Liver injury in acute fatty liver of pregnancy: possible link to placental mitochondrial dysfunction and oxidative stress.

UNLABELLED: Acute fatty liver of pregnancy (AFLP) is a rare disorder which is fatal if not recognized and treated early. Delivery of the feto-placental unit results in dramatic improvement in maternal liver function, suggesting a role for the placenta. However, the mechanisms by which defects in the fetus or placenta lead to maternal liver damage are not well understood and form the focus of this study. Placenta and serum were obtained at delivery from patients with AFLP, and placental mitochondria and peroxisomes were isolated. Placental mitochondrial function, oxidative stress, and fatty acid composition as well as serum antioxidants, oxidative and nitrosative stress markers, and fatty acid analysis were carried out. Hepatocytes in culture were used to evaluate cell death, mitochondrial function, and lipid accumulation on exposure to fatty acids. Oxidative stress was evident in placental mitochondria and peroxisomes of patients with AFLP, accompanied by compromised mitochondrial function. Increased levels of arachidonic acid were also seen in AFLP placenta when compared to control. Patients with AFLP also had a significant increase in oxidative and nitrosative stress markers in serum, along with decreased antioxidant levels and elevated levels of arachidonic acid. These levels of arachidonic acid were capable of inducing oxidative stress in hepatocyte mitochondria accompanied by induction of apoptosis. Exposure to arachidonic acid also resulted in increased lipid deposition in hepatocytes. CONCLUSION: Oxidative stress in placental mitochondria and peroxisomes is accompanied by accumulation of toxic mediators such as arachidonic acid, which may play a causative role in maternal liver damage seen in AFLP.

Early activation of mucosal dendritic cells and macrophages in acute Campylobacter colitis and cholera: An in vivo study.

BACKGROUND AND AIM: Macrophages and dendritic cells are closely related mononuclear phagocytic cells. Little is known about their in vivo role in acute intestinal bacterial infections in humans. We undertook to evaluate these cells in rectal mucosal biopsies of patients with acute colitis. METHODS: All mucosal mononuclear phagocytic cells in rectal biopsies of patients with acute Campylobacter colitis (n = 5), shigellosis (n = 5), and cholera (n = 10) were evaluated ultrastructurally and compared with those in controls (n = 5). RESULTS: Mononuclear phagocytic cells in the superficial rectal mucosa showed a higher prevalence of ultrastructural features of activation in Campylobacter colitis and cholera than in controls. A lower prevalence of features of activation with increased monocytes was seen in shigellosis. Cells with the ultrastructural morphology of activated dendritic cells constituted 41% and 45% of all mononuclear phagocytic cells in two of five patients with Campylobacter colitis and 4-22% of cells in four of 10 patients with cholera. Their presence in patients with Campylobacter colitis was associated with significant surface epithelial damage and prominent acute inflammatory changes in the mucosa. CONCLUSIONS: This is the first ultrastructural study to show activated macrophages and dendritic cells in vivo in acute Campylobacter colitis and cholera. Dendritic cell activation occurred early in the clinical course of these infections. Surface epithelial damage may play a role in the activation of dendritic cells.

Retinoid metabolism during development of liver cirrhosis.

The changes in retinoid metabolism have been documented in liver cirrhosis. However, the dynamic alterations in levels of this vitamin between circulation and liver during development of the liver cirrhosis are not well understood. The aim of this study was to measure retinoids in the liver and circulation in parallel, during and after development of cirrhosis induced by carbon tetrachloride and thioacetamide. Retinoid levels were measured by HPLC. A decrease in retinaldehyde and total retinol, together with an increase in retinoic acid was evident in liver from both carbon tetrachloride or thioacetamide treated rats within a month after initiation of treatment. Activity of enzymes involved in retinoid metabolism such as retinaldehyde oxidase, retinaldehyde dehydrogenase, and retinaldehyde reductase were decreased in the liver. In parallel, levels of retinol and retinaldehyde in the serum were increased while retinoic acid was decreased. This study indicates that during development of cirrhosis, there is reciprocal transfer of retinoid metabolites between the circulation and the liver.