PMID- 27712995
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20180329
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 113
IP  - Pt A
DP  - 2017 Feb
TI  - Combination strategy of PARP inhibitor with antioxidant prevent bioenergetic 
      deficits and inflammatory changes in CCI-induced neuropathy.
PG  - 137-147
LID - S0028-3908(16)30437-3 [pii]
LID - 10.1016/j.neuropharm.2016.09.027 [doi]
AB  - Neuropathic pain, a debilitating pain condition and the underlying pathogenic 
      mechanisms are complex and interwoven amongst each other and still there is scant 
      information available regarding therapies which promise to treat the condition. 
      Evidence indicate that oxidative/nitrosative stress induced poly (ADP-ribose) 
      polymerase (PARP) overactivation initiate neuroinflammation and bioenergetic 
      crisis culminating into neurodegenerative changes following nerve injury. Hence, 
      we investigated the therapeutic effect of combining an antioxidant, quercetin and 
      a PARP inhibitor, 4-amino 1, 8-naphthalimide (4-ANI) on the hallmark deficits 
      induced by chronic constriction injury (CCI) of sciatic nerve in rats. Quercetin 
      (25 mg/kg, p.o.) and 4-ANI (3 mg/kg, p.o.) were administered either alone or in 
      combination for 14 days to examine sciatic functional index, allodynia and 
      hyperalgesia using walking track analysis, Von Frey, acetone spray and hot plate 
      tests respectively. Malondialdehyde, nitrite and glutathione levels were 
      estimated to detect oxidative/nitrosative stress; mitochondrial membrane 
      potential and cytochrome c oxidase activity to assess mitochondrial function; NAD 
      & ATP levels to examine the bioenergetic status and levels of inflammatory 
      markers were evaluated in ipsilateral sciatic nerve. Quercetin and 4-ANI alone 
      improved the pain behaviour and biochemical alterations but the combination 
      therapy demonstrated an appreciable reversal of CCI-induced changes. 
      Nitrotyrosine and Poly ADP-Ribose (PAR) immunopositivity was decreased and 
      nuclear factor erythroid 2-related factor (Nrf-2) levels were increased 
      significantly in micro-sections of the sciatic nerve and dorsal root ganglion 
      (DRG) of treatment group. These results suggest that simultaneous inhibition of 
      oxidative stress-PARP activation cascade may potentially be useful strategies for 
      management of trauma induced neuropathic pain.
CI  - Copyright A(c) 2016 Elsevier Ltd. All rights reserved.
FAU - Komirishetty, Prashanth
AU  - Komirishetty P
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER)-Hyderabad, Balanagar, India; Division of 
      Neurology, Department of Medicine, University of Alberta, 2E3.26 Walter C 
      Mackenzie, Health Sciences Center, Edmonton, AB, T6G 2B7, Canada.
FAU - Areti, Aparna
AU  - Areti A
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER)-Hyderabad, Balanagar, India.
FAU - Gogoi, Ranadeep
AU  - Gogoi R
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research (NIPER), Guwahati, India.
FAU - Sistla, Ramakrishna
AU  - Sistla R
AD  - Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad, 
      India.
FAU - Kumar, Ashutosh
AU  - Kumar A
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER)-Hyderabad, Balanagar, India. Electronic address: 
      ashutosh.niperhyd@gov.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161003
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antioxidants)
RN  - 0 (Naphthalimides)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Quinolones)
RN  - 0U46U6E8UK (NAD)
RN  - 1742-95-6 (4-amino-1,8-naphthalimide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9753I242R5 (1-Naphthylamine)
RN  - 9IKM0I5T1E (Quercetin)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - 1-Naphthylamine/administration & dosage/*analogs & derivatives/therapeutic use
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Antioxidants/*administration & dosage/therapeutic use
MH  - Encephalitis/complications/enzymology/*prevention & control
MH  - Hyperalgesia/prevention & control
MH  - Male
MH  - Mitochondria/drug effects/metabolism
MH  - NAD/metabolism
MH  - Naphthalimides/*administration & dosage/therapeutic use
MH  - Neuralgia/complications/enzymology/*prevention & control
MH  - Oxidative Stress/drug effects
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/therapeutic use
MH  - Poly(ADP-ribose) Polymerases/*metabolism
MH  - Quercetin/*administration & dosage/therapeutic use
MH  - Quinolones/*administration & dosage/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sciatic Nerve/injuries
OTO - NOTNLM
OT  - 4-ANI
OT  - Bioenergetic crisis
OT  - Chronic constriction injury
OT  - Oxidative stress
OT  - PARP
OT  - Quercetin
EDAT- 2016/11/05 06:00
MHDA- 2017/07/01 06:00
CRDT- 2016/11/05 06:00
PHST- 2016/05/01 00:00 [received]
PHST- 2016/09/04 00:00 [revised]
PHST- 2016/09/27 00:00 [accepted]
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2016/11/05 06:00 [entrez]
AID - S0028-3908(16)30437-3 [pii]
AID - 10.1016/j.neuropharm.2016.09.027 [doi]
PST - ppublish
SO  - Neuropharmacology. 2017 Feb;113(Pt A):137-147. doi: 
      10.1016/j.neuropharm.2016.09.027. Epub 2016 Oct 3.