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
  • 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: [email protected].
  • 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: [email protected].
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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