PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy Prashanth Komirishetty, Aparna Areti, Veera Ganesh Yerra, Ruby PK, Shyam S. Sharma, Ranadeep Gogoi, Ramakrishna Sistla, Ashutosh Kumar PII: DOI: Reference:
S0024-3205(16)30135-7 doi: 10.1016/j.lfs.2016.02.085 LFS 14770
To appear in:
Life Sciences
Received date: Revised date: Accepted date:
12 October 2015 12 February 2016 23 February 2016
Please cite this article as: Komirishetty Prashanth, Areti Aparna, Yerra Veera Ganesh, PK Ruby, Sharma Shyam S., Gogoi Ranadeep, Sistla Ramakrishna, Kumar Ashutosh, PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy, Life Sciences (2016), doi: 10.1016/j.lfs.2016.02.085
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy
PT
Prashanth Komirishetty, MS Pharm1, Aparna Areti, MS Pharm1, Veera Ganesh Yerra, MS Pharm1, Ruby PK, MS Pharm2, Shyam S Sharma, PhD2, Ranadeep Gogoi, PhD3, Ramakrishna Sistla, PhD4, Ashutosh Kumar, PhD1,* 1
RI
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, India. 2
SC
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India. 3
NU
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India. 4
AC CE P
*Corresponding author:
TE
D
MA
Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad, India
Dr. Ashutosh Kumar, Assistant Professor,
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar,
Hyderabad, Telangana-500037,
Tel: +91 40-23073741, Fax: +91 40-23073751, E-mail: [email protected], [email protected]
Running Title: Role of PARP in injury induced peripheral neuropathy.
Disclosure: Supported by National Institute of Pharmaceutical Education and Research, Hyderabad and Department of Biotechnology Govt of India, via grant BT/527/NE/TBP/2013 Conflict of Interest: Authors declare no conflict of Interest
1
ACCEPTED MANUSCRIPT Abstract Aim: Peripheral nerve degeneration after nerve injury is accompanied with oxidative stress that may activate poly ADP-ribose polymerase (PARP, DNA repair enzyme). PARP overactivation
PT
amplifies the neuronal damage either due to energy crisis or through an inflammatory process by
RI
facilitating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hence the aim
SC
of current study is to investigate the role of PARP inhibitors 3-Aminobenzamide (3-AB) and 1,5isoquinolinediol (ISO) in the attenuation of chronic constriction injury (CCI) induced peripheral
NU
neuropathy in rats.
MA
Methods: 3-AB and ISO (at doses 30 and 3 mg/kg i.p, respectively) were tested in rats subjected to standard tests for evaluating hyperalgesia and allodynia. Sciatic functional index (SFI) was assessed
D
by performing walking track analysis. Oxidative stress and inflammation induced biochemical
TE
alterations were estimated after 14 days in sciatic nerve and lumbar spinal cord. Molecular changes were explored by immunohistochemistry and TUNEL assay.
AC CE P
Key findings: Treatment significantly improved sensorimotor responses (p
S0024-3205(16)30135-7 doi: 10.1016/j.lfs.2016.02.085 LFS 14770
To appear in:
Life Sciences
Received date: Revised date: Accepted date:
12 October 2015 12 February 2016 23 February 2016
Please cite this article as: Komirishetty Prashanth, Areti Aparna, Yerra Veera Ganesh, PK Ruby, Sharma Shyam S., Gogoi Ranadeep, Sistla Ramakrishna, Kumar Ashutosh, PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy, Life Sciences (2016), doi: 10.1016/j.lfs.2016.02.085
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT PARP inhibition attenuates neuroinflammation and oxidative stress in chronic constriction injury induced peripheral neuropathy
PT
Prashanth Komirishetty, MS Pharm1, Aparna Areti, MS Pharm1, Veera Ganesh Yerra, MS Pharm1, Ruby PK, MS Pharm2, Shyam S Sharma, PhD2, Ranadeep Gogoi, PhD3, Ramakrishna Sistla, PhD4, Ashutosh Kumar, PhD1,* 1
RI
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Bala Nagar, India. 2
SC
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India. 3
NU
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India. 4
AC CE P
*Corresponding author:
TE
D
MA
Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad, India
Dr. Ashutosh Kumar, Assistant Professor,
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar,
Hyderabad, Telangana-500037,
Tel: +91 40-23073741, Fax: +91 40-23073751, E-mail: [email protected], [email protected]
Running Title: Role of PARP in injury induced peripheral neuropathy.
Disclosure: Supported by National Institute of Pharmaceutical Education and Research, Hyderabad and Department of Biotechnology Govt of India, via grant BT/527/NE/TBP/2013 Conflict of Interest: Authors declare no conflict of Interest
1
ACCEPTED MANUSCRIPT Abstract Aim: Peripheral nerve degeneration after nerve injury is accompanied with oxidative stress that may activate poly ADP-ribose polymerase (PARP, DNA repair enzyme). PARP overactivation
PT
amplifies the neuronal damage either due to energy crisis or through an inflammatory process by
RI
facilitating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hence the aim
SC
of current study is to investigate the role of PARP inhibitors 3-Aminobenzamide (3-AB) and 1,5isoquinolinediol (ISO) in the attenuation of chronic constriction injury (CCI) induced peripheral
NU
neuropathy in rats.
MA
Methods: 3-AB and ISO (at doses 30 and 3 mg/kg i.p, respectively) were tested in rats subjected to standard tests for evaluating hyperalgesia and allodynia. Sciatic functional index (SFI) was assessed
D
by performing walking track analysis. Oxidative stress and inflammation induced biochemical
TE
alterations were estimated after 14 days in sciatic nerve and lumbar spinal cord. Molecular changes were explored by immunohistochemistry and TUNEL assay.
AC CE P
Key findings: Treatment significantly improved sensorimotor responses (p
