Pioglitazone Mitigates the Toxic Effect of Doxorubicin-Induced Nephrotoxicity

Background and Objective: Doxorubicin (DXR), a widely prescribed chemotherapeutic agent, is given to patients for the treatment of different types of cancer. The adverse effects of this substance are well-documented and can lead to harm in various organs such as the liver, kidneys, nervous system and bone marrow. A study found that pioglitazone (PIO) has demonstrated promising results in managing diabetes mellitus and Alzheimer’s disease by effectively lowering blood sugar levels and reducing neurotoxicity. The current research focuses on investigating the potential protective effect of co-treatment with PIO on nephrotoxicity induced by DXR. Materials and Methods: Forty rats weighing 230-255 g were split into four groups, with ten animals. These groups were divided into control and three therapies. Control animals received saline. The DXR animals were administered intraperitoneal four doses (5 mg/kg). The PIO-treated animals got 2 mg/mL mixed in their drinking water one day before DXR administration and continued until the last dosage. The remaining group received four DXRs and a daily PIO in drinking water. The animals were observed for mortality and blood samples were obtained to quantify BUN and creatinine. Results: It was found that the animals who received DXR had a higher mortality rate compared to the control group. In addition, the survival rate is improved when DXR and PIO are combined. In addition, there was a notable rise in the levels of BUN and creatinine, along with their ratio, in the animals that received DOX. However, this increase was reversed when PIO was combined with DXR. Conclusion: The study’s findings indicate that DXR can cause nephrotoxicity, increasing BUN and creatinine levels. However, co-treatment with PIO appears to counteract this elevation, suggesting that PIO may have a beneficial effect in reducing DXR toxicity in the kidney.