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*

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

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 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

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

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

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

We conducted a randomized animal study to determine whether there is a cumulative effect on hemodynamics, pulmonary function, and gas exchange when low dose nitric oxide (NO) is added to partial liquid ventilation (PLV) in acute lung injury. ighteen newborn piglets were saline-lavaged repeatedly, and randomly divided into two groups: PLV with perfluorocarbon group (n=8) and lavage only (control) group (n=10). Perfluorodecalin (30 mL/kg) was instilled into the endotracheal tube for 30 min, followed by 5-10 mL/kg/hr. Fifteen minutes after the completion of perfluorodecalin dosing, NO (10 ppm) was added to the inspiratory gas in an "on/off" manner. Perfluorodecalin instillation produced a significant improvement in gas exchange, pulmonary mechanics, shunt, and pulmonary arterial pressure (PAP). The addition of NO produced a further significant improvement in PaO2 and PAP. The "on/off" response to NO was seen apparently in PAP, PaO2, dynamic compliance, and shunt. All the variables in control group were remained at near the after-lavage levels without significant improvements until the end of the experiment. We concluded that NO might have a cumulative effect on gas exchange when combined with PLV, and this might be attributable to deceased PAP and V/Q mismatching.
Administration, Inhalation ; Animals ; Animals, Newborn ; Fluorocarbons/metabolism ; Hemodynamic Processes ; *Liquid Ventilation ; Nitric Oxide/administration & dosage/*metabolism ; Plasma Substitutes/metabolism ; Pulmonary Gas Exchange/*physiology ; Random Allocation ; *Respiratory Distress Syndrome, Adult ; Respiratory Mechanics ; *Respiratory Physiology ; Support, Non-U.S. Gov't ; Swine

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

We sought to know whether there is a further improvement in gas exchange when partial liquid ventilation (PLV) is added to high-frequency oscillatory ventilation (HFOV) in a piglet model of saline lavage-induced acute lung injury. Seven 7-9 day-old newborn piglets of mixed strain were treated with repeated saline lavage to achieve a uniform degree of acute lung injury. Then, HFOV were applied to the subject. Four animals received two consecutive doses (15 mL/kg) of perfluorodecalin at 30-min interval (PFC+HFOV group). The other three animals remained on HFOV alone (HFOV-only group). Repetitive lung lavage led to a significant acute aggravation in both gas exchange and hemodynamic parameters. Subsequent application of HFOV produced a significant rapid recovery in both gas exchange and hemodynamic parameters to near baseline levels. During and after perfluorodecalin dosing, there were no significant changes in gas exchange or hemodynamic parameters over time in both groups, and no significant differences in gas exchange or hemodynamic parameters between groups. We concluded that the addition of 30 mL/kg of perfluorodecalin to HFOV showed no detrimental effect on hemodynamics, but did not produce a significant improvement in gas exchange over a three-hour period.
Animals ; Animals, Newborn ; Blood Pressure ; Fluorocarbons/*pharmacology ; Hydrogen-Ion Concentration ; Liquid Ventilation ; Lung/injuries/pathology ; Oscillometry ; Oxygen/metabolism ; Pulmonary Gas Exchange ; Respiratory Insufficiency ; Sodium Chloride/pharmacology ; Support, Non-U.S. Gov't ; Swine ; Time Factors