PMID- 36979006
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240510
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 3
DP  - 2023 Mar 20
TI  - 17beta-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and 
      Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic 
      Female Mice.
LID - 10.3390/antiox12030758 [doi]
LID - 758
AB  - Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed 
      predominantly in women. It is characterized by abnormal gastric emptying (GE) 
      without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory 
      neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It plays a 
      critical role in gastrointestinal (GI) motility and stomach emptying. Here, we 
      wanted to demonstrate the protective effects of supplemental 17beta-estradiol (E(2)) 
      on NO-mediated gastric function. We showed E(2) supplementation to alleviate 
      oxidative and inflammatory stress in streptozotocin (STZ)-induced diabetic female 
      mice. Our findings suggest that daily administration of E(2) at therapeutic doses 
      is beneficial for metabolic homeostasis. This restoration occurs via regulating 
      and modulating the expression/function of glycogen synthase kinase-3beta (GSK-3beta), 
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), Phase II enzymes, MAPK- 
      and nuclear factor kappa-light-chain-enhancer of activated B cells 
      (NFkB)-mediated inflammatory cytokines (IL-1beta, IL-6, TNFalpha, IGF-1), and gastric 
      apoptotic regulators. We also showed E(2) supplementation to elevate GCH-1 
      protein levels in female diabetic mice. Since GCH-1 facilitates the production of 
      tetrahydrobiopterin (BH(4), cofactor for nNOS), an increase in GCH-1 protein 
      levels in diabetic mice may improve their GE and nitrergic function. Our findings 
      provide new insights into the impact of estrogen on gastric oxidative stress and 
      intracellular inflammatory cascades in the context of Gp.
FAU - Sprouse, Jeremy
AU  - Sprouse J
AD  - Department of Oral Diagnostic Sciences and Research, School of Dentistry, Meharry 
      Medical College, Nashville, TN 37208, USA.
AD  - Department of Endodontics, School of Dentistry, Meharry Medical College, 
      Nashville, TN 37208, USA.
FAU - Sampath, Chethan
AU  - Sampath C
AUID- ORCID: 0000-0002-6396-227X
AD  - Department of Oral Diagnostic Sciences and Research, School of Dentistry, Meharry 
      Medical College, Nashville, TN 37208, USA.
FAU - Gangula, Pandu
AU  - Gangula P
AUID- ORCID: 0000-0001-7259-570X
AD  - Department of Oral Diagnostic Sciences and Research, School of Dentistry, Meharry 
      Medical College, Nashville, TN 37208, USA.
LA  - eng
GR  - S21 MD000104/MD/NIMHD NIH HHS/United States
GR  - SC1 GM121282/GM/NIGMS NIH HHS/United States
GR  - U54 MD007586/MD/NIMHD NIH HHS/United States
GR  - SC1GM121282/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20230320
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10045314
OTO - NOTNLM
OT  - MAPK
OT  - NFkappaB
OT  - Nrf2
OT  - apoptosis
OT  - estradiol
OT  - estrogen receptors
OT  - gastroparesis
OT  - inflammation
OT  - nitrergic relaxation
OT  - nitric oxide
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/03/20
CRDT- 2023/03/29 01:17
PHST- 2023/02/02 00:00 [received]
PHST- 2023/03/09 00:00 [revised]
PHST- 2023/03/12 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/29 01:17 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/20 00:00 [pmc-release]
AID - antiox12030758 [pii]
AID - antioxidants-12-00758 [pii]
AID - 10.3390/antiox12030758 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Mar 20;12(3):758. doi: 10.3390/antiox12030758.