Effect of Bone Marrow and Adipose Mesenchymal Stem Cells On Rat Intestinal Injury Induced By Methotrexate - Effect of Bone Marrow and Adipose Mesenchymal Stem Cells On Rat Intestinal Injury Induced By Methotrexate - Open Access Pub

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury. DOI10.14302/issn.2640-6403.jtrr-18-2449 Methotrexate (MTX) is an antagonist of folic acid 1. MTX competitively inhibits the dihydrofolate reductase (DHFR) enzyme, which participates in the synthesis of folic acid and inhibits conversion of dihydrofolate to tetrahydrofolate. Subsequently, DHFR is essential for biosynthesis of thymidine and purines, which are needed for synthesis of DNA. Blockade of tetrahydrofolate synthesis by MTX leads to inability of cells to divide and to produce proteins 2. Subsequently, MTX is used as an antimetabolite in cancer chemotherapy in the treatment of lymphocytic leukemia, non-hodgkin’s lymphoma, osteosarcoma, head neck cancer, and mammary gland tumors 3. Moreover, MTX is also intervened for rheumatoid arthritis and refractory inflammatory disease treatments 4. Nevertheless, MTX is restrained by its toxicity, including intestinal injury causes severe mucositis 5, enterocolitis, cardiotoxicity, nephrotoxicity and hepatotoxicity. Mucositis involves inflammation and mucosal ulceration of the alimentary tract, resulting in symptoms including pain, abdominal bloating, nausea, vomiting diarrhea and weight loss and disrupted chemotherapy 6, 7. In addition, chemotherapy may exert cell damaging or a cell-destroying effect through the generation of reactive oxygen species, or through enzymatic or transcription factors (NF-？B) which leads to up regulation of genes