Thymoquinone improves cognitive and hippocampal long-term potentiation deficits due to hepatic encephalopathy in rats

Objective(s): Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that causes brain disturbances. Thymoquinone (TQ) has a wide spectrum of activities such as antioxidant, anti-inflammatory, and anticancer. This study aimed to evaluate the effects of TQ on spatial memory and hippocampal long-term potentiation (LTP) in rats with thioacetamide (TAA)-induced liver injury and hepatic encephalopathy. Materials and Methods: Adult male Wistar rats were divided into six groups randomly: ۱) Control; ۲) HE, received TAA (۲۰۰ mg/kg); ۳-۵) Treated groups (HE+TQ۵, HE+TQ۱۰, and HE+TQ۲۰). TQ (۵, ۱۰, and ۲۰ mg/kg) was injected intraperitoneally (IP) for ۱۲ consecutive days from day ۱۸ to ۲۹. Subsequently, spatial memory performance was evaluated by the Morris water maze paradigm and hippocampal LTP was recorded from the dentate gyrus (DG) region. Activity levels of Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in the hippocampal tissue.Results: Data showed that the hippocampal content of MDA was increased while SOD activities were decreased in TAA-induced HE. TQ treatment significantly improved spatial memory and LTP. Moreover, TQ restored the levels of MDA and SOD activities in the hippocampal tissue in HE rats. Conclusion: Our data confirm that TQ could attenuate cognitive impairment and improve LTP deficit by modulating the oxidative stress parameters in this model of HE, which leads to impairment of spatial cognition and LTP deficit. Thus, these results suggest that TQ may be a promising agent with positive therapeutic effects against liver failure and HE defects.

Keywords:

Hepatic encephalopathy , LTP , Oxidative stress , Spatial cognition , Thioacetamide , Thymoquinone