RESUMO
This study investigated the effects of a fish oil-based lipid emulsion (FO) on local skeletal muscle and remote renal damage at 72â¯h post-reperfusion in a murine model of hind limb ischemia-reperfusion (IR) injury. Mice were assigned to 1 sham group and 3 IR groups. The IR groups were treated daily with either saline or FO from 3â¯days prior to limb ischemia till 3â¯days after reperfusion. Limb IR was induced by applying a 4.5-oz orthodontic rubber band above the left greater trochanter for 120â¯min followed by band-released reperfusion for 72â¯h. Mice were then sacrificed to harvest blood, muscle, and kidney for analysis. The results showed that IR injury led to upregulation of pro-inflammatory monocytes in blood, infiltration of leukocytes into injured muscle, and over-expression of pro-inflammatory genes in muscle and kidney tissues. Supplementing FO either before or after IR injury alleviated IR-induced inflammatory gene expressions in muscle and kidney tissues. Furthermore, FO given after IR injury reduced circulating pro-inflammatory monocytes, limited muscle leukocytic infiltration, and improved renal histology. These results suggest that FO may protect the muscles from IR injury. FO given after IR injury can better downregulate the inflammation seen in IR-induced remote kidney injury.
Assuntos
Óleos de Peixe/farmacologia , Membro Posterior/irrigação sanguínea , Nefropatias/metabolismo , Rim/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Emulsões , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia , Rim/patologia , Nefropatias/patologia , Masculino , Camundongos , Distribuição Aleatória , Traumatismo por Reperfusão/patologiaRESUMO
This study investigated the effects of a fish oil- (FO-) based lipid emulsion on muscle leukocyte chemotaxis and inflammatory responses in a murine model of limb ischemia-reperfusion (IR) injury. Mice were assigned randomly to 1 sham (sham) group, 2 ischemic groups, and 2 IR groups. The sham group did not undergo the ischemic procedure. The mice assigned to the ischemic or IR groups were pretreated intraperitoneally with either saline or FO-based lipid emulsion for 3 consecutive days. The IR procedure was induced by applying a 4.5 oz orthodontic rubber band to the left thigh above the greater trochanter for 120 min and then cutting the band to allow reperfusion. The ischemic groups were sacrificed immediately while the IR groups were sacrificed 24 h after reperfusion. Blood, IR-injured gastrocnemius, and lung tissues were collected for analysis. The results showed that FO pretreatment suppressed the local and systemic expression of several IR-induced proinflammatory mediators. Also, the FO-pretreated group had lower blood Ly6ChiCCR2hi monocyte percentage and muscle M1/M2 ratio than the saline group at 24 h after reperfusion. These findings suggest that FO pretreatment may have a protective role in limb IR injury by modulating the expression of proinflammatory mediators and regulating the polarization of macrophage.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Emulsões/uso terapêutico , Óleos de Peixe/uso terapêutico , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Modelos Animais de Doenças , Precondicionamento Isquêmico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismoRESUMO
Tumor lysis syndrome (TLS) occurring after surgical resection of right atrium (RA) and inferior vena cava (IVC) tumor thrombus is a very rare but insidious condition. We report a case of hepatocellular carcinoma who developed TLS after uneventful excision of RA+IVC tumor thrombus under median sternotomy and cardiopulmonary bypass (CPB). Although the procedure was not expected to arouse massive tumor cell necrosis, post-operative course was complicated by metabolic acidosis, hypocalcemia, and progressive hyperkalemia indicative of TLS. Unfortunately, laboratory diagnosis of TLS was delayed under conditions of continuous renal replacement therapy (CRRT) for peri-operative acute renal failure. Despite all efforts, the patient died 36 hours after surgery due to lethal arrhythmia and disseminated infarction of the kidneys, spleen, and liver.
RESUMO
Obesity is a global health problem with an up-regulated inflammatory reaction. Obesity-induced endothelial progenitor cells (EPCs) dysfunction is associated with vascular complications that may contribute to critical limb ischemia. Arginine (Arg) is an amino acid with immune-modulatory property and has been found to promote EPCs mobilization in disease conditions. Thus in the present investigation, we hypothesized that arginine given to a murine model of diet-induced obesity would increase circulating EPCs and mitigate the inflammatory reactions in response to limb ischemia. Mice were divided into normal group (NC), high-fat group (HC), and high-fat Arg group (HA). Mice in the HC group were fed with a diet containing 60% energy as fat for 8 weeks, while HA group were initially fed with the same high-fat diet for 4 weeks and later shifted to a high-fat diet enriched with 2% Arg for the remaining 4 weeks. Then mice in the HC and HA groups underwent ischemic operations and were euthanized at either day 1 or day 7 after limb ischemia. The results showed that, compared to the ischemic HC group, the ischemic HA group had higher circulating EPCs at day 1 post-ischemia and higher muscle stromal cell-derived factor-1 and interleukin (IL)-10 mRNA expressions at day 7 after ischemia. In contrast, plasma leptin concentration and expressions of IL-1ß and tumor necrosis factor-α mRNAs by adipocytes were down-regulated. These findings suggest that obese mice treated with Arg-containing high-fat diet enhanced circulating EPCs percentage and attenuated inflammatory reaction in response to limb ischemia.
Assuntos
Arginina/uso terapêutico , Dieta Hiperlipídica , Células Progenitoras Endoteliais/efeitos dos fármacos , Membro Posterior/irrigação sanguínea , Inflamação/prevenção & controle , Isquemia/complicações , Obesidade/complicações , Adipócitos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Arginina/farmacologia , Movimento Celular , Quimiocina CXCL12/metabolismo , Células Progenitoras Endoteliais/fisiologia , Endotélio Vascular/patologia , Membro Posterior/patologia , Inflamação/etiologia , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Isquemia/metabolismo , Leptina/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Músculos/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologiaRESUMO
OBJECTIVE: This study investigated whether the administration of L-Arginine, the precursor of nitric oxide, increases the percentages of blood endothelial progenitor cells and protects against ischemia/reperfusion induced inflammatory response in a mouse model of hind-limb IR injury. METHOD: C57BL/6 mice were randomized to one normal-control and four ischemia/reperfusion groups. The normal-control group did not undergo an ischemia/reperfusion procedure but mice in the ischemia/reperfusion groups were subjected to 150 min of unilateral hind-limb ischemia. The ischemia/reperfusion groups were subjected to either intravenous saline or L-Arginine (300 mg/kg body weight) administration before reperfusion and then sacrificed at either 24 h or 48 h after reperfusion. Blood and muscle tissues were collected for analysis. RESULTS: Ischemia/reperfusion injury led to a significant decrease in the percentage of blood endothelial progenitor cells and plasma nitric oxide concentration but plasma interleukin-6 levels and gene expression of inflammatory cytokines in injured muscle tissue were elevated. In contrast to the saline groups, those with L-Arginine administration were able to maintain a normal level of blood endothelial progenitor cells. In addition, after reperfusion, concentrations of nitric oxide, matrix metallopeptidase-9, and vascular endothelial growth factor in plasma were upregulated but keratinocyte-derived chemokine and monocyte chemoattractant protein-1 messenger RNA expressions in muscle were attenuated 48 h after reperfusion. Histologic findings also demonstrated a significant reduction of ischemia/reperfusion-induced muscle injury when L-Arginine was administered. CONCLUSION: A single dose of L-Arginine administration before reperfusion increases the percentage of endothelial progenitor cells and reduces the inflammatory reaction locally and systemically after ischemia/reperfusion injury.
Assuntos
Arginina/administração & dosagem , Células Progenitoras Endoteliais/efeitos dos fármacos , Membro Posterior/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismoRESUMO
This study investigated the influence of intravenous arginine (Arg) administration on alteration of circulating proangiogenic cells and remote lung injury in a model of polymicrobial sepsis. Mice were assigned to one normal control group (NC) and two sepsis groups that were induced by cecal ligation and puncture (CLP). One of the sepsis groups was injected with saline (SS), whereas the other (SA) was administered with a single bolus of 300 mg Arg/kg body weight via the tail vein 1 h after CLP. Septic mice were sacrificed at either 24 or 48 h after CLP, with their blood and lung tissues collected for analysis. Results showed that septic groups had higher proangiogenic cells releasing factors and proangiogenic cells percentage in blood. Also, concentration of inflammatory cytokines and expression of angiopoietin (Angpt)/Tie-2 genes in lung tissues were upregulated. Arg administration promoted mobilization of circulating proangiogenic cells while it downregulated the production of inflammatory cytokines and expression of Angpt/Tie-2 genes in the lung. The results of this investigation suggested that intravenous administration of Arg shortly after the onset of sepsis enhanced the mobilization of circulating proangiogenic cells, maintained the homeostasis of the Angpt/Tie-2 axis, and attenuated remote organ injury in polymicrobial sepsis.
Assuntos
Arginina/uso terapêutico , Infecções Bacterianas/microbiologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Lesão Pulmonar/prevenção & controle , Neovascularização Fisiológica/efeitos dos fármacos , Sepse/tratamento farmacológico , Angiopoietinas/metabolismo , Animais , Arginina/administração & dosagem , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Células Progenitoras Endoteliais/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intravenosas , Lesão Pulmonar/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor TIE-2/genética , Receptor TIE-2/metabolismoRESUMO
This study investigated the effects of glutamine (GLN) administration on circulating endothelial progenitor cells (EPCs) and lung angiopoietin (Ang) gene expressions in polymicrobial sepsis. Mice were randomly assigned to a normal control group (NC), septic saline group (SS), and septic GLN group (SG). All mice were fed with a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The mice in SS group were injected with saline, whereas SG group administered 0.75âg GLN/kg body weight once via tail vein 1âh after CLP. Mice were killed 24 and 48âh after CLP. Their blood and lungs were collected for further analysis. The results showed that, compared with normal mice, sepsis resulted in higher C-X-C motif chemokine-12, vascular endothelial growth factor, nitric oxide levels, and a higher circulating EPC percentage. In addition, inflammatory cytokine concentrations and Ang-2 gene expression were upregulated in lung tissues. GLN administration enhanced the mobilization of EPC, and downregulated inflammatory cytokine production and the Ang-2 gene expressions in lungs. Histopathological findings showed that the extent of inflammatory lesions of the lung alveolar was less severe in the SG group than the SS group after CLP. Our results suggest that a single dose of intravenous GLN administration after initiation of sepsis promotes the mobilization of circulating EPC, and modulates the balance of Ang-Tie2 axis that may improve the vascular function, ameliorate inflammation, and protect lung injury against polymicrobial sepsis.
Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Glutamina/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Sepse/tratamento farmacológico , Animais , Citocinas/metabolismo , Células Progenitoras Endoteliais/metabolismo , Ligadura , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ribonuclease Pancreático/genética , Ribonuclease Pancreático/metabolismoRESUMO
Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 0.05). Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05). Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05), at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Óleos de Peixe/farmacologia , Inflamação/prevenção & controle , Rim/efeitos dos fármacos , Sepse/tratamento farmacológico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Biomarcadores/sangue , Ceco/microbiologia , Ceco/cirurgia , Citocinas/sangue , Citocinas/genética , Modelos Animais de Doenças , Emulsões Gordurosas Intravenosas , Óleos de Peixe/administração & dosagem , Regulação da Expressão Gênica , Inflamação/sangue , Inflamação/etiologia , Mediadores da Inflamação/sangue , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Ligadura , Masculino , Camundongos Endogâmicos ICR , Punções , Sepse/sangue , Sepse/microbiologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , TriglicerídeosRESUMO
BACKGROUND: This study investigated the effects of intravenous glutamine (GLN) administration on the expression of adhesion molecules and inflammatory mediators in a mice model of hind limb ischemia/reperfusion (IR) injury. METHODS: There were 3 IR groups and 1 normal control (NC) group. The NC group did not undergo the IR procedure. Mice in the IR groups underwent 90 minutes of limb ischemia followed by a variable period of reperfusion. Ischemia was performed by applying a 4.5-oz orthodontic rubber band to the left thigh. Mice in one IR group were sacrificed immediately after reperfusion. The other 2 IR groups were injected once with either 0.75 g GLN/kg body weight (G group) or an equal volume of saline (S group) via tail vein before reperfusion. Mice in the S and G groups were subdivided and sacrificed at 4 or 24 hours after reperfusion. RESULTS: IR enhanced the inflammatory cytokine gene expressions in muscle. Also, plasma interleukin (IL)-6 levels, blood neutrophil percentage, and the adhesion molecule and chemokine receptors expressed by leukocytes were upregulated after reperfusion. The IR-induced muscle inflammatory mediator gene expressions, blood macrophage percentage, and plasma IL-6 concentration had declined at an early or a late phase of reperfusion when GLN was administered. Histologic findings also found that remote lung injury was attenuated during IR insult. CONCLUSIONS: A single dose of GLN administration immediately after sublethal lower limb ischemia reduces the inflammatory reaction locally and systemically; this may offer local and distant organ protection in hind limb IR injury.
Assuntos
Glutamina/farmacologia , Membro Posterior/efeitos dos fármacos , Inflamação/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/sangue , Citocinas/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Membro Posterior/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Neutrófilos/metabolismoRESUMO
This study investigated the effect of glutamine (GLN) on expressions of small intestinal intraepithelial lymphocyte (IEL) γδT-cell proinflammatory cytokines and apoptotic regulatory factor genes in a mouse model of hindlimb ischemia/reperfusion (IR) injury. Mice were assigned to a normal control group and three IR groups. Mice in the normal control group received no ischemia treatment, whereas IR groups had hindlimb ischemia for 90 min with subsequent 0 (IR0) or 24 h (IR24) of reperfusion. The IR0 group was sacrificed immediately after reperfusion. The IR24S group was injected with saline, and the IR24G group was given 0.75 g GLN/kg of body weight once via a tail vein before reperfusion. The IR24 groups were sacrificed 24 h after reperfusion. Small intestinal IEL γδT cells of the animals were isolated for further analysis. Results showed that IR injury resulted in lower small intestinal IEL γδT-cell percentages and higher proinflammatory cytokine messenger RNA expressions of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α by IEL γδT cells. Compared with the IR24S group, the IR24G group had a higher IEL γδT-cell percentage. Multiples of change of messenger RNA of proliferation gene expressions of the antiapoptotic Bcl-xl (B-cell lymphoma-extra large) and IL-7 receptor in the IR24G group were higher, whereas expressions of the keratinocyte growth factor and bacterial lectin regenerating islet-derived (Reg)IIIγ were lower in IEL γδT cells. Histological findings also showed that damage to the intestinal mucosa was less severe in the IR group with GLN. These results indicated that a single dose of GLN administered before reperfusion maintained small intestinal IEL γδT cell populations and reduced expressions of intestinal inflammatory cytokines, which may have consequently ameliorated the severity of IR-induced small intestinal epithelial injury.