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


ÖZ GERGİN Ö., GERGİN I. Ş. , PEHLİVAN S. S. , CENGİZ MAT Ö., TURAN I. T. , BAYRAM A., ...More

TOXICOLOGY MECHANISMS AND METHODS, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/15376516.2022.2090303
  • Journal Name: TOXICOLOGY MECHANISMS AND METHODS
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Colistin, immunohistochemistry, mesenchymal stem cells, neurotoxicity, oxidative stress, MITOCHONDRIAL DYSFUNCTION, INDUCED APOPTOSIS, OXIDATIVE STRESS, BRAIN, ASTROCYTES, MARROW, METHANESULFONATE, NEPHROTOXICITY, SUPPRESSION, EXPRESSION

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 x 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 x 106/mL MSCs). Colistin administration significantly increased GFAP, NGF, Beclin-1, IL-6, and TNF-alpha 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.