Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis

Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis Publisher Pubmed

Dastgheib M¹ ; Falak R² ; Moghaddam MV² ; Hassanzadeh G³ ; Safa M⁴ ; Hosseini A¹

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1. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
2. Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
3. Department of Anatomy, Tehran University of Medical Sciences, Tehran, Iran
4. Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Journal of Biochemical and Molecular Toxicology Published:2023

Abstract

Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase-4 inhibitor (PDE-4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl-2, caspase-3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl-2, and caspase-3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN. © 2023 Wiley Periodicals LLC.

Style	Citing Format
MLA	Dastgheib M, et al.. "Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis." Journal of Biochemical and Molecular Toxicology, vol. 37, no. 11, 2023, pp. -.
APA	Dastgheib M, Falak R, Moghaddam MV, Hassanzadeh G, Safa M, Hosseini A (2023). Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis. Journal of Biochemical and Molecular Toxicology, 37(11), -.
Chicago	Dastgheib M, Falak R, Moghaddam MV, Hassanzadeh G, Safa M, Hosseini A. "Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis." Journal of Biochemical and Molecular Toxicology 37, no. 11 (2023): -.
Harvard	Dastgheib M et al. (2023) 'Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis', Journal of Biochemical and Molecular Toxicology, 37(11), pp. -.
Vancouver	Dastgheib M, Falak R, Moghaddam MV, Hassanzadeh G, Safa M, Hosseini A. Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis. Journal of Biochemical and Molecular Toxicology. 2023;37(11):-.
BibTex	@article{ author = {Dastgheib M and Falak R and Moghaddam MV and Hassanzadeh G and Safa M and Hosseini A}, title = {Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis}, journal = {Journal of Biochemical and Molecular Toxicology}, volume = {37}, number = {11}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Dastgheib M AU - Falak R AU - Moghaddam MV AU - Hassanzadeh G AU - Safa M AU - Hosseini A TI - Rolipram and Pentoxifylline Combination Ameliorates the Morphological Abnormalities of Dorsal Root Ganglion Neurons in Experimental Diabetic Neuropathy by Reducing Mitochondrial Dysfunction and Apoptosis JO - Journal of Biochemical and Molecular Toxicology VL - 37 IS - 11 SP - EP - PY - 2023 ER -

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