Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy
Hypertension can originate from early-life exposure to oxidative stress. As reported, dimethyl fumarate (DMF) activates nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and protects against oxidative stress damage. We examined whether maternal DMF therapy protects adult offspring against h...
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doaj-c3c914b18e9a4f6398ba7f213b2d04692020-11-25T02:18:33ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-08-012016395710.3390/ijms20163957ijms20163957Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during PregnancyChien-Ning Hsu0Yu-Ju Lin1Hong-Ren Yu2I-Chun Lin3Jiunn-Ming Sheen4Li-Tung Huang5You-Lin Tain6Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanHypertension can originate from early-life exposure to oxidative stress. As reported, dimethyl fumarate (DMF) activates nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and protects against oxidative stress damage. We examined whether maternal DMF therapy protects adult offspring against hypertension programmed by prenatal dexamethasone (DEX) and postnatal high-fat (HF) diet exposure. We examined male Sprague Dawley rat offspring at 4 months of age from five groups (<i>n</i> = 11−13/group): control, DEX (0.1mg/kg i.p. from gestational day 16 to 22), HF (D12331 diet from weaning to 16 weeks of age), DEX+HF, and DEX+HF+DMF (50mg/kg/day via gastric gavage for 3 weeks during pregnancy). Maternal DMF therapy prevented male offspring against hypertension programmed by combined DEX and HF exposures. The protective effects of maternal DMF include reduced oxidative stress, decreased plasma asymmetric dimethylarginine (ADMA) levels, downregulated the renin-angiotensin system (i.e. <i>Ren</i>, <i>Agt</i>, <i>Ace</i>, and <i>Agtr1a</i>), increased renal protein levels of certain nutrient-sensing signals, and promoted autophagy. In conclusion, maternal Nrf2 activation by DMF protects male adult offspring against hypertension programmed by combined DEX and HF exposures. Our results cast a new light on the therapeutic potential of targeting Nrf2 signaling pathway as reprogramming strategies to prevent programmed hypertension in children exposed to antenatal corticosteroids and postnatally excessive consumption of fat.https://www.mdpi.com/1422-0067/20/16/3957asymmetric dimethylargininedevelopmental origins of health and disease (DOHaD)hypertensionnuclear factor erythroid-derived 2-related factor 2 (Nrf2)nitric oxidenutrient sensing signaloxidative stressrenin-angiotensin system |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chien-Ning Hsu Yu-Ju Lin Hong-Ren Yu I-Chun Lin Jiunn-Ming Sheen Li-Tung Huang You-Lin Tain |
spellingShingle |
Chien-Ning Hsu Yu-Ju Lin Hong-Ren Yu I-Chun Lin Jiunn-Ming Sheen Li-Tung Huang You-Lin Tain Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy International Journal of Molecular Sciences asymmetric dimethylarginine developmental origins of health and disease (DOHaD) hypertension nuclear factor erythroid-derived 2-related factor 2 (Nrf2) nitric oxide nutrient sensing signal oxidative stress renin-angiotensin system |
author_facet |
Chien-Ning Hsu Yu-Ju Lin Hong-Ren Yu I-Chun Lin Jiunn-Ming Sheen Li-Tung Huang You-Lin Tain |
author_sort |
Chien-Ning Hsu |
title |
Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy |
title_short |
Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy |
title_full |
Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy |
title_fullStr |
Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy |
title_full_unstemmed |
Protection of Male Rat Offspring against Hypertension Programmed by Prenatal Dexamethasone Administration and Postnatal High-Fat Diet with the Nrf2 Activator Dimethyl Fumarate during Pregnancy |
title_sort |
protection of male rat offspring against hypertension programmed by prenatal dexamethasone administration and postnatal high-fat diet with the nrf2 activator dimethyl fumarate during pregnancy |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-08-01 |
description |
Hypertension can originate from early-life exposure to oxidative stress. As reported, dimethyl fumarate (DMF) activates nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and protects against oxidative stress damage. We examined whether maternal DMF therapy protects adult offspring against hypertension programmed by prenatal dexamethasone (DEX) and postnatal high-fat (HF) diet exposure. We examined male Sprague Dawley rat offspring at 4 months of age from five groups (<i>n</i> = 11−13/group): control, DEX (0.1mg/kg i.p. from gestational day 16 to 22), HF (D12331 diet from weaning to 16 weeks of age), DEX+HF, and DEX+HF+DMF (50mg/kg/day via gastric gavage for 3 weeks during pregnancy). Maternal DMF therapy prevented male offspring against hypertension programmed by combined DEX and HF exposures. The protective effects of maternal DMF include reduced oxidative stress, decreased plasma asymmetric dimethylarginine (ADMA) levels, downregulated the renin-angiotensin system (i.e. <i>Ren</i>, <i>Agt</i>, <i>Ace</i>, and <i>Agtr1a</i>), increased renal protein levels of certain nutrient-sensing signals, and promoted autophagy. In conclusion, maternal Nrf2 activation by DMF protects male adult offspring against hypertension programmed by combined DEX and HF exposures. Our results cast a new light on the therapeutic potential of targeting Nrf2 signaling pathway as reprogramming strategies to prevent programmed hypertension in children exposed to antenatal corticosteroids and postnatally excessive consumption of fat. |
topic |
asymmetric dimethylarginine developmental origins of health and disease (DOHaD) hypertension nuclear factor erythroid-derived 2-related factor 2 (Nrf2) nitric oxide nutrient sensing signal oxidative stress renin-angiotensin system |
url |
https://www.mdpi.com/1422-0067/20/16/3957 |
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