A diet containing glycine improves survival in endotoxin shock in the rat

1996 ◽  
Vol 271 (1) ◽  
pp. G97-G103 ◽  
Author(s):  
K. Ikejima ◽  
Y. Iimuro ◽  
D. T. Forman ◽  
R. G. Thurman
Keyword(s):  
Intravenous Injection ◽  
Kupffer Cells ◽  
Ischemia Reperfusion ◽  
Control Diet ◽  
Hepatic Necrosis ◽  
Endotoxin Shock ◽  
Sprague Dawley ◽  
Hepatic Ischemia ◽  
Necrosis Factor Alpha

In this study, we investigated the effects of a glycine-containing diet (5%) on mortality and liver injury due to intravenous injection of endotoxin [Escherichia coli lipopolysaccharide (LPS)] in Sprague-Dawley rats in vivo. Fifty percent of the rats fed control diet died within 24 h after an intravenous injection of LPS (10 mg/kg), whereas feeding the rats glycine totally prevented mortality and markedly reduced an LPS-induced elevation of serum transaminase levels, hepatic necrosis, and lung injury. The elevation in serum tumor necrosis factor-alpha (TNF-alpha) due to LPS was also blunted and delayed significantly by glycine feeding. In a two-hit model (hepatic ischemia-reperfusion and injection of sublethal LPS), all rats fed control diet died, whereas 83% of glycine-fed animals survived with a significant reduction in transaminases and improved liver and lung histology. LPS elevated intracellular Ca2+ concentration ([Ca2+]i) in cultured Kupffer cells, an effect blocked almost completely by glycine. Glycine most likely reduces injury and mortality by preventing the LPS-induced elevation of [Ca2+]i in Kupffer cells, thereby minimizing toxic eicosanoid and cytokine production.

Bidirectional effects of hepatic ischemia/reperfusion on E. coli-induced TNF-alpha gene expression

1996 ◽  
Vol 270 (1) ◽  
pp. R289-R297 ◽  
Author(s):  
N. A. Epperly ◽  
A. J. Lechner ◽  
C. A. Johanns ◽  
R. O. Webster ◽  
G. M. Matuschak
Keyword(s):  
Gene Expression ◽  
Ischemia Reperfusion ◽  
Low Flow ◽  
Tnf Alpha ◽  
Heat Inactivation ◽  
Sprague Dawley ◽  
Hepatic Ischemia ◽  
Necrosis Factor Alpha ◽  
E Coli ◽  
Alpha Gene

We tested the hypothesis that gram-negative bacteremia (GNB) and brief (30 min) reductions in the hepatic O2 supply by low-flow ischemia differentially modulate tumor necrosis factor-alpha (TNF-alpha) gene expression owing to sequence-specific activation of cyclooxygenase vs. complement (C) pathways. Buffer-perfused Sprague-Dawley rat livers (n = 82) were studied over 180 min after intraportal 10(9) live E. coli serotype 055:B5 (EC) or 0.9% NaCl (NS) at t = 0. Compared with EC and NS controls receiving constant-flow perfusion, sequential GNB and ischemia/reperfusion (I/R) were studied in EC + 30 I/R and NS + 30 I/R livers, in which 30 min of ischemia (I) beginning 0.5 h after EC or NS was followed by 120 min of reperfusion (R). This sequence was reversed in 30 I/R + EC and 30 I/R + NS groups. Bacterial clearance, bioactive and antigenic TNF-alpha, prostaglandin E2 (PGE2), and hepatic O2 uptake and performance were serially assessed. Venous TNF-alpha increased in EC controls to peak at 155 +/- 29 U/ml after 180 min (P < 0.001 vs. NS controls) as did hepatic TNF-alpha mRNA. Both TNF-alpha transcripts and protein levels were markedly attenuated in EC + 30 I/R (P < 0.001 vs. EC) despite equivalent EC clearance by Kupffer cells. Indomethacin (10(-5) M) decreased I/R-induced PGE2 secretion and restored TNF-alpha to control levels. In contrast, TNF-alpha levels in 30 I/R + EC perfusates exceeded those of EC + 30 I/R livers (P < 0.05) and were indistinguishable from EC controls. Allopurinol pretreatment but not heat inactivation of C or infusion of soluble human complement receptor type 1 inhibited TNF-alpha production in 30 I/R + EC organs. These results identify a novel sequence-dependent interaction whereby hepatic O2 deprivation after GNB downregulates TNF-alpha via generation of cyclooxygenase metabolites, whereas ischemia preceding GNB increases cytokine expression via reactive O2 species but not C activation.

scholarly journals N6-methyladenosine demethylase FTO impairs hepatic ischemia–reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ying Dong Du ◽  
Wen Yuan Guo ◽  
Cong Hui Han ◽  
Ying Wang ◽  
Xiao Song Chen ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fragmentation ◽  
Hepatic Ischemia ◽  
Adeno Associated Virus ◽  
Downstream Target ◽  
Hepatic Ischemia Reperfusion

AbstractDespite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.

Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

1998 ◽  
Vol 275 (5) ◽  
pp. R1468-R1477 ◽  
Author(s):  
Scott K. Powers ◽  
Haydar A. Demirel ◽  
Heather K. Vincent ◽  
Jeff S. Coombes ◽  
Hisashi Naito ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Control Group ◽  
Sprague Dawley ◽  
Endurance Exercise Training ◽  
Nonprotein Thiols

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.

Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo

2001 ◽  
Vol 281 (2) ◽  
pp. H679-H688 ◽  
Author(s):  
P. R. Ramires ◽  
L. L. Ji
Keyword(s):  
Oxidative Damage ◽  
Antioxidant Defense ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Group Versus ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Lactate Dehydrogenase Release

The present study examined the effects of oral reduced glutathione (GSH) supplementation in conjunction with endurance training on contractile function, antioxidant defense, and oxidative damage in response to ischemia-reperfusion (I/R) in rat hearts. Female Sprague-Dawley rats (age 4 mo, n = 72) were randomly assigned to a treadmill-trained (T; 25 m/min, 15% grade, for 75 min/day, 5 days/wk, for 10 wk) or untrained (U) group. Each group was further divided into rats receiving 5 g GSH/kg diet during the final 17 days of training (GSH-S) and control (C) groups. One-half of each group of rats was subjected to I/R by surgical occlusion of the main coronary artery for 45 min, followed by 30-min reperfusion or sham operation. Left ventriclar (LV) peak systolic pressure (LVSP) and contractility (+dP/d t), measured with a catheter inserted into the LV via the carotid artery, decreased with I/R in all groups ( P< 0.05). However, LVSP with I/R in the T/GSH-S group was 9.5%, 17%, and 18% higher ( P < 0.05) than that in the U/GSH-S, T/C, and U/C groups, respectively. +dP/d t with I/R was 19%, 27%, and 29% ( P < 0.05) greater in the T/GSH-S group versus the T/C, U/GSH-S, and U/C groups, respectively. I/R decreased heart GSH content by 12–17% ( P < 0.05) and increased oxidized glutathione (GSSG) by 20–27% ( P < 0.05). T/GSH-S hearts showed 15% higher GSH ( P < 0.05) and a 32% higher GSH-to-GSSG ratio ( P < 0.05) than the U/C group at the end of I/R. Myocardial superoxide dismutase, GSH peroxidase, glutathione reductase, and γ-glutamyl transpeptidase activities were increased with treadmill training in both GSH-S and C rats. I/R induced myocardial lipid peroxidation and lactate dehydrogenase release were attenuated with T/GSH-S treatment. The present data indicate that training in conjunction with dietary GSH supplementation can increase myocardial GSH content and antioxidant defense capacity, thereby protecting the intact heart against oxidative damage and functional retardation caused by I/R.

Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

2001 ◽  
Vol 91 (5) ◽  
pp. 2205-2212 ◽  
Author(s):  
Haydar A. Demirel ◽  
Scott K. Powers ◽  
Murat A. Zergeroglu ◽  
R. Andrew Shanely ◽  
Karyn Hamilton ◽  
...  
Keyword(s):  
Heat Stress ◽  
Maximum Rate ◽  
Treadmill Exercise ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Antioxidant Defenses ◽  
Whole Body ◽  
Sprague Dawley ◽  
Short Term

These experiments examined the independent effects of short-term exercise and heat stress on myocardial responses during in vivo ischemia-reperfusion (I/R). Female Sprague-Dawley rats (4 mo old) were randomly assigned to one of four experimental groups: 1) control, 2) 3 consecutive days of treadmill exercise [60 min/day at 60–70% maximal O2 uptake (V˙o 2 max)], 3) 5 consecutive days of treadmill exercise (60 min/day at 60–70%V˙o 2 max), and 4) whole body heat stress (15 min at 42°C). Twenty-four hours after heat stress or exercise, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was maintained for 30-min followed by a 30-min period of reperfusion. Compared with control, both heat-stressed animals and exercised animals (3 and 5 days) maintained higher ( P < 0.05) left ventricular developed pressure (LVDP), maximum rate of left venticular pressure development (+dP/d t), and maximum rate of left ventricular pressure decline (−dP/d t) at all measurement periods during both ischemia and reperfusion. No differences existed between heat-stressed and exercise groups in LVDP, +dP/d t, and −dP/d t at any time during ischemia or reperfusion. Both heat stress and exercise resulted in an increase ( P < 0.05) in the relative levels of left ventricular heat shock protein 72 (HSP72). Furthermore, exercise (3 and 5 days) increased ( P < 0.05) myocardial glutathione levels and manganese superoxide dismutase activity. These data indicate that 3–5 consecutive days of exercise improves myocardial contractile performance during in vivo I/R and that this exercise-induced myocardial protection is associated with an increase in both myocardial HSP72 and cardiac antioxidant defenses.

Attenuation of hepatic ischemia-reperfusion injury through CD47 blockade in vivo

2012 ◽  
Vol 215 (3) ◽  
pp. S138
Author(s):  
Bernard John DuBray ◽  
Pam T. Manning ◽  
William A. Frazier ◽  
Kristen L. Gunter ◽  
Parvathi Balachandran ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

scholarly journals Role of miR-148a in Mitigating Hepatic Ischemia-Reperfusion Injury by Repressing the TLR4 Signaling Pathway via Targeting CaMKIIα in Vivo and in Vitro

2018 ◽  
Vol 49 (5) ◽  
pp. 2060-2072 ◽  
Author(s):  
Daofeng Zheng ◽  
Zhongtang Li ◽  
Xufu Wei ◽  
Rui Liu ◽  
Ai Shen ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hepatic Ischemia ◽  
Tlr4 Signaling ◽  
Hepatic Ischemia Reperfusion

Background/Aims: Hepatic ischemia-reperfusion (I/R) injury, which is mainly induced by inflammation and unstable intracellular ions, is a major negative consequence of surgery that compromises hepatic function. However, the exact mechanisms of liver I/R injury have not been determined. Positive crosstalk with the Ca2+/CaMKII pathway is required for complete activation of the TLR4 pathway and inflammation. We previously found that miR-148a, which decreased in abundance with increasing reperfusion time, targeted and repressed the expression of CaMKIIα. In the present study, we examined the role of the miR-148a machinery in I/R-induced Ca2+/CaMKII and TLR4 signaling changes, inflammation, and liver dysfunction in vivo and in vitro. Methods: Liver function was evaluated by serum aminotransferase levels and hematoxylin-eosin (HE) staining. Inflammatory factors were detected by enzyme-linked immunosorbent assay. Gene and protein expression were assessed by RT-PCR and western blot. Small interfering RNA was used to silence target gene expression. HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to measure hepatic tissue apoptosis. These assays were performed to identify factors upregulated in hepatic I/R injury and downregulated by miR-148a. Results: We manifested that expression of CaMKIIα and phosphorylation of TAK1 and IRF3 were elevated in hypoxia/reoxygenation (H/R)-treated primary Kupffer cells (KCs) and liver tissue of I/R-treated mice, but these effects were attenuated by treatment with miR-148a mimic and were accompanied by the alleviation of liver dysfunction and hepatocellular apoptosis. Luciferase reporter experiments showed that miR148a suppressed luciferase activity by almost 60%. Moreover, knockdown of CaMKIIα in H/R KCs led to significant deficiencies in p-TAK1, P-IRF3, IL-6, and TNF-α, which was consistent with the effects of miR-148a overexpression. Otherwise, the same trend of activation of TAK1 and IRF3 and inflammatory factors in vitro was observed in the siTAK1 + siIRF3 group compared with the siCaMKIIα group. Conclusion: Taken together, we conclude that miR-148a may mitigate hepatic I/R injury by ameliorating TLR4-mediated inflammation via targeting CaMKIIα in vitro and in vivo.

Sign in / Sign up

Export Citation Format

Share Document