2. Academic Validation
  3. Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina

Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina

  • Biomed Pharmacother. 2022 Aug;152:113117. doi: 10.1016/j.biopha.2022.113117.
Shirui Dai 1,  Chao Wang 2,  Lemeng Feng 2,  Cheng Zhang 2,  Wulong Zhang 2,  Ye He 2,  Xuezhi Zhou 2,  Xiaobo Xia 2,  Baihua Chen 3,  Weitao Song 4
Affiliations

Affiliations

  • 1 National Clinical Research Center for Geriatric Diseases, Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China; Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, Hunan 410008, PR China; Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, PR China.
  • 2 National Clinical Research Center for Geriatric Diseases, Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China; Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, Hunan 410008, PR China.
  • 3 Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China; Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, PR China. Electronic address: chenbaihua2017@csu.edu.cn.
  • 4 National Clinical Research Center for Geriatric Diseases, Xiangya Hospital of Central South University, Changsha, Hunan 410008, PR China; Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of Ophthalmology, Changsha, Hunan 410008, PR China. Electronic address: wtsong1980@126.com.
PMID: 35653886 DOI: 10.1016/j.biopha.2022.113117
Abstract

Glutamate excitotoxicity can cause cell damage and Apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced Apoptosis, production of intracellular Reactive Oxygen Species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent Apoptosis.

Keywords

Apoptosis; Glutamate excitotoxicity; Nrf2; Oxidative stress; Retina; tBHQ.

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