The effect and mechanism of highland barley β-glucan in improving liver regeneration after partial hepatectomy

Studies have shown the beneficial effect of highland barley β-glucan (HBBG) on multiple acute and chronic liver diseases, however, whether it can improve liver regeneration following 2/3 partial hepatectomy (PH) is yet unknown. This study investigated the positive effect of β-glucan on liver regeneration in acute liver injury after PH. Before PH or CCl4 administration, mice were fed either a chow diet or that containing 5 or 10% HBBG for two weeks. The experimental mice were weighed on days 0, 1, and 2 after PH or CCl4 treatment, and the serum and liver tissue were collected. qRT-PCR, Western blotting, TUNEL staining, and immunostaining analysis were performed to measure the associated indices of proliferation and apoptosis of hepatocytes. We found that 5% HBBG promoted hepatocyte proliferation and liver regeneration and increased the liver/body weight ratio at 1 and 2 days after PH in mice. Mechanistically, HBBG activated the STAT3-CyclinD1 signaling pathway to increase hepatocyte proliferation, accelerating their transition from the G0 to S phase. Additionally, the HBBG intervention decreased hepatocyte apoptosis in the CCl4-induced liver injury model of mice. Concisely, HBBG can promote hepatocyte proliferation and liver regeneration via the STAT3-CyclinD1 signaling pathway in acute liver injury or PH

Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites

Excessive N-acetyl-p-benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The Glrx1 knockout mice (Glrx1−/−) and liver-specific overexpression of Glrx1 (AAV8-Glrx1) mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein S-glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. Glrx1−/− mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury