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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.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Aug 14; Vol. 20 (16). Date of Electronic Publication: 2019 Aug 14. - Publication Year :
- 2019
-
Abstract
- 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 ( n = 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. Ren , Agt , Ace , and Agtr1a ), 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.
- Subjects :
- Animals
Biomarkers
Female
Gene Expression
Humans
Hypertension diagnosis
Hypertension metabolism
Infant, Newborn
Male
NF-E2-Related Factor 2 genetics
Oxidative Stress
Phosphorylation
Pregnancy
Rats
Dexamethasone administration & dosage
Diet, High-Fat
Dimethyl Fumarate administration & dosage
Hypertension etiology
Hypertension prevention & control
Maternal Exposure
NF-E2-Related Factor 2 agonists
Prenatal Exposure Delayed Effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31416234
- Full Text :
- https://doi.org/10.3390/ijms20163957