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Background & Objective:Acetaminophen is known as the most common agent which causes hepatic and renal toxicity in human and experimental animals at supra-therapeutic doses. The current study investigated the protective effects ofDescurainia sophiaseed extract on the acetaminophen-induced nephrotoxicity markers in male mice. Materials & Methods:Experimental male mice (n=60, Swiss albino mice) were divided into six groups as follows: Group A (control group), Group B (acetaminophen group), and treatment groups including T1, T2, T3, and T4 (D. sophiaseed extract groups). Toxicity was induced by acetaminophen (500 mg/kg). The mice administeredD. sophiaseed extract for 7 days in doses of 50, 100, 200, and 300 mg/kg. In the next step, animals were euthanized 24 hours after acetaminophen administration. Blood samples were collected. Serum levels of blood urea nitrogen (BUN), creatinine, and uric acid were analysed. Furthermore, kidney tissues were removed for histopathological examination via haematoxylin and eosin staining. Results:Our data revealed that acetaminophen increased the levels of BUN, creatinine and uric acid (PD. sophiaseed extract decreased the serum BUN, creatinine and uric acid significantly compared to the acetaminophen group (PD. sophiaextract had restored acetaminophen-induced nephrotoxicity, particularly in the dose of 300 mg/kg. Conclusion:The present findings suggested that oral administration of D. sophia seed extract has protective effect against acetaminophen nephrotoxicity in mice. Keywords:Acetaminophen,BUN,Creatinine,Descurainia sophia seed,Mice,Nephrotoxicity