OBJECTIVES: Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR. METHODS: A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH₂O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting. RESULTS: After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05). CONCLUSIONS PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.
Animals ; Caprylates ; Fatty Acids/pharmacology* ; Fluorocarbons ; Lipid Metabolism ; Lipid Metabolism Disorders/metabolism* ; Liver/metabolism* ; Male ; PPAR gamma ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism*

Alkanesulfonic Acids ; toxicity ; Animals ; Female ; Fluorocarbons ; toxicity ; Humans ; Male ; Mice ; Neovascularization, Physiologic ; drug effects ; Pedigree ; Placenta ; blood supply ; drug effects ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; genetics ; metabolism ; physiopathology ; RNA, Long Noncoding ; genetics ; metabolism

OBJECTIVETo investigate the effects of perfluorocarbon and ligustrazine in protecting the lungs against ischemia-reperfusion injury in rats.

METHDSForty SD rats with ischemia-reperfusion lung injury were randomized equally into control, ligustrazine, perfluorocarbon, and perfluorocarbon plus ligustrazine groups and received the corresponding treatment via the tail vein 5 min before reperfusion. The lung tissues were harvested and the levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α) were detected 3 h after reperfusion. The pathological changes and pathological scores of the lung tissues were analyzed.

RESULTSMDA and MPO levels were significantly lower and SOD activities significantly higher in the lung tissues in the 3 treatment groups than in the control group (P<0.05). The rats in the combined treatment group showed a significantly lower MPO level and a significantly higher SOD activity than those treated with ligustrazine or perfluorocarbon alone (P<0.05). No significant difference was found in TNF-α levels in the lung tissues among the 4 groups (P>0.05). The lung tissues in the control group showed obvious edema and exudation, and the tissues in ligustrazine and perfluorocarbon groups showed no edema but with a few red blood cells and exudation; no edema was found in the combined treatment group with only a small amount of exudation. The pathological scores differed significantly among the 4 groups.

CONCLUSIONPerfluorocarbon and ligustrazine, especially in combined use, can promote endogenous oxygen free radical scavenging, decrease peripheral blood proinflammatory cytokines, and inhibit neutrophils filtration in the lungs of rats with ischemia/reperfusion lung injury.

Animals ; Cytokines ; Fluorocarbons ; pharmacology ; Lung Injury ; drug therapy ; Malondialdehyde ; metabolism ; Peroxidase ; metabolism ; Protective Agents ; pharmacology ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDToll-like receptor-4 (TLR-4) is integrally involved in lipopolysaccharide (LPS) signaling and has a requisite role in the activation of nuclear factor-κB (NF-κB). The exact mechanisms that lend perfluorocarbon (PFC) liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls (AECs).

METHODSAECs (A549 cells, human lung adenocarcinoma cell line) were divided into four groups: control, PFC, LPS and LPS + PFC (coculture group) groups. Intercellular adhesion molecule-1 (ICAM-1) was detected by ELISA, tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting (proteins of I-κBa and NF-κB p65).

RESULTSICAM-1, TNF-α and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α and IL-8, the expression of TLR-4 mRNA and the activity of NF-κB.

CONCLUSIONSTaken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.

Blotting, Western ; Cell Line, Tumor ; Epithelial Cells ; drug effects ; immunology ; Fluorocarbons ; pharmacology ; Humans ; Inflammation ; chemically induced ; immunology ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Interleukin-8 ; genetics ; metabolism ; Lipopolysaccharides ; pharmacology ; NF-kappa B ; genetics ; metabolism ; Pulmonary Alveoli ; cytology ; Real-Time Polymerase Chain Reaction ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

The present study was to investigate in vitro the rat cardiomyocyte injury with targeting of home-made perfluorocarbon lipid particles with avidin-biotin interaction. Neonatal rat cardiomyocytes were cultured in vitro and divided into two groups: TNF-alpha activated group and non-activated group. Those in the TNF-alpha activated group were exposed to 200 ng/ml TNF-alpha solution for 6 hours and then cardiomyocytes in both groups were pretargeted with biotinylated ICAM-1 monoclonal antibodies, and were exposed to streptavidin, and then to homemade green fluorescently-labeled biotinylated perfluorocarbon lipid particles. Cardiomyocytes nucleus stained with Hoechst. The results were detected with fluorescence microscope. As a result, in TNF-alpha activated group, around blue fluorescent cardiomyocytes nucleus, a great amount of green fluorescent particles were found, while there were few green fluorescent particles in non-TNF activated group. It has been shown that ICAM-1 is expressed in the surface of cardiomyocytes when they are stimulated by TNF-alpha. Perfluorocarbon lipid particles associated with ICAM-1 monoclonal antibodies can be targeted to injured cardiomyocytes by avidin-biotin interaction.
Animals ; Animals, Newborn ; Antibodies, Monoclonal ; metabolism ; Cells, Cultured ; Contrast Media ; Female ; Fluorocarbons ; immunology ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipids ; chemistry ; Male ; Microspheres ; Myocytes, Cardiac ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; pharmacology ; Ultrasonography

BACKGROUNDPediatric patients are susceptible to lung injury. Acute lung injury (ALI) in children often results in a high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA).

METHODSTwelve Chinese immature piglets were induced to develop ALI by oleic acid. The animals were randomly assigned to two groups (n = 6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.

RESULTSCompared with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha both in plasma and tissue concentrations compared with MV group (P < 0.05).

CONCLUSIONSPartial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

Animals ; Fluorocarbons ; therapeutic use ; Hemodynamics ; drug effects ; Inflammation ; chemically induced ; therapy ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Liquid Ventilation ; methods ; Lung Injury ; immunology ; therapy ; Oleic Acid ; toxicity ; Random Allocation ; Respiration, Artificial ; Swine ; Tumor Necrosis Factor-alpha ; metabolism

The properties of polyethyleneimine-cholesterol cationic lipopolymer (PEI-Chol) as gene carries and its gene transfer efficiency in vitro with lipid microbubbles were presented in this paper. PEI-Chol lipopolymer was synthesized by linking cholesterol chloroformate to the amino groups of branched poly(ethyleneimine) (PEI) of 1 800. The structure and molecular weight of PEI-Chol were confirmed by IR, 1H NMR and MADI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry), respectively. The average molecular weight of PEI-Chol was approximately 2 000. The gene delivery system of bubble/PEI-Chol/DNA was constructed by mixed PEI-Chol/pDNA (N/P 10:1) complexes with lipid microbubbles (2-8 microm) which were prepared by DPPC, DSPE-PEG2000 and perfluoropropane with the reverse phase evaporation technique. pEGFP-Cl (enhanced green fluorescent protein) was used as report gene to investigate the DNA condensing ability of PEI-Chol lipopolymer by agarose gel electrophoresis. And their cytotoxicity and in vitro transfer efficiency of different complexes were compared with each other in A549 and MCF-7. The results indicated PEI-Chol lipopolymer can condense plasmid DNA when N/P ratio upto 4, PEI-Chol complexes and bubble/PEI-Chol/DNA complexes were nontoxic to A549 and MCF-7 when formulated at the N/P ratio of 10/1 as determined by MTT assay. This bubble/PEI-Chol/DNA delivery system provided good transfer efficiency with other desirable characteristics such as against-precipitation of plasma proteins. In conclusion, bubble/PEI-Chol/DNA complex is a novel non-viral gene delivery system.
1,2-Dipalmitoylphosphatidylcholine ; chemistry ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; Cell Survival ; Cholesterol ; chemistry ; Contrast Media ; DNA ; chemistry ; genetics ; Female ; Fluorocarbons ; chemistry ; Gene Transfer Techniques ; Genetic Vectors ; Green Fluorescent Proteins ; metabolism ; Humans ; Lipids ; chemistry ; Lung Neoplasms ; pathology ; Microbubbles ; Phosphatidylethanolamines ; chemistry ; Plasmids ; Polyethylene Glycols ; chemistry ; Polyethyleneimine ; chemistry ; Transfection ; methods

The shortage of healthy blood resource and the problem of virus infection have urged the study of blood substitute. The technologies of modified hemoglobin, perfluorocarbons and Hb-vesicles have been developing quickly, and some of which have already been formed into large-scale preparation and production. However, there is no completed evaluation system for the blood substitute at present, and it is still hard to estimate the function of blood substitute completely. This article takes the evaluation of the blood substitute as a key point, discusses the evaluation parameters of blood substitute, and presents the physical and chemical property, the availability and safety as well as the preservation condition of the blood substitute. The data concerned are based on the studies in China and abroad and referred to the latest progress all over the world.
Animals ; Blood Substitutes ; administration & dosage ; standards ; Chemical Phenomena ; Erythrocytes ; drug effects ; metabolism ; Fluorocarbons ; administration & dosage ; adverse effects ; Hemoglobins ; administration & dosage ; adverse effects ; Humans ; Quality Control

OBJECTIVETo study the effects of perfluorooctane sulfonate (PFOS) on contents of glutamate and activity of protein kinase C (PKC) and A (PKA) and ultrastructure injury in the brain of male mice and to explore the mechanism of neurotoxicity and patho-alteration resulted from PFOS.

METHODS44 male mice were randomly divided into four groups, who were respectively orally given 0, 5, 10, 20 mg/kg PFOS for 10 days. The Glu consents in the brain of the mice was measured with spectrophotometer and protein kinases activity were measured with non-radioactive assay of protein kinase and the changes of cerebral cortex ultrastructure were observed.

RESULTSContents of Glu in 10 and 20 mg/kg groups were (1.57 +/- 0.11) and (1.62 +/- 0.16) mmol/g prot respectively,which was significantly increased compared with the corresponding controlled group [(1.45 +/- 0.13) mmol/g prot] (F = 39.59, P < 0.05). PKC activity in 5, 10 and 20 mg/kg BW groups were (29.05 +/- 2.89), (33.65 +/- 3.82) and (34.20 +/- 3.16) pmol x min(-1) x (mg prot)-1 respectively, which was significantly increased compared with the corresponding control group [(24.53 +/- 2.88) pmol x min(-1) x (mg prot)-1] (F = 7.75, P < 0.05). Compared with the corresponding control group, PKA in 5, 10 and 20 mg/kg BW groups increased by (24.12 +/- 3.86)%, (34.02 +/- 3.04)% and (33.42 +/- 3.71)% with a statistical significance (F = 26.27, P < 0.01). The exposed mice had cerebral cortex ultrastructure injury of cell nucleus envelope hollow.

CONCLUSIONExposure to PFOS increases Glu contents and activity of PKC and PKA in mouse brain and induce the cerebral cortex ultrastructural injury, a possible mechanism of the neurotoxicity caused by PFOS.

Alkanesulfonic Acids ; toxicity ; Animals ; Brain ; drug effects ; metabolism ; Brain Chemistry ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Fluorocarbons ; toxicity ; Glutamic Acid ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Protein Kinase C ; metabolism

Red blood cell substitutes are a group of oxygen carriers designed to temporarily replace transfused blood. Current developing products include perfluorocarbon-based and hemoglobin-based oxygen carrier. Each product is unique in its limitations and advantages. A number of products are in advanced clinical trials and nearing market. When they are available for use it is likely that development will accelerate and even better products will substantially alleviate the world-wide shortage of blood for transfusion.
Blood Substitutes ; chemistry ; pharmacology ; therapeutic use ; Fluorocarbons ; chemistry ; pharmacology ; therapeutic use ; Hemoglobins ; chemistry ; pharmacology ; therapeutic use ; Humans ; Oxygen ; metabolism ; Recombinant Proteins ; chemistry ; pharmacology ; therapeutic use