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Neurotox Res. 2017 Jan;31(1):31-45. doi: 10.1007/s12640-016-9658-9. Epub 2016 Aug 27.

Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina.

Author information

1
Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia.
2
Center for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Jalan Hospital, Sungai Buloh Campus, Sungai Buloh, 47000, Selangor Darul Ehsan, Malaysia. iezhitsa@yandex.ru.
3
Research Institute of Pharmacology, Volgograd State Medical University, 1, Pavshikh Bortsov sq., Volgograd, Russian Federation, 400131. iezhitsa@yandex.ru.
4
Department of Ophthalmology, IMU Clinical School, International Medical University, Jalan Rasah, Seremban, Malaysia.
5
Research Institute of Pharmacology, Volgograd State Medical University, 1, Pavshikh Bortsov sq., Volgograd, Russian Federation, 400131.

Abstract

Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients. The purpose of the present study was to examine the potential neuroprotective effect of Mg acetyltaurate (MgAT) on RGC death induced by NMDA. MgAT was proposed mainly due to the combination of magnesium (Mg) and taurine which may provide neuroprotection by dual mechanisms of action, i.e., inhibition of NMDA receptors and antioxidant effects. Rats were divided into 5 groups and were given intravitreal injections. Group 1 (PBS group) was injected with vehicle; group 2 (NMDA group) was injected with NMDA while groups 3 (pre-), 4 (co-), and 5 (post-) treatments were injected with MgAT, 24 h before, in combination or 24 h after NMDA injection respectively. NMDA and MgAT were injected in PBS at doses 160 and 320 nmol, respectively. Seven days after intravitreal injection, the histological changes in the retina were evaluated using hematoxylin & eosin (H&E) staining. Optic nerves were dissected and stained in Toluidine blue for grading on morphological neurodegenerative changes. The extent of apoptosis in retinal tissue was assessed by TUNEL assay and caspase-3 immunohistochemistry staining. The estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors and caspase-3 activity in retina was done using enzyme-linked immunosorbent assay (ELISA) technique. The retinal morphometry showed reduced thickness of ganglion cell layer (GCL) and reduction in the number of retinal cells in GCL in NMDA group compared to the MgAT-treated groups. TUNEL and caspase-3 staining showed increased number of apoptotic cells in inner retina. The results were further corroborated by the estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors, and caspase-3 activity in retina. In conclusion, current study revealed that intravitreal MgAT prevents retinal and optic nerve damage induced by NMDA. Overall, our data demonstrated that the pretreatment with MgAT was more effective than co- and posttreatment. This protective effect of MgAT against NMDA-induced retinal cell apoptosis could be attributed to the reduction of retinal oxidative stress and activation of BDNF-related neuroprotective mechanisms.

KEYWORDS:

Excitotoxicity; Glaucoma; Magnesium acetyltaurate; NMDA; Neuroprotection; RGC apoptosis

PMID:
27568334
DOI:
10.1007/s12640-016-9658-9
[Indexed for MEDLINE]

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