PMID- 31423645 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20200423 IS - 1439-0396 (Electronic) IS - 0931-2439 (Linking) VI - 103 IP - 6 DP - 2019 Nov TI - Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells. PG - 1663-1674 LID - 10.1111/jpn.13180 [doi] AB - Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium graminearum. It is one of the most common feed contaminants that poses a serious threat to the health and performance of dairy cows. This study investigated the in vitro cytotoxicity of DON on bovine mammary epithelial cells (MAC-T). DON at different concentrations (0.25, 0.3, 0.5, 0.8, 1 or 2 mug/ml) inhibited the growth of MAC-T cells after 24 hr of exposure (p < .001). DON at 0.25 mug/ml increased lactate dehydrogenase (LDH) leakage (p < .05); decreased glutathione (GSH) levels (p < .001), total superoxide dismutase (T-SOD) activity and total antioxidant capacity (T-AOC; p < .01); and increased malondialdehyde (MDA) concentration (p < .01) in MAC-T cells after 24 hr of exposure. We also observed that DON increased reactive oxygen species (ROS) levels in cells incubated for 9, 15 and 24 hr (p < .001). DON at 0.25 mug/ml triggered oxidative damage in MAC-T cells. Furthermore, it induced an inflammatory response in the cells incubated for 9, 15 and 24 hr (p < .05) by increasing the mRNA expression levels of nuclear factor kappa B, myeloid differentiation factor 88 (MyD88), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, cyclooxygenase-2 and IL-8. We further examined the effect of DON on apoptosis. DON prevented normal proliferation of MAC-T cells by blocked cell cycle progression in 24 hr (p < .001). In addition, the apoptosis rate measured using annexin V-FITC significantly increased (p < .05) with increase in the mRNA expression level of Bax (p < .01) and increase in the Bax/Bcl-2 ratio (p < .01) in cells incubated for 24 hr. In summary, DON exerts toxic effects in MAC-T cells by causing oxidative stress, inducing an inflammatory response, affecting cell cycle and leading to apoptosis. CI - (c) 2019 The Authors. Journal of Animal Physiology and Animal Nutrition Published by Blackwell Verlag GmbH. FAU - Wang, Junmei AU - Wang J AD - College of Animal Science, Jilin University, Changchun, China. FAU - Jin, Yongcheng AU - Jin Y AD - College of Animal Science, Jilin University, Changchun, China. FAU - Wu, Shunlu AU - Wu S AD - College of Animal Science, Jilin University, Changchun, China. FAU - Yu, Hao AU - Yu H AD - College of Animal Science, Jilin University, Changchun, China. FAU - Zhao, Yun AU - Zhao Y AD - College of Animal Science, Jilin University, Changchun, China. FAU - Fang, Hengtong AU - Fang H AD - College of Animal Science, Jilin University, Changchun, China. FAU - Shen, Jinglin AU - Shen J AD - College of Animal Science, Jilin University, Changchun, China. FAU - Zhou, Changhai AU - Zhou C AD - College of Animal Science, Jilin University, Changchun, China. FAU - Fu, Yurong AU - Fu Y AD - College of Animal Science, Jilin University, Changchun, China. FAU - Li, Ruihua AU - Li R AD - College of Animal Science, Jilin University, Changchun, China. FAU - Wang, Rui AU - Wang R AUID- ORCID: 0000-0003-3454-7082 AD - College of Animal Science, Jilin University, Changchun, China. FAU - Wang, Junxiong AU - Wang J AD - College of Animal Science, Jilin University, Changchun, China. FAU - Zheng, Kexin AU - Zheng K AD - College of Animal Science, Jilin University, Changchun, China. FAU - Fan, Qingsong AU - Fan Q AD - College of Animal Science, Jilin University, Changchun, China. FAU - Chen, Bojiong AU - Chen B AD - College of Animal Science, Jilin University, Changchun, China. FAU - Zhang, Jing AU - Zhang J AUID- ORCID: 0000-0002-4823-4629 AD - College of Animal Science, Jilin University, Changchun, China. LA - eng SI - GENBANK/NM_173979.3 SI - GENBANK/NM_001076409.1 SI - GENBANK/NM_001080242.2 SI - GENBANK/NM_174445.2 SI - GENBANK/NM_173923.2 SI - GENBANK/NM_173925.2 SI - GENBANK/NM_174093.1 SI - GENBANK/NM_001014382.2 SI - GENBANK/NM_173966.3 SI - GENBANK/NM_173894.1 SI - GENBANK/NM_001166486.1 GR - SXGJXX2017-4/the Special Project of the Province-University Co-constructing Program of Jilin Province/ GR - the Jilin Modern Agricultural Technology Demonstration and Extension Project, P.R. China./ GR - 20170307018NY/the Jilin Scientific and Technological Development Program/ GR - 20190301034NY/the Jilin Scientific and Technological Development Program/ PT - Journal Article DEP - 20190818 PL - Germany TA - J Anim Physiol Anim Nutr (Berl) JT - Journal of animal physiology and animal nutrition JID - 101126979 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Annexin A5) RN - 0 (Antioxidants) RN - 0 (FITC-annexin A5) RN - 0 (GluB protein, Corynebacterium glutamicum) RN - 0 (Periplasmic Binding Proteins) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Trichothecenes) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) RN - JT37HYP23V (deoxynivalenol) SB - IM MH - ATP-Binding Cassette Transporters/metabolism MH - Animals MH - Annexin A5/metabolism MH - Antioxidants/metabolism MH - Apoptosis/*drug effects MH - *Cattle MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Survival MH - Epithelial Cells/*drug effects/physiology MH - Female MH - Fluorescein-5-isothiocyanate/analogs & derivatives/metabolism MH - Gene Expression Regulation/drug effects MH - Inflammation/chemically induced/*veterinary MH - Malondialdehyde/metabolism MH - Mammary Glands, Animal MH - Oxidative Stress/*drug effects MH - Periplasmic Binding Proteins/metabolism MH - RNA, Messenger/genetics/metabolism MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism MH - Trichothecenes/*pharmacology OTO - NOTNLM OT - apoptosis OT - bovine mammary epithelial cells OT - deoxynivalenol OT - inflammation OT - oxidative stress EDAT- 2019/08/20 06:00 MHDA- 2020/04/24 06:00 CRDT- 2019/08/20 06:00 PHST- 2019/05/14 00:00 [received] PHST- 2019/07/05 00:00 [revised] PHST- 2019/07/16 00:00 [accepted] PHST- 2019/08/20 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] PHST- 2019/08/20 06:00 [entrez] AID - 10.1111/jpn.13180 [doi] PST - ppublish SO - J Anim Physiol Anim Nutr (Berl). 2019 Nov;103(6):1663-1674. doi: 10.1111/jpn.13180. Epub 2019 Aug 18.