The underlying mechanisms of bisphenol A (BPA)‐induced metabolic disorder and the protective impact of Nigella sativa oil (NSO) and thymoquinone (TQ) against BPA‐induced metabolic disorder were investigated. Rats were treated as follows: Control, BPA (10 mg/kg), TQ (2 mg/kg), NSO (84 μL/kg), BPA + TQ (0.5, 1, 2 mg/kg), and BPA + NSO (21, 42, 84 μL/kg). BPA was administered by gavage, while, TQ and NSO were injected intraperitoneally (daily, 54 days). The weight, blood pressure, serum parameters [glucose, lipid profile, hepatic enzymes, insulin, interlukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), leptin, adiponectin], malondialdehyde (MDA), glutathione (GSH) and insulin signaling pathways [insulin receptor substrate (p‐IRS,IRS); kinase (p‐Akt,Akt); glycogen synthase kinase (p‐GS3K,GS3K)] were measured. BPA increased the blood pressure, MDA, lipid profile, hepatic enzymes, insulin, IL‐6, TNF‐α, and leptin, and decreased the GSH and phosphorylated forms of IRS, Akt, GS3K but did not alter weight, glucose, IRS, AKT, and GS3K in the liver. Administration of NSO or TQ with BPA reduced the blood pressure, liver level of MDA, lipid profile, hepatic enzymes, insulin, IL‐6, TNF‐α, leptin, and increased the liver level of GSH and p‐IRS, p‐AKT, p‐GS3K. TQ and NSO are thought to be effective in controlling metabolic disorders induced by BPA.
