Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy

Growing evidences reveal that Nrf2-mediated antioxidant defense response and mitophagy are involved in the toxic mechanism of heavy metals, but the effects of molybdenum (Mo) and cadmium (Cd) co-exposure on Nrf2-mediated antioxidant defense response and mitophagy in duck hypothalamus have yet to be...

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Autores principales:	Ting Cui, Wenjuan Jiang, Fan Yang, Junrong Luo, Ruiming Hu, Huabin Cao, Guoliang Hu, Caiying Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molybdenum Cadmium Nrf2-mediated antioxidant defense Mitophagy Hypothalamus Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/875b540a80084fd9b2479f738099fc3a
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spelling	oai:doaj.org-article:875b540a80084fd9b2479f738099fc3a2021-11-28T04:27:25ZMolybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy0147-651310.1016/j.ecoenv.2021.113022https://doaj.org/article/875b540a80084fd9b2479f738099fc3a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011349https://doaj.org/toc/0147-6513Growing evidences reveal that Nrf2-mediated antioxidant defense response and mitophagy are involved in the toxic mechanism of heavy metals, but the effects of molybdenum (Mo) and cadmium (Cd) co-exposure on Nrf2-mediated antioxidant defense response and mitophagy in duck hypothalamus have yet to be elucidated. Herein, 40 healthy 7-day-old ducks were randomly assigned to 4 groups and fed diets containing different doses of Mo or/and Cd for 16 weeks, respectively. The data demonstrated that Mo or/and Cd notably elevated their contents in hypothalamus, decreased Cu, Fe, Zn and Se contents, caused pathological damage and oxidative stress accompanied by elevating MDA content and reducing CAT, T-AOC, T-SOD, GSH-Px activities. Moreover, Mo or/and Cd not only restrained Nrf2 pathway by decreasing Nrf2, HO-1, NQO1, GST, CAT, SOD1, GCLM mRNA expression levels and Nrf2 protein expression level, but also disturbed mitochondrial dynamics and triggered PINK1/Parkin-mediated mitophagy by enhancing MFF, PINK1, Parkin, Bnip3, LC3A, LC3B mRNA expression levels and PINK1, Parkin, LC3B-II/LC3B-I protein expression levels, inhibiting Mfn1, Mfn2, OPA1, P62 mRNA expression levels and P62 protein expression level, and facilitating the colocalization between LC3 and HSP60. The changes of above factors were most remarkable under Mo and Cd co-treatment. Overall, the results elucidate that Mo and Cd can synergistically inhibit Nrf2-mediated antioxidant defense response and activate PINK1/Parkin pathway-dependent mitophagy in duck hypothalamus, whose mechanism is somehow related to Mo and Cd accumulation.Ting CuiWenjuan JiangFan YangJunrong LuoRuiming HuHuabin CaoGuoliang HuCaiying ZhangElsevierarticleMolybdenumCadmiumNrf2-mediated antioxidant defenseMitophagyHypothalamusEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 113022- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molybdenum Cadmium Nrf2-mediated antioxidant defense Mitophagy Hypothalamus Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Molybdenum Cadmium Nrf2-mediated antioxidant defense Mitophagy Hypothalamus Environmental pollution TD172-193.5 Environmental sciences GE1-350 Ting Cui Wenjuan Jiang Fan Yang Junrong Luo Ruiming Hu Huabin Cao Guoliang Hu Caiying Zhang Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
description	Growing evidences reveal that Nrf2-mediated antioxidant defense response and mitophagy are involved in the toxic mechanism of heavy metals, but the effects of molybdenum (Mo) and cadmium (Cd) co-exposure on Nrf2-mediated antioxidant defense response and mitophagy in duck hypothalamus have yet to be elucidated. Herein, 40 healthy 7-day-old ducks were randomly assigned to 4 groups and fed diets containing different doses of Mo or/and Cd for 16 weeks, respectively. The data demonstrated that Mo or/and Cd notably elevated their contents in hypothalamus, decreased Cu, Fe, Zn and Se contents, caused pathological damage and oxidative stress accompanied by elevating MDA content and reducing CAT, T-AOC, T-SOD, GSH-Px activities. Moreover, Mo or/and Cd not only restrained Nrf2 pathway by decreasing Nrf2, HO-1, NQO1, GST, CAT, SOD1, GCLM mRNA expression levels and Nrf2 protein expression level, but also disturbed mitochondrial dynamics and triggered PINK1/Parkin-mediated mitophagy by enhancing MFF, PINK1, Parkin, Bnip3, LC3A, LC3B mRNA expression levels and PINK1, Parkin, LC3B-II/LC3B-I protein expression levels, inhibiting Mfn1, Mfn2, OPA1, P62 mRNA expression levels and P62 protein expression level, and facilitating the colocalization between LC3 and HSP60. The changes of above factors were most remarkable under Mo and Cd co-treatment. Overall, the results elucidate that Mo and Cd can synergistically inhibit Nrf2-mediated antioxidant defense response and activate PINK1/Parkin pathway-dependent mitophagy in duck hypothalamus, whose mechanism is somehow related to Mo and Cd accumulation.
format	article
author	Ting Cui Wenjuan Jiang Fan Yang Junrong Luo Ruiming Hu Huabin Cao Guoliang Hu Caiying Zhang
author_facet	Ting Cui Wenjuan Jiang Fan Yang Junrong Luo Ruiming Hu Huabin Cao Guoliang Hu Caiying Zhang
author_sort	Ting Cui
title	Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
title_short	Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
title_full	Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
title_fullStr	Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
title_full_unstemmed	Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy
title_sort	molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing nrf2-mediated defense response and triggering mitophagy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/875b540a80084fd9b2479f738099fc3a
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Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy

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