Acetaminophen APAP) is a well-known analgesic, and antipyretic drug and its overdose or chronic consumption can lead to kidney damage. Oleuropein (OLE) exhibits various pharmacological properties. This study aimed to determine the possible therapeutic benefits of OLE in improving APAP-induced kidney injury. In this experimental study, 36 male Wistar rats were assigned to six groups (n = 6). The rats initially received a single dose of APAP (500 mg/kg) and then 1 hour later were treated with a single dose of OLE at 50, 100, and 200 mg/kg depending on their groups. 24 hours after treatment with OLE, various indicators including kidney biochemical tests, histopathological changes, oxidative stress markers, and anti-apoptotic and anti-inflammatory parameters were investigated in the renal tissue. OLE (100 mg/kg) significantly decreased serum creatinine, caspase-3, kidney tissue damage score ( < 0.05), malondialdehyde (MDA) ( < 0.01), and increased superoxide dismutase (SOD) and total antioxidant capacity (TAC) ( < 0.05) in the APAP + OLE 100 mg/kg group versus APAP group. Additionally, OLE (200 mg/kg) significantly reduced blood urea nitrogen (BUN), NF-κB, p53, Bax ( < 0.05), serum creatinine, TNF-α, caspase-3, kidney tissue damage score ( < 0.01), MDA, and Bax: Bcl-2 ratio ( < 0.001) in the APAP + OLE 200 mg/kg group versus APAP group. Also, OLE (200 mg/kg) significantly enhanced glutathione peroxidase (GPx), SOD, Bcl-2 ( < 0.05), and TAC ( < 0.01) in the APAP + OLE 200 mg/kg group contrasted to APAP group. However, OLE at 50 mg/kg didn't alter measured parameters. These findings demonstrate that OLE (200 mg/kg) could attenuate acetaminophen-induced kidney injury through its anti-oxidant, anti-inflammatory, and anti-apoptosis properties.
