3-AMINOBENZAMIDE, A POLY (ADP-RIBOSE) POLYMERASE INHIBITOR, RESTORES BIOENERGETICS BUT FAILS TO ALLEVIATE EXCITOTOXICITY AND MOTOR FUNCTIONS IN 3-NITROPROPIONIC ACID INTOXICATED MICE


Vijayan Ranju, Sekar Sathiya, Ramakrishnan Ganapathy, Gayathri Veeraraghavan, Chidambaram Saravana Babu

Abstract


Objective: The present study was undertaken to investigate the effects of 3-aminobenzamide (3-AB), a poly (ADP-ribose) polymerase 1 (PARP1) inhibitor, on motor functions along with brain excito toxicity and bioenergetics alterations in 3-nitropropionic acid (3-NPA) intoxicated mice model of Huntington’s disease (HD).

Methods: Young healthy male C57BL/6J mice were pre-treated with vehicle/3-AB for a period of five days and intoxicated with two doses of 3-NPA (15 mg/kg, i. p) at 24 h interval on day 4 and 5. Animals were observed for motor functions 5 days after 3-NPA injection. They were sacrificed at the end of motor tests and brains were collected for neurochemical, bioenergetics, glial cells and cytokines analysis.

Results: 3-AB treatment significantly increased the bioenergetics (ATP and NAD) and succinate dehydrogenase activity in 3-NPA intoxicated mice brains. But, it failed to decrease glutamate content, cytokines-TNFα and IL-1β and glial markers–glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) expressions. Further, 3-AB administered produced only a non-significant restoration of motor functions in 3-NPA intoxicated mice.

Conclusion: The present study revealed that excito toxicity and inflammatory pathways are major perpetrators in 3-NPA induced neuro degeneration and motor dysfunction. Therapeutic approach with 3-AB alone may not be sufficient to manage the multi-cascade pathogenetic mechanisms in HD neither symptomatic management too.


 


Keywords


3-aminobenzamide, 3-nitropropionic acid, Excitotoxicity, Succinate dehydrogenase, Bioenergetics, Huntington’s disease

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About this article

Title

3-AMINOBENZAMIDE, A POLY (ADP-RIBOSE) POLYMERASE INHIBITOR, RESTORES BIOENERGETICS BUT FAILS TO ALLEVIATE EXCITOTOXICITY AND MOTOR FUNCTIONS IN 3-NITROPROPIONIC ACID INTOXICATED MICE

Keywords

3-aminobenzamide, 3-nitropropionic acid, Excitotoxicity, Succinate dehydrogenase, Bioenergetics, Huntington’s disease

Date

15-06-2015

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 7, Issue 8, 2015 Page: 121-126

Online ISSN

0975-1491

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150 Views | 191 Downloads

Authors & Affiliations

Vijayan Ranju
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, TN, India
India

Sekar Sathiya
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, TN, India, Department of Biotechnology, Dr. M. G. R. Educational and Research Institute University, Chennai 600095, TN, India
India

Ramakrishnan Ganapathy
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, TN, India
India

Gayathri Veeraraghavan
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, TN, India
India

Chidambaram Saravana Babu
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, TN, India
India


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