Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways

Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways Publisher Pubmed

Namazi Sarvestani N¹ ; Saberi Firouzi S² ; Falak R³ ; Karimi MY⁴ ; Davoodzadeh Gholami M³ ; Rangbar A⁵ ; Hosseini A⁴

Show Affiliations

1. Department of Animal Biology, School of Biology, Department of Science, University of Tehran, Tehran, Iran
2. Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
5. Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

Source: Metabolic Brain Disease Published:2018

Abstract

Diabetic neuropathy (DN) is the most common diabetic complication. It is estimated diabetic population will increase to 592 million by the year 2035. This is while at least 50–60% of all diabetic patients will suffer from neuropathy in their lifetime. Oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial pathways in development and progression of DN. Since there is also no selective and effective therapeutic agent to prevent or treat high glucose (HG)-induced neuronal cell injury, it is crucial to explore tools by which one can reduce factors related to these pathways. Phosphodiesterase 4 and 7 (PDE 4 and 7) regulate oxidative damage, neurodegenaration, and inflammatory responses through modulation of cyclic adenosine monophosphate (cAMP) level, and thus can be as important drug targets for regulating DN. The aim of this study was to evaluate the protective effects of inhibitors of PDE 4 and 7, named rolipram and BRL5048, on HG-induced neurotoxicity in PC12 cells as an in vitro cellular model for DN and determine the possible mechanisms for theirs effects. We report that the PC12 cells pre-treatment with rolipram (2 μM) and/or BRL5048 (0.2 μM) for 60 min and then exposing the cells to HG (4.5 g/L for 72 h) or normal glucose (NG) (1 g/L for 72 h) condition show: (1) significant attenuation in ROS, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, MMP and ATP levels. All these data together led us to propose PDE 4 and 7 inhibitors, and specifically, rolipram and BRL5048, as potential drugs candidate to be further studied for the prevention and treatment of DN. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

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Style	Citing Format
MLA	Namazi Sarvestani N, et al.. "Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways." Metabolic Brain Disease, vol. 33, no. 4, 2018, pp. 1293-1306.
APA	Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, Hosseini A (2018). Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways. Metabolic Brain Disease, 33(4), 1293-1306.
Chicago	Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, Hosseini A. "Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways." Metabolic Brain Disease 33, no. 4 (2018): 1293-1306.
Harvard	Namazi Sarvestani N et al. (2018) 'Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways', Metabolic Brain Disease, 33(4), pp. 1293-1306.
Vancouver	Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, et al.. Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways. Metabolic Brain Disease. 2018;33(4):1293-1306.
BibTex	@article{ author = {Namazi Sarvestani N and Saberi Firouzi S and Falak R and Karimi MY and Davoodzadeh Gholami M and Rangbar A and Hosseini A}, title = {Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways}, journal = {Metabolic Brain Disease}, volume = {33}, number = {4}, pages = {1293-1306}, year = {2018} }
RIS	TY - JOUR AU - Namazi Sarvestani N AU - Saberi Firouzi S AU - Falak R AU - Karimi MY AU - Davoodzadeh Gholami M AU - Rangbar A AU - Hosseini A TI - Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways JO - Metabolic Brain Disease VL - 33 IS - 4 SP - 1293 EP - 1306 PY - 2018 ER -

Style

Citing Format

MLA

Namazi Sarvestani N, et al.. "Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways." Metabolic Brain Disease, vol. 33, no. 4, 2018, pp. 1293-1306.

APA

Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, Hosseini A (2018). Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways. Metabolic Brain Disease, 33(4), 1293-1306.

Chicago

Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, Hosseini A. "Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways." Metabolic Brain Disease 33, no. 4 (2018): 1293-1306.

Harvard

Namazi Sarvestani N et al. (2018) 'Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways', Metabolic Brain Disease, 33(4), pp. 1293-1306.

Vancouver

Namazi Sarvestani N, Saberi Firouzi S, Falak R, Karimi MY, Davoodzadeh Gholami M, Rangbar A, et al.. Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways. Metabolic Brain Disease. 2018;33(4):1293-1306.

BibTex

@article{ author = {Namazi Sarvestani N and Saberi Firouzi S and Falak R and Karimi MY and Davoodzadeh Gholami M and Rangbar A and Hosseini A}, title = {Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways}, journal = {Metabolic Brain Disease}, volume = {33}, number = {4}, pages = {1293-1306}, year = {2018} }

RIS

TY - JOUR
AU - Namazi Sarvestani N
AU - Saberi Firouzi S
AU - Falak R
AU - Karimi MY
AU - Davoodzadeh Gholami M
AU - Rangbar A
AU - Hosseini A
TI - Phosphodiesterase 4 and 7 Inhibitors Produce Protective Effects Against High Glucose-Induced Neurotoxicity in Pc12 Cells Via Modulation of the Oxidative Stress, Apoptosis and Inflammation Pathways
JO - Metabolic Brain Disease
VL - 33
IS - 4
SP - 1293
EP - 1306
PY - 2018
ER -

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