Effects of Ertugliflozin and Lycopene on Ifosfamide-Induced Nephrotoxicity in Rats

Background: Nephrotoxicity induced by chemotherapy is a common side effect of many anticancer drugs. Objective: To evaluate the effect of ertugliflozin (ERTU) and lycopene (LYCO) against ifosfamide (IFO)-induced nephrotoxicity. Methods: 56 rats were divided into eight groups: negative control (NC), positive control (PC), control vehicle (CV), ERTU: ertugliflozin 20mg/kg, LYCO: lycopene 30mg/kg, IFO+ERTU, IFO+LYCO and IFO+ERTU+LYCO. On the 12th, 13th, and 14th days of the experiment, IFO 50 mg/kg was injected into PC, IFO+ERTU, IFO+LYCO, and IFO+ERTU+LYCO rats. Urine was collected for urinalysis. Blood and kidney tissue were harvested for oxidative stress, CBC-inflammatory and kidney injury biomarkers, and histopathological assessment. Results: IFO resulted in hematuria and proteinuria, elevation of cystatin C, kidney injury molecule-1 (KIM-1) in kidney tissue, and a reduction in total antioxidant capacity (TAC). Platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), and hemoglobin-to-lymphocyte ratio (HLR) increased significantly with histopathological alteration in kidney tissue. IFO+ERTU and IFO+ERTU+LYCO groups showed alleviation in the hematuria, proteinuria, and cystatin C. KIM-1 was significantly reduced in IFO+ERTU and non-significantly in IFO+LYCO and its combination. IFO+ERTU, IFO+LYCO, and IFO+ERTU+LYCO groups showed elevation in TAC. In IFO-exposed animals, ERTU resulted in a significant reduction in PLR and HLR and PMR non-significantly, and LYCO+ERTU significantly reduced PLR. Conclusions: ERTU and LYCO alone and in combination alleviated kidney injury parameters and the histopathological lesions. These findings suggest that ERTU and LYCO are effective nephroprotective agents against IFO-induced nephrotoxicity. The suggested mechanisms are attributed to their antioxidant and anti-inflammatory actions for both diuretic and natriuretic properties for ERTU.