PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy

Peripheral nerve degeneration after nerve injury is accompanied with oxidative stress that may activate poly ADP-ribose polymerase (PARP, DNA repair enzyme). PARP overactivation amplifies the neuronal damage either due to energy crisis or through inflammatory process by facilitating nuclear factor k...

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Bibliographic Details
Published in:Life sciences (1973) 2016-04, Vol.150, p.50-60
Main Authors: Komirishetty, Prashanth, Areti, Aparna, Yerra, Veera Ganesh, PK, Ruby, Sharma, Shyam S., Gogoi, Ranadeep, Sistla, Ramakrishna, Kumar, Ashutosh
Format: Article
Language:English
Subjects:
1,5-Isoquinolinediol
3-Aminobenzamide
Animals
Benzamides - therapeutic use
Constriction, Pathologic - complications
Constriction, Pathologic - drug therapy
Constriction, Pathologic - metabolism
Cyclooxygenase 2 - biosynthesis
Hyperalgesia - drug therapy
Inflammation - metabolism
Male
NAD - metabolism
Neuritis - drug therapy
Neuritis - etiology
Neuroinflammation
Neuroprotective Agents - therapeutic use
NF-κB
Nitrotyrosine and PAR
Oxidative Stress - drug effects
Pain Measurement - drug effects
Peripheral Nervous System Diseases - drug therapy
Peripheral Nervous System Diseases - etiology
Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use
Rats
Rats, Sprague-Dawley
Sensation - drug effects
Tyrosine - analogs & derivatives
Tyrosine - biosynthesis
Walking
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Summary:Peripheral nerve degeneration after nerve injury is accompanied with oxidative stress that may activate poly ADP-ribose polymerase (PARP, DNA repair enzyme). PARP overactivation amplifies the neuronal damage either due to energy crisis or through inflammatory process by facilitating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hence investigated the role of PARP inhibitors, 3-Aminobenzamide (3-AB) and 1,5-isoquinolinediol (ISO) in the attenuation of chronic constriction injury (CCI) induced peripheral neuropathy in rats. 3-AB and ISO (at doses 30 and 3mg/kg i.p., respectively) were tested in rats subjected to standard tests for evaluating hyperalgesia and allodynia. Sciatic functional index (SFI) was assessed by performing walking track analysis. Oxidative stress and inflammation induced biochemical alterations were estimated after 14days in sciatic nerve and lumbar spinal cord. Molecular changes were explored by immunohistochemistry and DNA fragmentation by TUNEL assay. Treatment significantly improved sensorimotor responses (p
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2016.02.085