Minocycline reduces proinflammatory and oxidative stress markers in the spinal cord and morphology changes in sciatic nerve of Type 2 diabetic neuropathy rat model

Abstract

Aim: Diabetic neuropathy (DN) is a consequence of prolonged hyperglycemia due to inflammation process in nerve. Minocycline has been shown to act as anti-inflammatory agent but their effects on Type 2 diabetic (T2DM) neuropathy rats’ model are still unclear. This study investigated the effects of minocycline on proinflammatory cytokines and oxidative stress marker levels in the spinal cord and sciatic nerve morphology in T2DM neuropathy rats. Methods: Male Sprague Dawley rats were randomly assigned to six groups (n=14 per groups): Control (C), T2DM control (STZ), T2DM treated with minocycline 40 mg/kg (STZ+ M40) and 80 mg/kg (STZ + M80), T2DM treated with gabapentin (STZ + G10) and non-painful T2DM neuropathy (NPDN). T2DM was induced in obese rats using a combination of high fat diet (HFD) and low dose streptozotocin (STZ) (40 mg/kg) injection. Then, the neuropathic pain behaviour, body weight and blood biochemical analysis were performed. Rats were sacrificed and the spinal cord and sciatic nerve were collected for ELISA and histology examination. Results: After 6 weeks treatment with HFD diet, all T2DM rat groups were significantly increased body weight but significantly reduced from 8 until 9 weeks after STZ were injected compared to control group (p<0.05). The fasting blood glucose (FBG) level in all T2DM groups were significantly higher on day 3, day 14, and day 22 of the study compared to control group (p<0.05) consistent with HbA1c levels. T2DM groups also significantly increased MDA, TNF-α, IL-1β and C-Reactive Protein (CRP) but decreased SOD and Catalase levels in the spinal cord compared to control group (p<0.05). T2DM groups also showed significant abnormal histopathological changes in the sciatic nerve compared to control group (p<0.05). Administration of minocycline dependent on doses and gabapentin in T2DM rat significantly alleviated all these effects. Conclusion: Dependent on dose, minocycline was found to reduce pro-inflammatory cytokines and oxidative stress markers level in the spinal cord and recovery sciatic nerve morphology changes of T2DM neuropathy rats. These findings suggest the neuroprotective effects of minocycline on T2DM neuropathy.