Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Trough its Antioxidant and Neuroprotective Effects

Abstract Nonylphenol (NP) as a well-known endocrine-disrupter chemical (EDCs), has several harmful effects on the CNS such as neuroendocrine disruption, cognitive impairment, and neurotoxicity. Thymoquinone (TQ) is a main bioactive compound in the black seeds of nigella sativa (NS) possesses antioxidant, anti-inflammatory, and neuroprotective properties. This study was designed to assess the neuroprotective effect of TQ against NP-induced memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25mg/kg) was used as gavage in male Wistar rats for 21 days. TQ i.p. injection at doses 2.5, 5, and 10mg/kg was done in NP-treated animals at the same time. Morris Water Maze (MWM) test was performed to assess spatial memory. The rats` hippocampus tissues were isolated for histopathological testes. Biochemical, molecular and cellular tests were done for proving more details. The results showed TQ at dose 5 mg/kg significantly improved NP-induced memory impairment. Histological data proved that TQ decreased the number of necrotic cells in the hippocampus which was increased in NP-treated animals. Biochemical analysis showed that the levels of glutathione (GSH) and total antioxidant capacity (TAC) were significantly increased in TQ treated groups compared to the NP group. The molecular analysis has shown that NP increased GFAP and decreased α-Syn expression level and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain proved that TQ significantly increased cell viability in cytotoxicity induced by NP. This study strongly indicates that TQ has therapeutic and neuroprotective effects on NP-induced neurotoxicity through reduction of oxidative damages and neuroinflammation.