-Context -Cholestasis produces hepatocellular injury, leukocyte infiltration, ductular cells proliferation and fibrosis of liver parenchyma by extracellular matrix replacement. Objective -Analyze bile duct ligation effect upon glycosaminoglycans content and matrix metalloproteinase (MMPs) activities. Methods -Animals (6-8 weeks; n = 40) were euthanized 2, 7 or 14 days after bile duct ligation or Sham-surgery. Disease evolution was analyzed by body and liver weight, seric direct bilirubin, globulins, gamma glutamyl transpeptidase (GGT), alkaline phosphatase (Alk-P), alanine and aspartate aminotransferases (ALT and AST), tissue myeloperoxidase and MMP-9, pro MMP-2 and MMP-2 activities, histopathology and glycosaminoglycans content. Results -Cholestasis caused cellular damage with elevation of globulins, GGT, Alk-P, ALT, AST. There was neutrophil infiltration observed by the increasing of myeloperoxidase activity on 7(P = 0.0064) and 14 (P = 0.0002) groups which leads to the magnification of tissue injuries. Bile duct ligation increased pro-MMP-2 (P = 0.0667), MMP-2 (P = 0.0003) and MMP-9 (P<0.0001) activities on 14 days indicating matrix remodeling and establishment of inflammatory process. Bile duct ligation animals showed an increasing on dermatan sulfate and/or heparan sulfate content reflecting extracellular matrix production and growing mitosis due to parenchyma depletion. ConclusionCholestasis led to many changes on rats' liver parenchyma, as so as on its extracellular matrix, with major alterations on MMPs activities and glycosaminoglycans content. HEADINGS -Extrahepatic cholestasis. Glycosaminoglycans. Matrix metalloproteinases.

During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.

Iron deficiency is a public health problem that affects all age groups. Its main consequence is anemia, but it can also affect cognitive functions. Although the negative effects of iron deficiency on cognitive function have been extensively described, the underlying mechanism has not been fully investigated. Thus, to gain an unbiased insight into the effects of iron deficiency (ID) on discrete brain regions, we performed a proteomic analysis of the striatum and hippocampus of adult rats subjected to an iron restricted (IR) diets for 30 days. We found that an IR diet caused major alterations in proteins related to glycolysis and lipid catabolism in the striatum. In the hippocampus, a larger portion of proteins related to oxidative phosphorylation and neurodegenerative diseases were altered. These alterations in the striatum and hippocampus occurred without a reduction in local iron levels, although there was a drastic reduction in liver iron and ferritin. Moreover, the IR group showed higher fasting glycaemia than the control group. These results suggest that brain iron content is preserved during acute iron deficiency, but the alterations of other systemic metabolites such as glucose may trigger distinct metabolic adaptations in each brain region. Abnormal energy metabolism precedes and persists in many neurological disorders. Thus, altered energy metabolism can be one of the mechanisms by which iron deficiency affects cognitive functions.

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