Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice.

Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance of glutamine in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis remains unclear. In the present study, the potential effects of glutamine on LPS/D-Gal-induced fulminant hepatitis were investigated. Pretreatment with glutamine decreased plasma activities of alanine and aspartate aminotransferases, and ameliorated hepatic morphological abnormalities in LPS/D-Gal-exposed mice. Glutamine pretreatment also inhibited LPS/D-Gal-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production. In addition, glutamine pretreatment decreased the level of cleaved cysteinyl aspartate-specific proteinase 3 (caspase-3), suppressed the activities of caspase-3, caspase-8, and caspase-9, and reduced the number of cells positive for TdT-mediated dUTP nick-end labeling in LPS/D-Gal-challenged mice. Interestingly, post-treatment with glutamine also provided protective benefits against LPS/D-Gal-induced acute liver injury, although these effects were less robust than those of glutamine pre-treatment. Thus, glutamine may have potential value as a pharmacological intervention in fulminant hepatitis.

Neuroprotective effects of curcumin against rats with focal cerebral ischemia-reperfusion injury.

The aim of the present study was to investigate the protective effects of curcumin and its effect on the methyl ethyl ketone/extracellular signal regulated kinase/cAMP­response element binding protein (MEK/ERK/CREB) pathway. The study was conducted in vivo and in vitro as follows: In vivo: Focal cerebral ischemia­reperfusion (IR) models of rats were made with the plug­line method. Adult male Sprague­Dawley rats were divided into four groups: Sham operation control group, IR and curcumin­treatment groups (100 mg/kg and IC, 300 mg/kg). The effects of curcumin on neurological deficit scores, brain water content and infarct volumes were identified. Transmission electron microscope was utilized to observe morphological changes of hippocampal neurons; hematoxylin and eosin staining was used to observe morphological changes of brain tissue; and the terminal deoxynucleotidyl transferase (TdT)­mediated dUTP nick end labeling method detected neurons apoptosis of hippocampal CA1. Finally, western blot analysis detected the expression of phosphorylated (p)­MEK, p­ERK, p­CREB, B­cell lymphoma­2 (Bcl­2) and Bcl­2 associated X protein (Bax). In vitro: An oxygen­glucose deprivation/reoxygenation method was used on primary cultured astrocytes to make cerebral ischemia­reperfusion models in vitro. Astrocytes were randomly divided into five groups: Normoxia, oxygen­glucose deprivation/reoxygenation (OGD/Reoxy), OGD/Reoxy + curcumin (5, 10, 20 µmol/l). The cell viability and toxicity were assessed by MTT and lactate dehydrogenase release assay, and levels of p­MEK, p­ERK and p­CREB proteins were analyzed by the western blotting method. Curcumin was demonstrated to improve nerve damage symptoms and infarct volume, reduce brain water content, relieve neuronal apoptosis and also increase the expression of p­MEK, p­ERK, p­CREB, Bcl­2 and reduce Bax levels in vivo and in vitro. In conclusion curcumin can mitigate focal cerebral ischemia­reperfusion injuries and this effect may be carried out through the MEK/ERK/CREB pathway.