine shifts predict contrast-induced nephropathy and persistent renal damage after angiography","volume":"123","author":"Ribichini","year":"2010","journal-title":"Am. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ijheh.2006.02.002","article-title":"Determinants of aflatoxin levels in Ghanaians: Sociodemographic factors, knowledge of aflatoxin and food handling and consumption practices","volume":"209","author":"Jolly","year":"2006","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/0748233709103413","article-title":"The antioxidant effects of vitamin A, C, and E on aflatoxin B1-induced oxidative stress in human lymphocytes","volume":"25","author":"Alpsoy","year":"2009","journal-title":"Toxicol. Ind. Health"},{"key":"ref_23","first-page":"422","article-title":"The significance of Cys-C UREA and Scr tests in early renal damage assessment of acute glomerulonephritis","volume":"4","author":"Wang","year":"2017","journal-title":"Labeled Immunoass. Clin. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/CS20080039","article-title":"Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats","volume":"116","author":"Olearczyk","year":"2009","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_25","first-page":"237","article-title":"Correlation of serum uric acid and early renal damage in patients with type 2 diabetes mellitus","volume":"27","author":"Liu","year":"2012","journal-title":"Anhui Med. Pharm. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3346\/jkms.2005.20.5.841","article-title":"Comparison of renal damage by iodinated contrast or gadolinium in an acute renal failure rat model based on serum creatinine levels and apoptosis degree","volume":"20","author":"Kwak","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_27","unstructured":"Liu, S.X., Li, C.G., and Dai, D.L. (2010). Effect of ligustrazine on MDA, SOD and T-AOC in erythrocyte membrane in patients with hemoglobin H disease. J. Clin. Exp. Med., 11."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/S0891-5849(02)00821-3","article-title":"Substitution of isoleucine-31 by helical-breaking proline abolishes oxidative stress and neurotoxic properties of Alzheimer\u2019s amyloid beta-peptide","volume":"32","author":"Kanski","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","first-page":"269","article-title":"The effect of various pulse amplitudes on the amount of SOD, MDA, and T-AOC in the diaphagm of rabbit atter diaphragm pacing","volume":"26","author":"Xiang","year":"2004","journal-title":"Chinese J. Phys. Med. Rehabil."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Son, Y.O., Hitron, J.A., and Shi, X. (2013). Chromium (VI), Oxidative Cell Damage, Springer.","DOI":"10.1007\/978-1-4614-1533-6_6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00425-004-1237-2","article-title":"Relationship between copper- and zinc-induced oxidative stress and proline accumulation in Scenedesmus sp.","volume":"219","author":"Tripathi","year":"2004","journal-title":"Planta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jplph.2014.09.011","article-title":"Selenium and sulfur influence ethylene formation and alleviate cadmium-induced oxidative stress by improving proline and glutathione production in wheat","volume":"173","author":"Khan","year":"2015","journal-title":"J. Plant. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1128\/AEM.02428-05","article-title":"Tomato QM-like protein protects Saccharomyces cerevisiae cells against oxidative stress by regulating intracellular proline levels","volume":"72","author":"Chen","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.freeradbiomed.2007.10.054","article-title":"Proline modulates the intracellular redox environment and protects mammalian cells against oxidative stress","volume":"44","author":"Krishnan","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10725-006-9121-7","article-title":"Salinity-induced changes in two cultivars of Vigna radiata: Responses of antioxidative and proline metabolism","volume":"50","author":"Sumithra","year":"2006","journal-title":"J. Plant Growth Regul."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1128\/JB.02282-14","article-title":"Proline metabolism increases katG expression and oxidative stress resistance in Escherichia coli","volume":"197","author":"Zhang","year":"2015","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1073\/pnas.0906101107","article-title":"Crystal structure of the bifunctional proline utilization A flavoenzyme from Bradyrhizobium japonicum","volume":"107","author":"Srivastava","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:45:50Z","timestamp":1760186750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,16]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["toxins11040226"],"URL":"https:\/\/doi.org\/10.3390\/toxins11040226","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,16]]}}}