Nonylphenol (NP), a well-known endocrine-disrupter chemical, has several harmful effects on the central nervous system including neuroendocrine disruption,
cognitive impairment, and neurotoxicity.
Thymoquinone (TQ) is a main bioactive compound in the black seeds of Nigella sativa that has
antioxidant, anti-inflammatory, and neuroprotective properties. Here, we investigated the
neuroprotective effect of TQ against NP-induced
memory deficit and neurotoxicity in rats. To induce memory impairment, NP (25 mg/kg) was used as gavage in male Wistar rats for 21 days. TQ (2.5, 5, and 10 mg/kg) was intraperitoneally administered in NP-treated animals. The morris water maze test was performed to assess spatial learning and memory. The hippocampal tissues were isolated from the brain for histopathological evaluation. Biochemical, molecular, and cellular tests were performed to quantify
oxidant (
malondialdehyde; MDA)/
antioxidant (
superoxide dismutase (SOD), total
antioxidant capacity (TAC), and
reduced glutathione (GSH) parameters) as well as markers for astrocytic activation (
glial fibrillary acidic protein; GFAP) and neuronal death (
alpha-synuclein; α-syn). Results showed TQ (5 mg/kg) significantly improved NP-induced memory impairment. Histological data revealed a significant increase in the number of necrotic cells in hippocampus, and TQ treatment markedly decreased this effect. The GSH and TAC levels were significantly increased in TQ-treated groups compared to NP group. The molecular analysis indicated that NP increased GFAP and decreased α-syn expression and TQ treatment did the reverse. In vitro study in astrocytes isolated from mice brain showed that TQ significantly increased cell viability in NP-induced cytotoxicity. This study strongly indicates that TQ has
neuroprotective effects on NP-induced neurotoxicity through reducing oxidative damages and
neuroinflammation. This study investigates the behavioral neurotoxicity induced by
Nonylphenol (NP) and the protective effects of
Thymoquinone (TQ) as a potent
antioxidant compound using molecular, cell culture, histopathological and biochemical techniques.