Nesfatin-1 Exerts a Neuroprotective Effect in Thioacetamide-Induced Acute Hepatic Encephalopathy by Activating the...

Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with liver failure. Nesfatin-1 is a neuropeptide characterized by its antioxidant and anti-inflammatory properties.

This study aimed to evaluate the neuroprotective and hepatoprotective effects of nesfatin-1 in a thioacetamide (TAA)-induced rat model of acute HE. Additionally, the study aimed to examine the underlying mechanisms, particularly the role of the PI3K/Akt/Nrf2/HO-1 signaling pathway.

Male Sprague Dawley rats were divided into five groups: (1) untreated control, (2) nesfatin-1-treated control, (3) thioacetamide-induced hepatic encephalopathy (HE), (4) HE + nesfatin-1, and (5) HE + nesfatin-1 + zinc protoporphyrin IX (ZnPP IX; HO-1 inhibitor). Assessments included behavioral analysis, serum liver function biomarkers, oxidative stress and inflammatory markers, brain water content, mRNA expression of HO-1 (Heme Oxygenase 1) and GFAP (Glial Fibrillary Acidic Protein), PI3K/Akt/Nrf2 protein levels, as well as histological and immunohistochemical evaluations.

Nesfatin-1 significantly improved psychomotor activity, reduced serum ALT, AST, total bilirubin, and ammonia levels, and increased albumin. It also lowered brain MDA, TNF-α, IL-6, and CRP levels, reduced brain water content, and upregulated the expression of HO-1 and GFAP. Furthermore, nesfatin-1 activated the PI3K/Akt/Nrf2 pathway and inhibited the expression of caspase-3 and NF-κB in liver and brain tissues. These protective effects were negated by HO-1 inhibition using ZnppIX. Histological analysis demonstrated the structural integrity of liver and brain tissues in rats treated with nesfatin-1.

Nesfatin-1 exerts potent hepatoprotective and neuroprotective effects in TAA-induced hepatic encephalopathy via antioxidative, anti-inflammatory, and antiapoptotic mechanisms involving the PI3K/Akt/Nrf2/HO-1 pathway.