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Selenium and Resveratrol Attenuated Diabetes Mellitus-Mediated Oxidative Retinopathy and Apoptosis via the Modulation of TRPM2 Activity in Mice

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Abstract

Diabetes mellitus induces optic nerve injury via the excessive generation of mitochondria reactive free oxygen radical (mitROS). TRPM2 channel is activated by mitROS, although it is inhibited by selenium (Se) and resveratrol (RSV). The activation of TRPM2 induces apoptosis and oxidative injury in the optic nerve. The inhibition of TRPM2 may decrease the optic nerve injury action of diabetes mellitus after the treatments of Se and RSV. Present study aimed to investigate the protective actions of Se and RSV on the excessive Ca2+ influx and mitROS generation-mediated optic nerve oxidative injury via the modulation of TRPM2. Fifty-six C57BL/6j male mice were divided into seven groups as control, Se, RSV, streptozotocin (STZ), STZ + Se, STZ + RSV, and STZ + Se + RSV. The STZ-mediated stimulation of TRPM2 increased the cytosolic Ca2+, lipid peroxidation, mitROS, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations in the mice, although their concentrations were decreased in the optic nerve by the treatments of Se and RSV. The STZ-induced decrease of optic nerve viability, glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations was also upregulated by the treatments of Se and RSV. The STZ-induced increase of TRPM2, PARP-1, caspase-3, and caspase-9 protein band expressions was diminished by the treatments of Se and RSV. In conclusion, STZ induced the optic nerve oxidative injury and apoptosis via the upregulation of TRPM2 stimulation, although the treatments of Se and RSV decreased the injury and apoptosis via the downregulation of TRPM2 activity.

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Data Availability

Row data and analyzed results are available from the corresponding author.

Abbreviations

2/APB:

2-Aminoethoxydiphenyl borate

ACA:

N-(p-Amylcinnamoyl)anthranilic acid

ADPR:

ADP-ribose

BF:

Bright field

Ca2 + :

Calcium ion

CASP/3:

Caspase-3

CASP/8:

Caspase-8

CASP/9:

Caspase-9

CLSM:

Confocal laser scanning microscope

cytCa2 + :

Cytosolic free calcium ion

cytROS:

Cytosolic free reactive oxygen radicals

DM:

Diabetes mellitus

DRG:

Dorsal root ganglion

GSH:

Glutathione

GSH/Px:

Glutathione peroxidase

MDA:

Lipid peroxidation

mitPOT:

Mitochondrial membrane potential

mitROS:

Mitochondrial free reactive oxygen radicals

PARP1:

Poly(ADP-ribose)polymerase-1

RSV:

Resveratrol

Se:

Selenium

TRP:

Transient receptor potential

TRPM2:

Transient receptor potential melastatin 2

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Funding

The present study was financially supported by BSN Health, Analyses, Innov., Consult., Org., Agricul., Industry LTD., Isparta, Turkey. (The number of the project is: 2021–05. The owner of the project is Dr. Hatice Daldal.)

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Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Medicine, Usak University, TR-64100, Usak, Turkey

    Hatice Daldal

  2. Neuroscience Research Center, Suleyman Demirel University, TR-32260, Isparta, Turkey

    Mustafa Nazıroğlu

  3. Drug Discovery Unit, BSN Health, Analyses, Innov., Consult., Org., Agricul., Ltd., TR-32260, Isparta, Turkey

    Mustafa Nazıroğlu

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  1. Hatice Daldal
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Contributions

Hatice Daldal and Mustafa Nazıroğlu planned the present hypothesis and the main manuscript text. The optic nerve isolation, cell culture, antioxidant, and cell viability analyses in the current study were performed by Hatice Daldal. The remaining analyses and graphic presentations were performed by Mustafa Nazıroğlu.

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Correspondence to Hatice Daldal.

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The authors declare that they have no conflicts of interest. There is no human sample in the current study.

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Daldal, H., Nazıroğlu, M. Selenium and Resveratrol Attenuated Diabetes Mellitus-Mediated Oxidative Retinopathy and Apoptosis via the Modulation of TRPM2 Activity in Mice. Biol Trace Elem Res 200, 2283–2297 (2022). https://doi.org/10.1007/s12011-022-03203-9

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