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. Fourty adult female albino rats were randomly classified into 4 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/day colistin was given for 7 days) and the colistin and MSC treated group (36 mg/kg/day colistin was administered for 7 days, 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.