PMID- 34970151
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220101
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Neuroprotection Against NMDA-Induced Retinal Damage by Philanthotoxin-343 
      Involves Reduced Nitrosative Stress.
PG  - 798794
LID - 10.3389/fphar.2021.798794 [doi]
LID - 798794
AB  - N-methyl-D-aspartate receptor (NMDAR) overstimulation is known to mediate 
      neurodegeneration, and hence represents a relevant therapeutic target for 
      neurodegenerative disorders including glaucoma. This study examined the 
      neuroprotective effects of philanthotoxin (PhTX)-343 against NMDA-induced retinal 
      injury in rats. Male Sprague Dawley rats were divided into three groups; group 1 
      received phosphate buffer saline as the negative control, group 2 was injected 
      with NMDA (160 nM) to induce retinal excitotoxic injury, and group 3 was 
      pre-treated with PhTX-343 (160 nM) 24 h before NMDA exposure. All treatments were 
      given intravitreally and bilaterally. Seven days post-treatment, rats were 
      subjected to visual behaviour assessments using open field and colour recognition 
      tests. Rats were then euthanized, and the retinas were harvested and subjected to 
      haematoxylin and eosin (H&E) staining for morphometric analysis and 
      3-nitrotyrosine (3-NT) ELISA protocol as the nitrosative stress biomarker. 
      PhTX-343 treatment prior to NMDA exposure improved the ability of rats to 
      recognize visual cues and preserved visual functions (i.e., recognition of 
      objects with different colours). Morphological examination of retinal tissues 
      showed that the fractional ganglion cell layer thickness within the inner retina 
      (IR) in the PhTX-343 treated group was greater by 1.28-fold as compared to 
      NMDA-treated rats (p < 0.05) and was comparable to control rats (p > 0.05). 
      Additionally, the number of retinal cell nuclei/100 mum(2) in IR for the 
      PhTX-343-treated group was greater by 1.82-fold compared to NMDA-treated rats (p 
      < 0.05) and was comparable to control group (p > 0.05). PhTX-343 also reduced the 
      retinal 3-NT levels by 1.74-fold compared to NMDA-treated rats (p < 0.05). In 
      conclusion, PhTX-343 pretreatment protects against NMDA-induced retinal 
      morphological changes and visual impairment by suppressing nitrosative stress as 
      reflected by the reduced retinal 3-NT level.
CI  - Copyright (c) 2021 Mohamad, Abu, Fazel, Agarwal, Iezhitsa, Juliana, Mellor and 
      Franzyk.
FAU - Mohamad, Mohamad Haiqal Nizar
AU  - Mohamad MHN
AD  - Institute of Medical Science Technology, Universiti Kuala Lumpur, Kuala Lumpur, 
      Malaysia.
FAU - Abu, Izuddin Fahmy
AU  - Abu IF
AD  - Institute of Medical Science Technology, Universiti Kuala Lumpur, Kuala Lumpur, 
      Malaysia.
FAU - Fazel, Muhammad Fattah
AU  - Fazel MF
AD  - Institute of Medical Science Technology, Universiti Kuala Lumpur, Kuala Lumpur, 
      Malaysia.
FAU - Agarwal, Renu
AU  - Agarwal R
AD  - School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
FAU - Iezhitsa, Igor
AU  - Iezhitsa I
AD  - School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
AD  - Department of Pharmacology and Bioinformatics, Volgograd State Medical 
      University, Volgograd, Russian Federation.
FAU - Juliana, Norsham
AU  - Juliana N
AD  - Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Negeri 
      Sembilan, Malaysia.
FAU - Mellor, Ian R
AU  - Mellor IR
AD  - School of Life Sciences, Faculty of Medicine and Health Sciences, University of 
      Nottingham, Nottingham, United Kingdom.
FAU - Franzyk, Henrik
AU  - Franzyk H
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20211214
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8714026
OTO - NOTNLM
OT  - N-methyl-D-aspartate receptor
OT  - N-methyl-D-aspartate receptor overstimulation
OT  - excitotoxicity
OT  - glaucoma
OT  - neurodegeneration
OT  - philanthotoxin-343
OT  - retinal ganglion cell
OT  - visual behavioural analysis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/01 06:00
MHDA- 2022/01/01 06:01
PMCR- 2021/12/14
CRDT- 2021/12/31 06:02
PHST- 2021/10/20 00:00 [received]
PHST- 2021/11/10 00:00 [accepted]
PHST- 2021/12/31 06:02 [entrez]
PHST- 2022/01/01 06:00 [pubmed]
PHST- 2022/01/01 06:01 [medline]
PHST- 2021/12/14 00:00 [pmc-release]
AID - 798794 [pii]
AID - 10.3389/fphar.2021.798794 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Dec 14;12:798794. doi: 10.3389/fphar.2021.798794. 
      eCollection 2021.