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Imbalanced oxidative stress and pro-inflammatory markers differentiate the development of diabetic neuropathy variants in streptozotocin-induced diabetic rats

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Abstract

Purpose

Diabetic neuropathy is a prolonged symptom of diabetes mellitus that affect a number of diabetes mellitus patients. So far, the variants of diabetic neuropathy, either painful (PDN) or non-painful (or painless, non-PDN) response have distinctive clinical entities. This study aims to determine the effects of oxidative stress parameters and pro-inflammatory factors at spinal cord level of streptozotocin-induced diabetic neuropathy rat model.

Methods

Thirty Sprague-Dawley rats were randomly assigned to control (non-diabetic), PDN and non-PDN groups (n = 10). The rats were induced with diabetes by streptozotocin injection (60 mg/kg). Tactile allodynia and thermal hyperalgesia were assessed on day 0, 14 (week 2) and 21 (week 3) in the rats. The rats were sacrificed and the spinal cord tissue was collected for the measurement of oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD) and catalase) and pro-inflammatory markers (interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α)).

Results

PDN rats demonstrated a marked tactile allodynia with no thermal hyperalgesia whilst non-PDN rats exhibited a prominent hypo-responsiveness towards non-noxious stimuli and hypoalgesia towards thermal input. The MDA level and pro-inflammatory TNF-α was significantly increased in PDN rats whilst catalase was reduced in these rats. Meanwhile, non-PDN rats demonstrated reduced SOD enzyme activity and TNF-α level and increased MDA and catalase activity.

Conclusion

The changes in oxidative stress parameters and pro-inflammatory factors may contribute to the changes in behavioural responses in both PDN and non-PDN rats.

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Acknowledgements

We thanked Universiti Sains Malaysia and Ministry of Higher Education for funding of Research University Grant (RUI 1001/PPSK/812139) and Fundamental Research Grant Scheme (FRGS 203/PPSK/6171189), respectively. We thanked all Physiology Laboratory, Central Research Laboratory, Maxillo-Craniofacial Laboratory, Biological Molecular Laboratory staffs and Wan Muhammad Hilmi for direct and indirect assistance and technical work.

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Correspondence to Che Aishah Nazariah Ismail.

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Ismail, C.A.N., Aziz, C.B.A., Suppian, R. et al. Imbalanced oxidative stress and pro-inflammatory markers differentiate the development of diabetic neuropathy variants in streptozotocin-induced diabetic rats. J Diabetes Metab Disord 17, 129–136 (2018). https://doi.org/10.1007/s40200-018-0350-x

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