The neuroprotective effect of mesenchymal stem cells in colistin-induced neurotoxicity

Abstract

Colistin is an effective antibiotic against multidrug-resistant gram-negative bacterial infections; however, neurotoxic effects are fundamental dose-limiting factors for this treatment. Stem cell therapy is a promising method for treating neuronal diseases. Multipotent mesenchymal stromal cells (MSC) represent a promising source for regenerative medicine. Identification of neuroprotective agents that can be co-administered with colistin has the potential to allow the clinical application of this essential drug. This study was conducted to assess the potential protective effects of MSC, against colistin-induced neurotoxicity, and the possible mechanisms underlying any effect. Forty adult female albino rats were randomly classified into four equal groups; the control group, the MSC-treated group (A single dose of 1 × 106/mL MSCs through the tail vein), the colistin-treated group (36 mg/kg/d colistin was given for 7 d) and the colistin and MSC treated group (36 mg/kg/d colistin was administered for 7 d, and 1 × 106/mL MSCs). Colistin administration significantly increased GFAP, NGF, Beclin-1, IL-6, and TNF-α immunreactivity intensity. MSC administration in colistin-treated rats partially restored each of these markers. Histopathological changes in brain tissues were also alleviated by MSC co-treatment. Our study reveals a critical role of inflammation, autophagy, and apoptosis in colistin-induced neurotoxicity and showed that they were markedly ameliorated by MSC co-administration. Therefore, MSC could represent a promising agent for prevention of colistin-induced neurotoxicity.

Keywords:

• Colistin
• immunohistochemistry
• mesenchymal stem cells
• neurotoxicity
• oxidative stress

Acknowledgments

The authors thank Genome and Stem Cell Center (GENKOK) and Erciyes University Scientific Research Projects Unit.

Disclosure statement

The authors declared that there was no conflict of interest.

Additional information

Funding

This study protocol was supported by Erciyes University Scientific Research Projects Coordination Unit [ERÜ/BAP, Project No: TSA-2021-11331].