Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity

<p>Abstract</p> <p>Background</p> <p>Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G₀), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose.</p> <p>Methods</p> <p>C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours.</p> <p>Results</p> <p>72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration.</p> <p>Conclusion</p> <p>RLS improves liver recovery from APAP hepatotoxicity.</p

Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-19F-NMR

The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using 19F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane