PMID- 37755222
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230930
IS  - 2077-0375 (Print)
IS  - 2077-0375 (Electronic)
IS  - 2077-0375 (Linking)
VI  - 13
IP  - 9
DP  - 2023 Sep 17
TI  - Exploring the Role of Drug Repurposing in Bridging the Hypoxia-Depression 
      Connection.
LID - 10.3390/membranes13090800 [doi]
LID - 800
AB  - High levels of oxidative stress are implicated in hypoxia, a physiological 
      response to low levels of oxygen. Evidence supports a connection between this 
      response and depression. Previous studies indicate that tryptophan hydroxylase 
      can be negatively affected in hypoxia, impairing serotonin synthesis and 
      downstream pathways. Some studies also hypothesize that increasing 
      hypoxia-inducible factor-1 (HIF-1) levels may be a new therapeutic modality for 
      depression. Hence, this study delved into the influence of hypoxia on the 
      cellular response to drugs designed to act in depression. By the induction of 
      hypoxia in SH-SY5Y cells through a hypoxia incubator chamber or Cobalt Chloride 
      treatment, the effect of Mirtazapine, an antidepressant, and other drugs that 
      interact with serotonin receptors (TCB-2, Dextromethorphan, Ketamine, Quetiapine, 
      Scopolamine, Celecoxib, and Lamotrigine) on SH-SY5Y cellular viability and 
      morphology was explored. The selection of drugs was initially conducted by 
      literature search, focusing on compounds with established potential for 
      employment in depression therapy. Subsequently, we employed in silico approaches 
      to forecast their ability to traverse the blood-brain barrier (BBB). This step 
      was particularly pertinent as we aimed to assess their viability for inducing 
      potential antidepressant effects. The effect of these drugs in hypoxia under the 
      inhibition of HIF-1 by Echinomycin was also tested. Our results revealed that all 
      the potential repurposed drugs promoted cell viability, especially when hypoxia 
      was chemically induced. When combined with Echinomycin, all drugs decreased 
      cellular viability, possibly by the inability to interact with HIF-1.
FAU - Correia, Ana Salome
AU  - Correia AS
AUID- ORCID: 0000-0002-8231-1560
AD  - OncoPharma Research Group, Center for Health Technology and Services Research 
      (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal.
AD  - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor 
      Hernani Monteiro, 4200-319 Porto, Portugal.
AD  - Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua 
      de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
FAU - Marques, Lara
AU  - Marques L
AUID- ORCID: 0000-0002-7003-4957
AD  - OncoPharma Research Group, Center for Health Technology and Services Research 
      (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal.
AD  - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor 
      Hernani Monteiro, 4200-319 Porto, Portugal.
AD  - Department of Community Medicine, Information and Health Decision Sciences 
      (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Placido da Costa, 
      4200-450 Porto, Portugal.
FAU - Cardoso, Armando
AU  - Cardoso A
AUID- ORCID: 0000-0002-2967-6990
AD  - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor 
      Hernani Monteiro, 4200-319 Porto, Portugal.
AD  - NeuroGen Research Group, Center for Health Technology and Services Research 
      (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal.
AD  - Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of 
      Porto, Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal.
FAU - Vale, Nuno
AU  - Vale N
AUID- ORCID: 0000-0002-1283-1042
AD  - OncoPharma Research Group, Center for Health Technology and Services Research 
      (CINTESIS), Rua Doutor Placido da Costa, 4200-450 Porto, Portugal.
AD  - CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor 
      Hernani Monteiro, 4200-319 Porto, Portugal.
AD  - Department of Community Medicine, Information and Health Decision Sciences 
      (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Placido da Costa, 
      4200-450 Porto, Portugal.
LA  - eng
PT  - Journal Article
DEP - 20230917
PL  - Switzerland
TA  - Membranes (Basel)
JT  - Membranes
JID - 101577807
PMC - PMC10537732
OTO - NOTNLM
OT  - Echinomycin
OT  - cobalt chloride
OT  - drug repurposing
OT  - hypoxia-inducible factor-1
OT  - serotonin receptors
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/27 12:41
MHDA- 2023/09/27 12:42
PMCR- 2023/09/17
CRDT- 2023/09/27 09:54
PHST- 2023/08/05 00:00 [received]
PHST- 2023/09/05 00:00 [revised]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/09/27 12:42 [medline]
PHST- 2023/09/27 12:41 [pubmed]
PHST- 2023/09/27 09:54 [entrez]
PHST- 2023/09/17 00:00 [pmc-release]
AID - membranes13090800 [pii]
AID - membranes-13-00800 [pii]
AID - 10.3390/membranes13090800 [doi]
PST - epublish
SO  - Membranes (Basel). 2023 Sep 17;13(9):800. doi: 10.3390/membranes13090800.