Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis.
Rats
Animals
Pentoxifylline
/ pharmacology
Rolipram
/ pharmacology
Diabetic Neuropathies
/ metabolism
Caspase 3
/ metabolism
Cytochromes c
/ metabolism
Ganglia, Spinal
/ metabolism
bcl-2-Associated X Protein
/ metabolism
Phosphodiesterase Inhibitors
/ pharmacology
Apoptosis
Neurons
/ metabolism
Adenosine Triphosphate
/ metabolism
Mitochondria
Diabetes Mellitus
/ metabolism
apoptosis
diabetic neuropathy
dorsal root ganglion neurons
mitochondrial dysfunction
phosphodiesterase inhibitors
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
20
06
2023
received:
22
02
2023
accepted:
04
07
2023
medline:
10
11
2023
pubmed:
11
7
2023
entrez:
11
7
2023
Statut:
ppublish
Résumé
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.
Substances chimiques
Pentoxifylline
SD6QCT3TSU
Rolipram
K676NL63N7
Caspase 3
EC 3.4.22.-
Cytochromes c
9007-43-6
bcl-2-Associated X Protein
0
Phosphodiesterase Inhibitors
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23459Subventions
Organisme : Iran University of Medical Sciences
ID : IR.IUMS.REC. 95-04-118-29924
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
G. J. Bönhof, C. Herder, A. Strom, N. Papanas, M. Roden, D. Ziegler, Endocr. Rev. 2019, 40(1), 153.
A. A. Amour, N. Chamba, J. Kayandabila, I. A. Lyaruu, D. Marieke, E. R. Shao, W. Howlett, Int. J. Endocrinol. 2019, 2019, 5404781.
J. W. Russell, L. A. Zilliox, Continuum (Minneap Minn) 2014, 1226, 40.
A. Hosseini, M. Abdollahi, Oxid. Med. Cell Longev. 2013, 2013, 168039.
P. Fernyhough, Curr. Diab. Rep. 2015, 15, 89.
A. M. Vincent, J. L. Edwards, L. L. McLean, Y. Hong, F. Cerri, I. Lopez, A. Quattrini, E. L. Feldman, Acta Neuropathol. 2010, 120, 477.
G. M. Leinninger, J. L. Edwards, M. J. Lipshaw, E. L. Feldman, Nat. Clin. Pract. Neurol. 2006, 2(11), 620.
H. K. Kim, J. Y. Kwon, C. Yoo, S. Abdi, Anesth. Analg. 2015, 121(3), 822.
M. D. Houslay, D. R. Adams, Biochem. J. 2003, 370(1), 1.
P. Grafe, H. Bostock, U. Schneider, J. Physiol. 1994, 480(2), 297.
N. Volakakis, B. Kadkhodaei, E. Joodmardi, K. Wallis, L. Panman, J. Silvaggi, B. M. Spiegelman, T. Perlmann, Proc. Nat. Acad. Sci. 2010, 107(27), 12317.
S. S. Hannila, M. T. Filbin, Exp. Neurol. 2008, 209(2), 321.
J.-D. Troadec, M. Marien, S. Mourlevat, T. Debeir, M. Ruberg, F. Colpaert, P. P. Michel, Mol. Pharmacol. 2002, 62(5), 1043.
E. Nikulina, J. L. Tidwell, H. N. Dai, B. S. Bregman, M. T. Filbin, Proc. Nat. Acad. Sci. 2004, 101(23), 8786.
C. M. Whitaker, E. Beaumont, M. J. Wells, D. S. K. Magnuson, M. Hetman, S. M. Onifer, Neurosci. Lett. 2008, 438(2), 200.
F. A. O. Garcia, J. F. Rebouças, T. Q. Balbino, T. G. da Silva, C. H. R. de Carvalho-Júnior, G. S. Cerqueira, G. A. C. Brito, G. S. B. Viana, J. Inflamm. 2015, 12(1), 33.
H. K. Kim, S.-H. Hwang, S. O. Lee, S. H. Kim, S. Abdi, Pain. Physician. 2016, 19(4), 589.
S. Kreth, C. Ledderose, B. Luchting, F. Weis, M. Thiel, Shock 2010, 34(1), 10.
Z. Akbari, P. Reisi, A. Torkaman-Boutorabi, M. Farahmandfar, Int. J. Prev. Med. 2020, 11, 151.
J. H. Park, S. E. Kim, J. J. Jin, H. S. Choi, C. J. Kim, I. G. Ko, Int. Neurourol. J. 2016, 20(2), 107.
S. K. Muchhala, K. E. Benzeroual, Adv. Biosci. Biotechnol. 2012, 3(06), 731.
J. Liu, X. Feng, M. Yu, W. Xie, X. Zhao, W. Li, R. Guan, J. Xu, Neurosci. Lett. 2007, 412(3), 268.
K. L. COHEN, Ann. Intern. Med. 1987, 107(4), 600.
S. M. Cohen, T. Mathews, Angiology 1991, 42(9), 741.
F. Hosseini, A. Mohammadbeigi, M. Aghaali, R. Borujerdi, M. Parham, JRMS 2019, 24, 89.
R. B. Kalmansohn, R. W. Kalmansohn, C. H. Markham, D. L. Schiff, Angiology 1988, 39(4), 371.
Y. Lee, M. Robinson, N. Wong, E. Chan, M. A. Charles, JDC 1997, 11(5), 274.
M. Radfar, B. Larijani, M. Hadjibabaie, B. Rajabipour, A. Mojtahedi, M. Abdollahi, Biomed. Pharmacother. 2005, 59(6), 302.
E. P. Davidson, L. J. Coppey, B. Dake, M. A. Yorek, Exp. Diabetes. Res. 2011, 2011, 810469.
K.-H. Han, S.-H. Kim, I. C. Jeong, Y.-H. Lee, S.-J. Chang, S. W. Kim, JKNS 2012, 52(1), 32.
H. Halis, S. Bitiktaş, O. Baştuğ, B. Tan, Ş. Kavraal, T. Güneş, C. Süer, Clin. Psychopharmacol. Neurosci. 2019, 17(3), 388.
J. Mokry, M. Joskova, D. Mokra, I. Christensen, G. Nosalova, Adv. Exp. Med. Biol. 2013, 756, 57.
N. Sadeghiyan Galeshkalami, M. Abdollahi, R. Najafi, M. Baeeri, A. Jamshidzade, R. Falak, M. Davoodzadeh Gholami, G. Hassanzadeh, T. Mokhtari, S. Hassani, M. Rahimifard, A. Hosseini, Life Sci. 2019, 216, 101.
R. Najafi, A. Hosseini, H. Ghaznavi, S. Mehrzadi, A. M. Sharifi, Brain Res. Bull. 2017, 131, 117.
N. Namazi Sarvestani, S. Saberi Firouzi, R. Falak, M. Y. Karimi, M. Davoodzadeh Gholami, A. Rangbar, A. Hosseini, Metab. Brain Dis. 2018, 33, 1293.
M. A. Giembycz, R. Newton, Phosphod. Drug Targ. 2011, (204), 415.
L. Sun, Q. Xu, W. Zhang, C. Jiao, H. Wu, X. Chen, BMC Neurosci. 2019, 20(1), 28.
A. M. Schmeichel, J. D. Schmelzer, P. A. Low, Diabetes 2003, 52(1), 165.
S. K. R. Chowdhury, D. R. Smith, P. Fernyhough, Neurobiol. Dis. 2013, 51, 56.
J. W. Russell, D. Golovoy, A. M. Vincent, P. Mahendru, J. A. Olzmann, A. Mentzer, E. L. Feldman, FASEB. J. 2002, 16(13), 1738.
G. Kroemer, Nat. Med. 1997, 3(6), 614.
N. A. Thornberry, Y. Lazebnik, Science 1998, 281(5381), 1312.
M. Kishi, J. Tanabe, J. D. Schmelzer, P. A. Low, Diabetes 2002, 51(3), 819.
R. Najafi, A. M. Sharifi, A. Hosseini, Metab. Brain Dis. 2015, 30(3), 731.
H. Ghaznavi, R. Najafi, S. Mehrzadi, A. Hosseini, N. Tekyemaroof, A. Shakeri-Zadeh, M. Rezayat, A. M. Sharifi, Neurol. Res. 2015, 37(7), 624.
K. Azar Aghazadeh, B. Maryam, P. Borna, R. Mahshid, V. Gelareh, H. Shokoufeh, H. Asieh, H. Gholamreza, D. Ahmad Reza, S. Mohammad, Acta Med. Iran. 2018, 56(3), 151.
S. Firouzi, N. Sarvestani, A. Bakhtiarian, M. Ghazi-Khansari, M. Karimi, A. Ranjbar, M. Safa, A. Hosseini, Neurol. Res. 2018, 40, 1.
Y. Shi, J. Lv, L. Chen, G. Luo, M. Tao, J. Pan, X. Hu, J. Sheng, S. Zhang, M. Zhou, H. Fan, Front. Aging Neurosci. 2021, 13, 722580.
Y. Wang, S. Gao, V. Zheng, L. Chen, M. Ma, S. Shen, J. Qu, H. Zhang, M. E. Gurney, J. M. O'Donnell, Y. Xu, Front. Cell. Dev. Biol. 2020, 8, 599389.
S. Peng, H. Z. Yan, P. R. Liu, X. W. Shi, C. L. Liu, Q. Liu, Y. Zhang, Cell. Physiol. Biochem. 2018, 45(6), 2329.
J. Zhong, H. Yu, C. Huang, Q. Zhong, Y. Chen, J. Xie, Z. Zhou, J. Xu, H. Wang, Redox Biol. 2018, 16, 47.
C. Wang, X. M. Yang, Y. Y. Zhuo, H. Zhou, H. B. Lin, Y. F. Cheng, J. P. Xu, H. T. Zhang, Int. J. Neuropsychopharmacol. 2012, 15(6), 749.
H. Flint, M. A. Cotter, N. E. Cameron, Int. J. Exp. Diabetes. Res. 2000, 1(1), 49.
H. M. El-Sadek, M. Y. Al-Shorbagy, M. M. Awny, D. M. Abdallah, H. S. El-Abhar, J. Pharmacol. Sci. 2021, 146(3), 136.
S. Heiden, N. Vignon-Zellweger, S. Masuda, K. Yagi, K. Nakayama, M. Yanagisawa, N. Emoto, PLoS One 2014, 9(2), e88730.
Z. Nadia Sharifi, S. Movassaghi, F. Mohamadzadeh, S. Soleimani Asl, B. Pourheydar, M. Mehdizadeh, MJIR 2015, 29, 193.
T. J. Huang, N. M. Sayers, A. Verkhratsky, P. Fernyhough, Exp. Neurol. 2005, 194(1), 279.
B. Gong, O. V. Vitolo, F. Trinchese, S. Liu, M. Shelanski, O. Arancio, J. Clin. Invest. 2004, 114(11), 1624.
K. R. Neves, H. V. Nobre, Jr. L. K. Leal, G. M. de Andrade, G. A. Brito, G. S. Viana, Parkinson's Dis. 2015, 2015, 108179.
S. H. Kim, B. N. R. Park, S. W. Kim, J. Korean Neurosurg. Soc. 2011, 50(2), 109.