TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways.
Animals
Antioxidants
/ pharmacology
Hydroquinones
/ pharmacology
Male
Methamphetamine
/ adverse effects
NF-E2-Related Factor 2
/ metabolism
Neurotoxicity Syndromes
/ drug therapy
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats
Rats, Wistar
Signal Transduction
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
01
2020
revised:
03
03
2020
accepted:
17
03
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
5
2
2021
Statut:
epublish
Résumé
Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.
Identifiants
pubmed: 32351675
doi: 10.1155/2020/8787156
pmc: PMC7174937
doi:
Substances chimiques
Antioxidants
0
Hydroquinones
0
NF-E2-Related Factor 2
0
Methamphetamine
44RAL3456C
2-tert-butylhydroquinone
C12674942B
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8787156Informations de copyright
Copyright © 2020 Xianyi Meng et al.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare.
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