Investigating the potential protective effects of omega-3 against doxorubicin-induced renal injury in rats through modification of antioxidant markers

Introduction: Acute kidney injury (AKI) is a severe complication in patients undergoing chemotherapy that significantly impacts their clinical outcomes and quality of life. Doxorubicin (DOX), a potent chemotherapeutic agent, is known for its wide range of adverse effects, including nephrotoxicity. Omega-3 fatty acids, known for their anti-inflammatory and antioxidant properties, have shown potential to protect against such injuries. Objectives: This study evaluated the nephroprotective effects of omega-3 fatty acids on rats with acute DOX-induced renal injury and examined the levels of associated antioxidant markers (Nrf2, HO1, GPx). Materials and Methods: Forty rats were randomized into five equal groups: Group I (control group); Group II (DOX group), which received a single dose of 15 mg/kg DOX via IP (intraperitoneal injection); and groups III, IV, and V, which received oral doses of omega-3 (100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively) for 28 days followed by a single dose of 15 mg/kg DOX via IP. After 48 hours, blood samples were collected, and the gene expression levels of Nrf2, HO1 and GPx were measured by quantitative reverse transcription polymerase chain reaction (qRT‒PCR). Results: Nrf2 expression was highly significantly lower in the DOX group (3.415 ± 0.35; P ≤ 0.001) than in the control group (28.059 ± 2.19), while the fold change was highly significantly greater in the omega-3 groups IV and V (8.692 ± 0.69, 13.645 ± 0.97; P ≤ 0.001). HO1 also exhibited a highly significant decrease in the fold change in the DOX group (1.623 ± 0.14; P ≤ 0.001) compared with the control group (34.893 ± 2.07), while it exhibited a highly significant increase in the omega-3 groups IV and V (11.423 ± 0.57 and 12.301 ± 0.64, respectively; P ≤ 0.001). GPx significantly decreased the fold change in the DOX group (0.195 ± 0.02; P ≤ 0.0017) compared with that in the control group (1.792 ± 0.28), while it significantly increased in the omega-3 groups IV and V (0.729 ± 0.08, 1.081 ± 0.11; P ≤ 0.0017). Conclusion: These results demonstrate the potential role of omega-3 in enhancing antioxidant markers, highlighting the prophylactic potential of omega-3 as a complementary treatment strategy to mitigate the nephrotoxic effects of chemotherapeutic agents such as DOX, which could improve clinical outcomes for cancer patients undergoing chemotherapy