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Published yearly: 

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ISSN: 2320-964X (Online) 

ISSN: 2320-7817  (Print)



Dr. Santosh Pawar 




Int. Journal of Life Sciences, 2018; 6(1): 29-40       |                 Available online, February 24, 2018

Minocycline and Ifenprodil Prevent Development of Painful Diabetic Neuropathy in Streptozotocin-induced Diabetic Rat Model

Che Aishah Nazariah Ismail1 3*, Suppian Rapeah2,Abd Aziz Che Badariah3 and  Long Idris1 2


1BRAINetwork Centre for Neurocognitive Sciences, School of Health Sciences, 2 School of Health Sciences, 3Department of Physiology, School of Medical Science, Universiti Sains Malaysia Heath Campus, 16150 Kubang Kerian, Kelantan, Malaysia

*Correspondence: Tel: +60199722559, Email:


Received : 20.12.2017    |    Accepted : 29.01.2018    |   Published : 24.02.2018

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus which hugely affect life routines and quality. We aimed to investigate the effects of minocycline and ifenprodil on nociceptive behavior response, oxidant-antioxidant status and pro-inflammatory markers level in the PDN rat’s spinal cord. Forty-eight male Sprague-Dawley rats were divided into six groups (n=8): non-diabetic control, diabetic PDN control, diabetic PDN rats received minocycline (80µg/day or 160µg/day) and diabetic PDN rats received ifenprodil (0.5µg/day or 1.0µg/day). Diabetes was induced by single injection of streptozotocin at 60mg/kg. The rats were allowed for two weeks period to develop into PDN condition. The intrathecal treatments were given for seven days period. The rat’s hind paw was then injected with 5% formalin to induce chronic inflammatory pain and sacrificed three days post-formalin injection. Spinal cord tissue was removed and homogenized (10% homogenate). ELISA for oxidant-antioxidant markers (MDA, catalase and SOD) and pro-inflammatory markers (TNF-α and IL-1β) were carried out. The results showed that untreated PDN rats exhibited increased nociceptive behavior responses indicating hyperalgesia apart from increased MDA activity, reduced catalase with insignificant change in SOD enzymes activities, increased TNF-α and insignificant change in IL-1β level. Minocycline and ifenprodil suppressed MDA activity and improved catalase and SOD activities. Minocycline attenuated both pro-inflammatory cytokines whilst ifenprodil reduced TNF-α level but increased IL-1β level. In conclusion, minocycline and ifenprodil showed potent anti-nociceptive, anti-oxidant and anti-inflammatory effects but possibly via different pathway and mechanism.


Keywords: Painful diabetic neuropathy, minocycline, ifenprodil, formalin test, catalase, interleukin-1β, malondialdehyde, superoxide dismutase, tumour necrosis factor-α


Editor: Dr.Arvind Chavhan


Cite this article as:

Che Aishah Nazariah Ismail, Suppian Rapeah,Abd Aziz Che Badariah and  Long Idris (2018) Minocycline and Ifenprodil Prevent Development of Painful Diabetic Neuropathy in Streptozotocin-induced Diabetic Rat Model, Int. J. of. Life Sciences, Volume 6(1): 29-40. 


Conflicts of interest: The authors stated that no conflicts of interest.



Copyright: © 2018 | Author(s), This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial - No Derives License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.



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