Journal article
Poly(ADP-Ribose) Polymerase Inhibition Alleviates Experimental Diabetic Sensory Neuropathy
Diabetes (New York, N.Y.), Vol.55(6), pp.1686-1694
06/2006
DOI: 10.2337/db06-0067
PMCID: PMC2228258
PMID: 16731831
Abstract
Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg · kg
−1
· day
−1
i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADP-ribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses, including thermal and mechanical hyperalgesia and tactile allodynia as well as exaggerated formalin flinching behavior in diabetic rats, without affecting the aforementioned variables in the control group. Poly(ADP-ribose) and, to a lesser extent, nitrotyrosine abundance in sciatic nerve, as well as superoxide and nitrotyrosine formation in vasa nervorum, were markedly reduced by ISO therapy. Apoptosis in dorsal root ganglion neurons (transferase-mediated dUTP nick-end labeling assay) was not detected in any of the groups. In conclusion, PARP activation contributes to early diabetic sensory neuropathy by mechanisms that may include oxidative stress but not neuronal apoptosis.
Details
- Title: Subtitle
- Poly(ADP-Ribose) Polymerase Inhibition Alleviates Experimental Diabetic Sensory Neuropathy
- Creators
- Olga Ilnytska - Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LouisianaValeriy V Lyzogubov - Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LouisianaMartin J Stevens - Department of Internal Medicine, University of Michigan, Ann Arbor, MichiganViktor R Drel - Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LouisianaNazar Mashtalir - Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LouisianaPal Pacher - Laboratory of Physiological Studies, National Insitutes of Health/National Institute on Alcohol Abuse and Alcoholism, Bethesda, MarylandMark A Yorek - Veteran Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, IowaIrina G Obrosova - Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.55(6), pp.1686-1694
- DOI
- 10.2337/db06-0067
- PMID
- 16731831
- PMCID
- PMC2228258
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Language
- English
- Date published
- 06/2006
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094486202771
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