Protective effect of thymoquinone against acrylamide-induced hepatotoxicity in the rat: role of MAPK and apoptosis pathways.

Acrylamide (ACR) is widely used in industry and induces hepatotoxicity. Thymoquinone (TQ), the main constituent of the black seed (Nigella sativa L.) oil, possesses potent antioxidant and anti-apoptotic properties. The potential protective effect of TQ in ACR-induced hepatotoxicity through MAPK signaling and intrinsic/extrinsic apoptosis pathways was investigated. Animals were randomly divided into seven groups (n = 6). Control (normal saline), ACR (50 mg/kg), ACR + TQ (2.5, 5 and 10 mg/kg), ACR + vitamin E (200 mg/kg), and TQ (10 mg/kg) were administered intraperitoneally to male Wistar rats for 11 days. The content of malondialdehyde and glutathione in the liver, alanine aminotransferase, aspartate transaminase, albumin, and total serum protein were measured. Apoptosis- and mitogen-activated protein kinases (MAPK) pathway proteins in the liver were evaluated by western blotting. ACR increased AST (p < 0.001) and MDA (p < 0.01) levels and decreased GSH (p < 0.01) content in comparison to the control group. The levels of apoptosis pathway proteins (caspases 3, 8, and 9) and MAPK pathway proteins (p-p38, p-JNK, and JNK) were significantly increased in the ACR group. Co-administration of TQ (10 mg/kg) with ACR remarkably reduced AST (p < 0.01), enhanced GSH content (p < 0.001), reduced MDA level (p < 0.05), and down-regulated caspases 3, 8, and 9 (p < 0.05) and p-p38, p-JNK, and JNK proteins. ACR induces hepatotoxicity via oxidative stress and activation of MAPK and apoptosis pathways. TQ exerts a hepatoprotective effect through its antioxidant, anti-apoptotic, and MAPK-modulating properties.