PMID- 35204242
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220228
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 2
DP  - 2022 Feb 11
TI  - Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in 
      Adolescent Rats Exposed to Binge Drinking.
LID - 10.3390/antiox11020362 [doi]
LID - 362
AB  - Chronic ethanol consumption and liver disease are intimately related to folic 
      acid (FA) homeostasis. Despite the fact that FA decreases lipid oxidation, its 
      mechanisms are not yet well elucidated. Lately, adolescents have been practising 
      binge drinking (BD), consisting of the intake of a high amount of alcohol in a 
      short time; this is a particularly pro-oxidant form of consumption. The aim of 
      this study is to examine, for the first time, FA homeostasis in BD adolescent 
      rats and its antioxidant properties in the liver. We used adolescent rats, 
      including control rats and rats exposed to an intermittent intraperitoneal BD 
      model, supplemented with or without FA. Renal FA reabsorption and renal FA 
      deposits were increased in BD rats; hepatic deposits were decreased, and heart 
      and serum levels remained unaffected. This depletion in the liver was accompanied 
      by higher transaminase levels; an imbalance in the antioxidant endogenous 
      enzymatic system; lipid and protein oxidation; a decrease in glutathione (GSH) 
      levels; hyper-homocysteinemia (HHcy); an increase in NADPH oxidase (NOX) 1 and 
      NOX4 enzymes; an increase in caspase 9 and 3; and a decrease in the 
      anti-apoptotic metallopeptidase inhibitor 1. Furthermore, BD exposure increased 
      the expression of uncoupled endothelial nitric oxide synthase (eNOS) by 
      increasing reactive nitrogen species generation and the nitration of tyrosine 
      proteins. When FA was administered, hepatic FA levels returned to normal levels; 
      transaminase and lipid and protein oxidation also decreased. Its antioxidant 
      activity was due, in part, to the modulation of superoxide dismutase activity, 
      GSH synthesis and NOX1, NOX4 and caspase expression. FA reduced HHcy and 
      increased the expression of coupled eNOS by increasing tetrahydrobiopterin 
      expression, avoiding nitrosative stress. In conclusion, FA homeostasis and its 
      antioxidant properties are affected in BD adolescent rats, making it clear that 
      this vitamin plays an important role in the oxidative, nitrosative and apoptotic 
      hepatic damage generated by acute ethanol exposure. For this, FA supplementation 
      becomes a potential BD therapy for adolescents, preventing future acute 
      alcohol-related harms.
FAU - Gallego-Lopez, Maria Del Carmen
AU  - Gallego-Lopez MDC
AUID- ORCID: 0000-0003-2272-5603
AD  - Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, 
      Spain.
FAU - Ojeda, Maria Luisa
AU  - Ojeda ML
AUID- ORCID: 0000-0002-9160-2749
AD  - Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, 
      Spain.
FAU - Romero-Herrera, Ines
AU  - Romero-Herrera I
AD  - Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, 
      Spain.
FAU - Nogales, Fatima
AU  - Nogales F
AUID- ORCID: 0000-0003-4844-2740
AD  - Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, 
      Spain.
FAU - Carreras, Olimpia
AU  - Carreras O
AD  - Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, 
      Spain.
LA  - eng
GR  - CTS-193/Regional Government of Andalusia/
PT  - Journal Article
DEP - 20220211
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC8868551
OTO - NOTNLM
OT  - apoptosis
OT  - binge drinking
OT  - folic acid
OT  - nitrosative stress
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2022/02/26 06:00
MHDA- 2022/02/26 06:01
PMCR- 2022/02/11
CRDT- 2022/02/25 01:03
PHST- 2021/12/15 00:00 [received]
PHST- 2022/01/21 00:00 [revised]
PHST- 2022/02/08 00:00 [accepted]
PHST- 2022/02/25 01:03 [entrez]
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/02/26 06:01 [medline]
PHST- 2022/02/11 00:00 [pmc-release]
AID - antiox11020362 [pii]
AID - antioxidants-11-00362 [pii]
AID - 10.3390/antiox11020362 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Feb 11;11(2):362. doi: 10.3390/antiox11020362.