scholarly journals Complement Initiation Varies by Sex in Intestinal Ischemia Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Miaomiao Wu ◽  
Jennifer M. Rowe ◽  
Sherry D. Fleming
Keyword(s):  
Complement Activation ◽  
Intestinal Ischemia ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Dependent Manner ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia reperfusion (IR)-induced tissue injury represents an acute inflammatory response with significant morbidity and mortality. The mechanism of IR-induced injury is not fully elucidated, but recent studies suggest a critical role for complement activation and for differences between sexes. To test the hypothesis that complement initiation differs by sex in intestinal IR, we performed intestinal IR on male and female WT C57B6L/, C1q-/-, MBL-/-, or properdin (P)-/- mice. Intestinal injury, C3b and C5a production and ex vivo secretions were analyzed. Initial studies demonstrated a difference in complement mRNA and protein in male and female WT mice. In response to IR, male C1q-, MBL- and P-deficient mice sustained less injury than male WT mice. In contrast, only female MBL-/- mice sustained significantly less injury than female wildtype mice. Importantly, wildtype, C1q-/- and P-/- female mice sustained significant less injury than the corresponding male mice. In addition, both C1q and MBL expression and deposition increased in WT male mice, while only elevated MBL expression and deposition occurred in WT female mice. These data suggested that males use both C1q and MBL pathways, while females tend to depend on lectin pathway during intestinal IR. Females produced significantly less serum C5a in MBL-/- and P-/- mice. Our findings suggested that complement activation plays a critical role in intestinal IR in a sex-dependent manner.

scholarly journals Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Jiang ◽  
Zhen Zhou ◽  
Qing-tao Meng ◽  
Qian Sun ◽  
Wating Su ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Weight Ratio ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ginsenoside Rb1 ◽  
Intestinal Ischemia Reperfusion

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway.Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R.Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-)αbut decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-αand MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA.Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway.

scholarly journals Pathways of Complement Activation Following Intestinal Ischemia-Reperfusion in Macaque

2012 ◽  
Vol 31 (3) ◽  
pp. 228-233
Author(s):  
Lantao Xu ◽  
Yanyan Wu
Keyword(s):  
Complement Activation ◽  
Intestinal Ischemia ◽  
Alternative Pathway ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Polymorphonuclear Cells ◽  
Apoptosis Rate ◽  
Endogenous Protection ◽  
Total Complement ◽  
Intestinal Ischemia Reperfusion

Pathways of Complement Activation Following Intestinal Ischemia-Reperfusion in MacaqueComplement activation is a key component in the inflammation cascade. In the present study, intestinal ischemia-reperfusion (IIR) was introduced to macaques, and the pathways of complement activation in the multiple organ dysfunction syndrome (MODS) following IIR were investigated, which may provide evidence on the mechanisms underlying the endogenous protection in systemic inflammatory response. IIR was performed by clamping superior mesenteric artery and releasing clamp in 5 macaques. Immunization rate nephelometry and CH50 total complement detection were employed to measure the serum concentration of C3, C4, C-reactive protein (CRP) and total complements. Immunocytochemistry was carried out to detect the contents of IL-1 and NF-κB in polymorphonuclear cells (PMN). Flow cytometry was done to measure the apoptosis rate of PMN. At 24 h after IIR, the amount of total complement (106.6±18.07 U/mL) was reduced to 62.1±9.52 U/mL (p<0.05). In addition, the C3 was reduced by 30% (p<0.05) but C4 remained unchanged after IIR (0.1342±0.07 vs 0.1420±0.06, P>0.05). The apoptosis rate (15.4%±1.14%) of PMN was markedly reduced (3.5%±0.53%) following IIR (p<0.05) accompanied by increased contents of IL-1 and NF-κB. Moreover, CRP was also significantly elevated after IIR (4.33±1.13 mg/L vs 17.73±0.86 mg/L; p<0.01). Following IIR, complements are activated through the alternative pathway. Complement activation fragments can inhibit the apoptosis of PMN and elevate the expressions of acute phase inflammatory proteins including CRP and IL-1, which promotes the inflammation cascade and facilitates the occurrence of MODS.

scholarly journals Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ozkan Onal ◽  
Fahri Yetisir ◽  
A. Ebru Salman Sarer ◽  
N. Dilara Zeybek ◽  
C. Oztug Onal ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Intestinal Injury ◽  
Control Group ◽  
Injury Score ◽  
Tissue Samples ◽  
Intestinal Ischemia Reperfusion

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine.Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test.Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group.Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

scholarly journals Female and male mice have differential longterm cardiorenal outcomes following a matched degree of ischemia–reperfusion acute kidney injury

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle E. Soranno ◽  
Peter Baker ◽  
Lara Kirkbride-Romeo ◽  
Sara A. Wennersten ◽  
Kathy Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cardiovascular Outcomes ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice

AbstractAcute kidney injury (AKI) is common in patients, causes systemic sequelae, and predisposes patients to long-term cardiovascular disease. To date, studies of the effects of AKI on cardiovascular outcomes have only been performed in male mice. We recently demonstrated that male mice developed diastolic dysfunction, hypertension and reduced cardiac ATP levels versus sham 1 year after AKI. The effects of female sex on long-term cardiac outcomes after AKI are unknown. Therefore, we examined the 1-year cardiorenal outcomes following a single episode of bilateral renal ischemia–reperfusion injury in female C57BL/6 mice using a model with similar severity of AKI and performed concomitantly to recently published male cohorts. To match the severity of AKI between male and female mice, females received 34 min of ischemia time compared to 25 min in males. Serial renal function, echocardiograms and blood pressure assessments were performed throughout the 1-year study. Renal histology, and cardiac and plasma metabolomics and mitochondrial function in the heart and kidney were evaluated at 1 year. Measured glomerular filtration rates (GFR) were similar between male and female mice throughout the 1-year study period. One year after AKI, female mice had preserved diastolic function, normal blood pressure, and preserved levels of cardiac ATP. Compared to males, females demonstrated pathway enrichment in arginine metabolism and amino acid related energy production in both the heart and plasma, and glutathione in the plasma. Cardiac mitochondrial respiration in Complex I of the electron transport chain demonstrated improved mitochondrial function in females compared to males, regardless of AKI or sham. This is the first study to examine the long-term cardiac effects of AKI on female mice and indicate that there are important sex-related cardiorenal differences. The role of female sex in cardiovascular outcomes after AKI merits further investigation.

scholarly journals C3b-Independent Complement Activation in Ischemia/Reperfusion Mesenteric Tissue Injury in Autoimmune Prone (B6.MRL/lpr) Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-9
Author(s):  
J. Tofferi ◽  
S. Peng ◽  
C. M. Moratz
Keyword(s):  
Lupus Erythematosus ◽  
Complement Activation ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cobra Venom ◽  
Cobra Venom Factor ◽  
Inflammatory Tissue

Complement plays a critical role in the development of tissue injury in systemic lupus erythematosus. The B6.MRL/lpr mouse, an autoimmune prone mouse, exhibits accelerated and intensified tissue injury in the ischemia/reperfusion (IR) model. It has been demonstrated in nonautoimmune mice that inhibition of complement attenuates inflammatory tissue injury in IR models. The role of complement is not as clear in the B6.MRL/lpr strain. B6.MRL/lpr-C3 deficient animals are susceptible to injury, but long-term use of C3 inhibitors in B6.MRL/lpr-C3 competent animals restrained the development of nephritis. To clarify the role of complement in the B6.MRL/lpr strain, initial and midpathway inhibitors were evaluated. C1 inhibition attenuated tissue injury, thrombin deposition, and C5a generation in the B6.MRL/lpr strain. Downstream of C1 inhibition of C3 activation by administration of cobra venom factor suppressed IR injury in immune competent mice, but was not as effective in B6.MRL/lpr mice. C3 levels in both strains were decreased after cobra venom factor treatment; however, C5a generation, thrombin deposition, and tissue injury were observed in the B6.MRL/lpr strain. These studies suggest that in the B6.MRL/lpr autoimmune prone strain C1 activation leads to C3-dependent and C3-independent pathways of complement activation.

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