# Amarogentin relieves cholestatic liver injury caused by ANIT in rats by regulating the FXR and Nrf2 pathways

## TL;DR

Amarogentin helps protect rat livers from cholestasis by improving bile flow and reducing liver damage through specific pathways.

## Contribution

Amarogentin is shown to alleviate cholestatic liver injury via FXR and Nrf2 pathways in a rat model.

## Key findings

- Amarogentin reduced liver enzyme levels and improved bile flow in cholestatic rats.
- Amarogentin suppressed oxidative stress and enhanced liver histology.
- Amarogentin activated the PI3K/Akt/Nrf2 pathway and regulated bile acid metabolism.

## Abstract

Cholestasis, a hepatic disorder characterized by impaired bile secretion, drives progressive liver damage, fibrosis, failure, and even death. This study explores how amarogentin (AG) ameliorates cholestatic liver injury in rats induced by α-naphthylisothiocyanate (ANIT).

The bile flow rate, a visual indicator of the degree of intrahepatic cholestasis, was measured to assess the model’s success. Liver function was evaluated by analyzing the serum levels of enzymes (ALP, ALT, AST, TBIL, DBIL, and TBA), as well as indicators of oxidative damage (SOD, MDA, and GSH-Px), in the liver tissue, and by examining liver histopathology. Additionally, Western blot analysis was utilized to assess the protein levels of the FXR and Nrf2 signaling pathways in the liver tissue of cholestatic rats both before and after AG treatment, to understand the underlying protective mechanism.

AG was administered intragastrically to ANIT-treated cholestatic rats, which significantly decreased the plasma concentrations of AST, ALT, ALP, TBIL, DBIL, and TBA, and alleviated ANIT-induced liver injury. AG could also significantly improve the bile flow rate and suppress oxidative stress. Western blot analysis revealed that AG could enhance ANIT-induced cholestasis by modulating the anti-oxidative system via activation of the PI3K/Akt/Nrf2 pathway and by regulating bile acid metabolism.

This study demonstrated that AG may mitigate ANIT-induced cholestatic liver damage by improving the bile flow rates, decreasing the concentrations of liver function markers and serum enzyme levels, enhancing liver histology, activating Nrf2 via the PI3K/Akt signaling pathway, and controlling bile acid transport.