In the current investigation, Annona muricata Linn. lyophilized fruit pulp powder was evaluated for its hepatoprotective activity induced by paracetamol or acetaminophen (APAP). Male Sprague Dawley rats were orally pre-treated 15 days with A. at low (1 g/kg b.wt) and high doses (2 b.wt). Silymarin (100 mg/kg) administered as standard drug. Hepatotoxicity using APAP, in a single oral administrat...

Increasing model reuse and facilitating repurposing is expected to expand simulation use for better understanding biological phenomena. We demonstrate doing so in the context of liver diseases caused by toxic exposure to xenobiotics. A clinical goal is improved mechanistic explanations of how damage is generated, which can lead to new strategies to block and/or reverse injury. A goal for this w...

resistance of the weanling rat to acetaminophen (ap ap)-induced hepatotoxicity is manifested with regard to a surge in apap-glutathione (osh) conjugate formation in the liver [allameh et al. mech aging dev 95(1997)71]. the present study was conducted to assess the role of this detoxification pathway in apapinduced lipid per6xidationin the liver. lipid peroxidation measured as thiobarbituric aci...

Acetaminophen (APAP) hepatotoxicity is the most common cause of drug-induced liver injury and N-acetylcysteine (NAC) is the primary antidote of APAP poisoning. Wuzhi tablet (WZ), the active constituents well identified and quantified, is a preparation of an ethanol extract of Schisandra sphenanthera and exerts a protective effect toward APAP-induced hepatotoxicity in mice. However, the clinical...

The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocyt...

glutathione s-transferase (gst) is a superfamily enzyme which plays a major role indetoxification of xenobiotic compounds by catalyzing the conjugation of xenobiotic to cellular glutathione(gsh). gst-p is an important class of gsts which is expressed during the early stage of life and duringdevelopmental stages. its activity is relatively high during embryogenesis and immediately after birth an...

Acetaminophen (APAP) hepatotoxicity is mediated by N-acetyl- p -benzoquinone imine (NAPQI), a highly toxic metabolite generated cytochrome P450 2E1 (CYP2E1). Thus, pathological conditions increasing CYP2E1 activity can favour APAP-induced liver injury, which characterized massive hepatocellular necrosis and secondary sterile inflammation. In recent work, Wang et al. showed that was exacerbated ...

Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC) and transplanted into livers of immunodeficient Pfp/Rag2⁻/⁻ mice treated with a suble...

The relationship between acetaminophen (APAP) reactive metabolite formation, nitrotyrosine (NT) production, and cytokine elevation in APAP toxicity was investigated. Mice were dosed with 300 mg/kg of APAP and sacrificed at 1, 2, 4, 8, and 12 h. Serum aspartate aminotransferase (AST) was elevated by 4 h. The relative amount of NT correlated with toxicity and was localized in the necrotic cells. ...

Schisandra sphenanthera is widely used as a tonic and restorative in many countries to enhance the function of liver and other organs. Wuzhi tablet (WZ) is a preparation of an ethanol extract of Schisandra sphenanthera. Our previous study demonstrated that WZ exerted a protective effect toward acetaminophen (APAP)-induced hepatotoxicity. However, the molecular mechanisms of this protection rema...