Differential and Combined Therapeutic Effects of Mesenchymal Stem Cells and Glutathione on Methotrexate-Induced Mucositis
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.40, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 40 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jbt.71023
- Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Erciyes Üniversitesi Adresli: Evet
Özet
Methotrexate (MTX) is commonly used in chemotherapy but induces severe side effects, such as intestinal mucositis, which is characterized by oxidative stress, inflammation, and epithelial cell death. Mesenchymal stem cells (MSCs) and glutathione (GSH) are potential therapeutic agents that could alleviate these effects. In this study, 30 adult female Wistar-Albino rats were assigned to five groups (n = 6) and received either an intraperitoneal dose of MTX (45 mg/kg) followed by treatments of MSCs, GSH, or a combination. MSCs were isolated and confirmed for multipotent differentiation capabilities. The effects of the treatments were assessed through histopathological analysis, immunohistochemistry, biochemical analyses, and gene expression using RT-qPCR. The MTX group showed significant mucosal damage, including villus atrophy, epithelial shedding, and increased fibrosis. However, treatment groups demonstrated partial preservation of villus architecture and reduced histopathological damage compared with the MTX group. MTX administration also markedly increased inflammatory and apoptotic markers, including TNF-alpha, IL-1 beta, and caspase-3, whereas these elevations were reduced to varying extents following MSC and/or GSH treatment. Additionally, MTX elevated malondialdehyde (MDA) levels and decreased antioxidant enzyme activities, MSC and/or GSH treatments attenuated oxidative stress and improved antioxidant parameters. In conclusion, the combination of MSCs and GSH treatment attenuated MTX-induced intestinal injury through reduction of oxidative stress, inflammation and apoptosis and enhancement of mucosal recovery. The findings suggest that MSC and GSH may exert complementary protective effects against MTX-induced intestinal toxicity; however, definitive superiority of the combined treatment over monotherapies was not consistently supported by the statistical analyses. However, further studies with larger sample sizes and mechanistic studies are needed to elucidate the underlying interactions and to confirm translational applicability.