Nesfatin-1 Exerts a Neuroprotective Effect in Thioacetamide-Induced Acute Hepatic Encephalopathy by Activating the PI3K/Akt/Nrf2 Pathway

Abstract

<title>Abstract</title> Nesfatin-1 possesses antioxidative and antiapoptotic properties. It can protect against subarachnoid hemorrhage and brain-induced injury by reducing the activation of the pro-apoptotic protein caspase-3 and the levels of oxidative brain injury indicators. We aimed to investigate the protective effect of nesfatin-1 on the acute hepatic encephalopathy (HE) model in rats. The rats were assigned to five groups in the following manner: The Control Group received only saline. The Nesfatin-1 Control Group received both nesfatin-1 and saline. The HE Group received the vehicle and thioacetamide to induce HE. The HE + Nesfatin-1 Group received both nesfatin-1 and thioacetamide. The HE + Nesfatin-1 + heme oxygenase-1 (HO-1) Inhibitor Group received nesfatin-1, thioacetamide, and the HO-1 inhibitor ZnppIX. Psychomotor activity in rats was assessed. The levels of HO-1 and fibrillary acidic protein (GFAP) were quantitatively measured. In addition, histological examinations were conducted. Nesfatin-1 resulted in a significant improvement in psychomotor activity, a decline in brain edema, and a decrease in inflammatory and oxidative stress markers. Furthermore, it led to the activation of phosphatidylinositol 3 kinase/ protein kinase B/nuclear factor erythroid 2–related factor 2 pathways, upregulated HO-1 and GFAP expressions, and improved HE-induced structural damage in the liver and brain. Furthermore, there was a decrease in caspase-3 expression in the liver and brain, as well as a decline in nuclear factor-κB/p65 expression in brain tissue. In summary, nesfatin-1 is considered a promising drug that can be used as a neuroprotective in HE due to its anti-inflammatory, antioxidative, and antiapoptotic effects.