The Protective Effects of Mitochondrial Therapy Against Vincristine- Induced Nephrotoxicity in the Rat’s Renal Proximal Tubular Cells
| Author | Armaghan Lohrasbi |
| Author | Abdollah Arjmand |
| Author | Farzaneh Kamranfar |
| Author | Mehdi Aghsami |
| Author | Jalal Pourahmad |
| Issued Date | 2025-12-31 |
| Abstract | Background: The application of vincristine (VCR) in treating a range of cancers is well-documented, showcasing its considerable effectiveness. Nevertheless, its clinical application is constrained by its impact on healthy tissues and various organ systems. Specifically, it can compromise kidney function, resulting in toxicological concerns. Studies have demonstrated that vincristine contributes to nephrotoxicity via the induction of oxidative stress. Objectives: The present research focused on assessing the influence of mitochondrial transplantation in mitigating the mitochondrial and cellular toxicity associated with VCR in renal proximal tubular cells (RPTCs). Methods: This investigation evaluated specific toxicity metrics, including cell death, reactive oxygen species (ROS) generation, decreased mitochondrial membrane potential (MMP), glutathione (GSH) concentration, succinate dehydrogenase (SDH) activity, lipid peroxidation (LPO), and adenosine triphosphate (ATP) levels. Freshly prepared active mitochondria were obtained from the kidneys of Wistar rats. Results: The data demonstrated the cytotoxic effects of VCR on RPTCs. It was further observed that vincristine triggered oxidative stress, characterized by heightened ROS levels, diminished GSH content, decreased SDH activity, and increased lipid peroxidation. Furthermore, VCR caused notable damage to both mitochondrial and lysosomal membranes, along with a significant decrease in ATP content. The innovative strategy of mitochondrial transplantation mitigated oxidative stress, alleviated mitochondrial membrane damage, and prevented ROS-mediated apoptosis signaling induced by vincristine in RPTCs. Our results also indicated an increase in ATP levels within these cells. Conclusions: Our investigation suggests that the proposed treatment modality may prove beneficial in addressing drug-induced nephrotoxicity. |
| DOI | https://doi.org/10.5812/ijpr-159628 |
| Keyword | Vincristine |
| Keyword | Oxidative Stress |
| Keyword | Nephrotoxicity |
| Keyword | Mitochondria Transplantation |
| Keyword | Renal Proximal Tubular Cells |
| Publisher | Brieflands |
| Title | The Protective Effects of Mitochondrial Therapy Against Vincristine- Induced Nephrotoxicity in the Rat’s Renal Proximal Tubular Cells |
| Type | Research Article |