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Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats

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Abstract

In this study, we hypothesized that reduction of immune cell activation as well as their oxidant or inflammatory mediators with minocycline (MCN), liposome-encapsulated clodronate (LEC), or anti-Ly6G treatments can be neuroprotective approaches in diabetic neuropathy. MCN (40 mg/kg) for reduction of microglial activation, LEC (25 mg/kg) for of macrophage inhibition, or anti-Ly6G (150 μg/kg) for neutrophil suppression injected to streptozotocin (STZ)-induced diabetic rats twice, 3 days, and 1 week (half dose) after STZ. Animal mass and blood glucose levels were measured; thermal and mechanical sensitivities were tested for in pain sensations. The levels of chemokine C-X-C motif ligand 1 (CXCL1), CXCL8, and C-C motif ligand 2 (CCL2), CCL3, and total oxidant status (TOS) and total antioxidant status (TAS) were measured in the spinal cord and sciatic nerve tissues of rats. LEC significantly reduced the glucose level of diabetic rats compared with drug control. However, MCN or anti-LY6G did not change the glucose level. While diabetic rats showed a marked decrease in both thermal and mechanical sensations, all treatments alleviated these abnormal sensations. The levels of chemokines and oxidative stress parameters increased in diabetic rats. All drug treatments significantly decreased the CCL2, CXCL1, and CXCL8 levels of spinal cord tissues and ameliorated the neuronal oxidative stress compared with control treatments. Present findings suggest that the neuroprotective actions of MCN, LEC, or anti-Ly6G treatments may be due to the modulation of neuronal oxidative stress and/or inflammatory mediators of immune cells in diabetic rats with neuropathy.

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Funding

This project was supported by The Scientific and Technological Research Council of Turkey and supported the current studies with a project number 116S502.

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Authors and Affiliations

  1. Department of Biophysics, Faculty of Medicine, Bolu Abant Izzet Baysal University, 14030, Bolu, Turkey

    Tufan Mert

  2. Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Emel Sahin & Mehmet Sahin

  3. Department of Biophysics, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

    Selma Yaman

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  1. Tufan Mert
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  2. Emel Sahin
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  3. Selma Yaman
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  4. Mehmet Sahin
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Contributions

TM wrote the article, and ES and MS revised it. TM and SY designed the project studies. TM and SY collected the metabolic and behavioral data and did the analyses. ES and MS collected and analyzed the biochemical data.

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Correspondence to Tufan Mert.

Ethics declarations

In this present study, the experimental protocols were approved by the animal research committee of Kahramanmaras Sutcu Imam University (03–04/2016). All experiments were accomplished in accordance with the guidelines of International Association for the Study of Pain (IASP) Committee for Research and Ethical Issues.

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The authors declare that they have no conflicts of interest.

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Mert, T., Sahin, E., Yaman, S. et al. Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1293–1302 (2020). https://doi.org/10.1007/s00210-020-01871-9

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  • DOI: https://doi.org/10.1007/s00210-020-01871-9

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