Bone marrow-derived mesenchymal stem cells reduce CCl4-induced kidney injury and fibrosis in male Wistar rats.

Abstract

Aim: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl₄) in Wistar rats.

Methods: Following an intraperitoneal injection of CCl₄ (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 10⁶ cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.

Results: In CCl₄-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl₄-injected rats considerably reduced the previously noted abnormalities.

Conclusions: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl₄ injections.