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Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina.
Neurotox Res. 2017 01; 31(1):31-45.NR

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27568334

Citation

Lambuk, Lidawani, et al. "Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina." Neurotoxicity Research, vol. 31, no. 1, 2017, pp. 31-45.
Lambuk L, Jafri AJ, Arfuzir NN, et al. Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina. Neurotox Res. 2017;31(1):31-45.
Lambuk, L., Jafri, A. J., Arfuzir, N. N., Iezhitsa, I., Agarwal, R., Rozali, K. N., Agarwal, P., Bakar, N. S., Kutty, M. K., Yusof, A. P., Krasilnikova, A., Spasov, A., Ozerov, A., & Ismail, N. M. (2017). Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina. Neurotoxicity Research, 31(1), 31-45. https://doi.org/10.1007/s12640-016-9658-9
Lambuk L, et al. Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina. Neurotox Res. 2017;31(1):31-45. PubMed PMID: 27568334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina. AU - Lambuk,Lidawani, AU - Jafri,Azliana Jusnida Ahmad, AU - Arfuzir,Natasha Najwa Nor, AU - Iezhitsa,Igor, AU - Agarwal,Renu, AU - Rozali,Khairul Nizam Bin, AU - Agarwal,Puneet, AU - Bakar,Nor Salmah, AU - Kutty,Methil Kannan, AU - Yusof,Ahmad Pauzi Md, AU - Krasilnikova,Anna, AU - Spasov,Alexander, AU - Ozerov,Alexander, AU - Ismail,Nafeeza Mohd, Y1 - 2016/08/27/ PY - 2016/02/14/received PY - 2016/08/09/accepted PY - 2016/07/31/revised PY - 2016/8/29/pubmed PY - 2017/7/29/medline PY - 2016/8/29/entrez KW - Excitotoxicity KW - Glaucoma KW - Magnesium acetyltaurate KW - NMDA KW - Neuroprotection KW - RGC apoptosis SP - 31 EP - 45 JF - Neurotoxicity research JO - Neurotox Res VL - 31 IS - 1 N2 - 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. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/27568334/Neuroprotective_Effect_of_Magnesium_Acetyltaurate_Against_NMDA_Induced_Excitotoxicity_in_Rat_Retina_ L2 - https://dx.doi.org/10.1007/s12640-016-9658-9 DB - PRIME DP - Unbound Medicine ER -