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To investigate the protective mechanisms of an 85 % pure extract of (−) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD). Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses. Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats. Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.

Multiple lines of evidence suggest a role for endogenous lipopolysaccharides in toxin-induced liver injury. Toll-like receptor 4 has recently been implicated as a cell surface receptor important for lipopolysaccharide responsiveness. In these experiments, we sought to determine the role of toll-like receptor 4 in acute liver injury by carbon tetrachloride by utilizing the naturally occurring toll-like receptor 4 mutant and wild-type mice strains. Mice were injected with either carbon tetrachloride or the carrier. Serum transaminase levels peaked at 24 hr after carbon tetrachloride administration for both wild-type and mutant mice, with no significant histological difference in initial liver injury between the two groups. However, an overall decrease in hepatocyte proliferation was found in the mutant mice. Examination of the liver tissue revealed significant decreases in intrahepatic expressions of proinflammatory mediators. In conclusion, our results suggest that toll-like receptor 4 is important in the hepatic regenerative response to CCl4 liver injury via its role in modulating the inflammatory response to hepatic injury.

We investigated the association between vitamin E, lipid peroxidation and eicosanoid production in experimental alcoholic liver injury. We used the intragastric feeding rat model in which animals were fed corn oil and ethanol (CO+E) and corn oil and dextrose (CO+D) for 2 and 4 week periods. At sacrifice, we measured plasma levels of alpha-tocopherol, 8-isoprostane, thromboxane B2 (TXB2) and 6-ketoprostaglandin F1 alpha (6-KetoPGF1 alpha). Animals fed CO+E had significantly lower concentrations of alpha-tocopherol and higher concentrations of 8 isoprostane at both 2 and 4 weeks. a significant inverse correlation was seen between alpha-tocopherol concentrations and the TXB2: PGF1 alpha ratio (r = 0.72, p0.01). A positive correlation was seen between the TXB2: PGF1 alpha ratio and 8 isoprostane levels (r = 0.84, p0.001). These results suggest that vitamin E depletion and enhanced lipid peroxidation may affect eicosanoid metabolism in experimental alcoholic liver disease in such a way so as to increase the thromboxane to prostacyclin ration.

We evaluated whether arterial blood samples for pH and blood gas analysis need to be transported on ice. We found that although the changes in pH, pCO2 and pO2 were greater in samples kept at room temperature versus those kept on ice, the difference was probably not of clinical significance until the period of time after arterial puncture exceeded 20 minutes. We recommend that arterial blood samples do not need to be kept on ice if the analysis for pH and gases is performed within 20 minutes of blood being drawn.

The usefulness of pretreatment biochemical parameters in the prediction of nephrotoxicity associated with cisplatin treatment was studied. Twenty-two patients, who received 29 cycles of cisplatin, were evaluated. Cisplatin was given every 3-4 weeks with saline and mannitol. Azotemia occurred in almost all patients and was transient, peaking 1-2 weeks after therapy. The change in serum creatinine from baseline to peak correlated inversely with pretreatment serum albumin (r = -0.73; P less than 0.01) and with pretreatment uric acid (r = 0.76; P less than 0.01). Ten patients with uric acid levels of less than 6 mg/dl were receiving allopurinol. The competition between organic anions and cisplatin for excretion may, in part, explain the protective effects of hypouricemia. Hypoalbuminemia affects peritubular oncotic pressure and may in turn affect platinum excretion. Hypoalbuminemia also reduces the half-life of cisplatin, exposing the kidney to more of the unbound filterable drug.