Protective Effect of Histidine Against the Hepatotoxic Effect of Tetrachloride Carbon by Reducing Nuclear Factor-kβ Pathway Signaling and Increasing the Reduced glutathione/ Oxidized glutathione Ratio in an Acute Liver Injury Rat Model
Kimia Hazrat Gholizadeh Namin, Sina MahdavifardAbstract
Background:
Oxidative stress resulting from toxic compounds, such as carbon tetrachloride (CCl 4 ), contributes to acute liver injury (ALI) and acute kidney malfunction by increasing nuclear factor-kβ (NF-kβ) pathway signaling following antioxidant resource depletion. Therefore, we investigated the effect of histidine (His) on hepatic NF-kβ signaling and markers of oxidative stress and inflammation in both serum and liver homogenates in an ALI rat model.
Methods:
Thirty-two rats were divided into four groups, each containing eight rats: untreated normal, ALI, and two similar groups receiving His (0.1% in drinking water for two weeks). ALI was induced in rats by intraperitoneal injection of CCl 4 (1 ml/kg) on the 15 th day. We evaluated the expression of hepatic NF-kβ and quantified markers of oxidative stress and inflammation in both serum and liver homogenates. Additionally, we measured biochemical liver function markers. Finally, we assessed histopathological changes in the liver following ALI simulation.
Results:
His protected the liver against fibrosis, necrosis, and reduced fatty changes. The treatment decreased hepatic NF-kβ expression, liver dysfunction parameters, and indicators of oxidative stress and inflammation. Furthermore, it increased systemic and hepatic antioxidant potential (
Conclusion:
Histidine ameliorated ALI, improved liver function, decreased NF-kβ signaling, and increased systemic and hepatic antioxidant potential by increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and antioxidant enzyme activities. The beneficial effects of His on the NF-kβ pathway and the increase in the GSH/GSSG ratio may be the key mechanisms of its actions.