{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:18:07Z","timestamp":1783099087901,"version":"3.54.6"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1603706"],"award-info":[{"award-number":["2018YFC1603706"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than one type of food contaminant by consumers may take place, which provides a strong rationale for investigating the combined toxicities of these food contaminants. Patulin is one of the most common food-borne mycotoxins, whereas cadmium is a representative of toxic heavy metals found in food. The liver and kidneys are the main target organ sites for both patulin and cadmium. We hypothesized that simultaneous exposure to patulin and cadmium could produce synergistic hepatotoxicity and nephrotoxicity. Alpha mouse liver 12 (AML12) and Human embryonic kidney (HEK) 293 (HEK293) cell lines together with a mouse model were used to explore the combination effect and mechanism. The results demonstrated, for the first time, that the co-exposure of liver or renal cells to patulin and cadmium caused synergistic cytotoxicity in vitro and enhanced liver toxicity in vivo. The synergistic toxicity caused by the co-administration of patulin and cadmium was attributed to the boosted reactive oxygen species (ROS) generation. c-Jun N-terminal kinase 1 (JNK1) and p53 as downstream mediators of oxidative stress contributed to the synergistic toxicity by co-exposure of patulin and cadmium, while p53\/JNK1 activation promoted the second-round ROS production through a positive feedback loop. The findings of the present study extend the toxicological knowledge about patulin and cadmium, which could be beneficial to more precisely perform risk assessments on these food contaminants.<\/jats:p>","DOI":"10.3390\/toxins13030221","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T22:19:36Z","timestamp":1616105976000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Combining Patulin with Cadmium Induces Enhanced Hepatotoxicity and Nephrotoxicity In Vitro and In Vivo"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-6756","authenticated-orcid":false,"given":"Jinling","family":"Cui","sequence":"first","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-Thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-7370","authenticated-orcid":false,"given":"Shutao","family":"Yin","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-Thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-Thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, No.2 Yunamingyuan West Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, Beijing Key Laboratory for Food Non-Thermal Processing, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3390\/toxins2040613","article-title":"Biosynthesis and Toxicological Effects of Patulin","volume":"2","author":"Puel","year":"2010","journal-title":"Toxins"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1039\/c7tx00138j","article-title":"Toxicological effects of patulin mycotoxin on the mammalian system: An overview","volume":"6","author":"Pal","year":"2017","journal-title":"Toxicol. 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