Does methylene blue attenuate inflammation in nonischemic lungs after lung transplantation?

ABSTRACT Objective: To evaluate whether methylene blue (MB) could minimize the effects of ischemia-reperfusion injury in the nonischemic lung on a lung transplantation rodent model. Methods: Forty female Sprague-Dawley rats were divided into 20 donors and 20 recipients. The 20 recipient rats were divided into two groups (n = 10) according to the treatment (0.9% saline vs. 1% MB solutions). All animals underwent unilateral lung transplantation. Recipients received 2 mL of saline or MB intraperitoneally prior to transplantation. After 2 h of reperfusion, the animals were euthanized and histopathological and immunohistochemical analyses were performed in the nonischemic lung. Results: There was a significant decrease in inflammation-neutrophil count and intercellular adhesion molecule-1 (ICAM-1) expression in lung parenchyma were higher in the saline group in comparison with the MB group-and in apoptosis-caspase-3 expression was higher in the saline group and Bcl-2 expression was higher in MB group. Conclusions: MB is an effective drug for the protection of nonischemic lungs against inflammation and apoptosis following unilateral lung transplantation in rats.

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Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.4.1828 ◽

2001 ◽

Vol 91 (4) ◽

pp. 1828-1835 ◽

Cited By ~ 60

Author(s):

Nicole Stupka ◽

Peter M. Tiidus

Keyword(s):

Muscle Damage ◽

Ischemia Reperfusion Injury ◽

Serum Insulin ◽

Ischemia Reperfusion ◽

Neutrophil Infiltration ◽

Female Rats ◽

Protective Effects ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

17Β Estradiol

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.

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Hepatic Stellate Cells Play a Functional Role in Exacerbating Ischemia-Reperfusion Injury in Rat Liver

European Surgical Research ◽

10.1159/000499750 ◽

2019 ◽

Vol 60 (1-2) ◽

pp. 74-85 ◽

Cited By ~ 2

Author(s):

Tomokazu Takahashi ◽

Masato Yoshioka ◽

Hiroshi Uchinami ◽

Yasuhiko Nakagawa ◽

Naohiko Otsuka ◽

...

Keyword(s):

Rat Liver ◽

Hepatic Stellate Cells ◽

Functional Role ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Stellate Cells ◽

Treated Group ◽

Sprague Dawley ◽

Perfusion Rate ◽

Sprague Dawley Rats

Purpose: The involvement of hepatic stellate cells (HSCs) with ischemia-reperfusion (I/R) injury in rat liver was examined using gliotoxin, which is known to induce HSC apoptosis. Methods: Male Sprague-Dawley rats were used. HSC was represented by a glial fibrillary acidic protein (GFAP)-positive cell. Liver ischemia was produced by cross-clamping the hepatoduodenal ligament. The degree of I/R injury was evaluated by a release of aminotransferases. Sinusoidal diameter and sinusoidal perfusion rates were examined using intravital fluorescence microscopy. Results: Gliotoxin significantly decreased the number of GFAP-positive cells 48 h after dosing (2.50 ± 0.19% [mean ± SD] in the nontreated group vs. 1.91 ± 0.46% in the gliotoxin-treated group). Liver damage was significantly suppressed by the pretreatment with gliotoxin. Sinusoidal diameters in zone 3 were wider in the gliotoxin group (10.25 ± 0.35 µm) than in the nontreated group (8.21 ± 0.50 µm). The sinusoidal perfusion rate was maintained as well in the gliotoxin group as in normal livers, even after I/R. Conclusions: Pretreatment with gliotoxin significantly reduced the number of HSCs in the liver and further suppressed liver injury following I/R. It is strongly suggested that HSCs play a functional role in exacerbating the degree of I/R injury of the liver.

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Hesperidin Ameliorates Hepatic Ischemia-Reperfusion Injury in Sprague-Dawley Rats

Transplantation Proceedings ◽

10.1016/j.transproceed.2019.02.059 ◽

2019 ◽

Vol 51 (8) ◽

pp. 2828-2832 ◽

Cited By ~ 1

Author(s):

Hyun-Kyung Park ◽

Sang Wook Kang ◽

Min-Su Park

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Sprague Dawley ◽

Hepatic Ischemia ◽

Sprague Dawley Rats ◽

Hepatic Ischemia Reperfusion

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The effects ofN-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet

Hepatology ◽

10.1002/hep.510260320 ◽

1997 ◽

Vol 26 (3) ◽

pp. 670-678 ◽

Cited By ~ 1

Author(s):

H Nakano ◽

H Nagasaki ◽

A Barama ◽

K Boudjema ◽

D Jaeck ◽

...

Keyword(s):

Monoclonal Antibody ◽

Reperfusion Injury ◽

Adhesion Molecule ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Deficient Diet ◽

Steatotic Liver

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L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.6.g1341 ◽

1998 ◽

Vol 275 (6) ◽

pp. G1341-G1352 ◽

Cited By ~ 19

Author(s):

Surinder S. Yadav ◽

David N. Howell ◽

Wenshi Gao ◽

Douglas A. Steeber ◽

Robert C. Harland ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Leukocyte Adhesion ◽

Ischemia Reperfusion ◽

Mutant Mice ◽

Intercellular Adhesion Molecule ◽

Wild Type ◽

Intercellular Adhesion Molecule 1 ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion

Leukocytes recruited during ischemia-reperfusion to the liver are important mediators of injury. However, the mechanisms of leukocyte adhesion and the role of adhesion receptors in hepatic vasculature remain elusive. L-selectin may critically contribute to injury, priming adhesion for later action of intercellular adhesion molecule-1 (ICAM-1). Paired experiments were performed using mutant mice (L-selectin −/−, ICAM-1 −/−, and L-selectin/ICAM-1 −/−) and wild-type mice (C57BL/6) to investigate leukocyte adhesion in the ischemic liver. Leukocyte adhesion and infiltration were assessed histologically. Aspartate aminotransferase levels were significantly reduced (2- to 3-fold) in mutant vs. wild-type mice in most groups but most significantly after 90 min of partial hepatic ischemia. Leukocyte adhesion was significantly reduced in all mutant mice. Areas of microcirculatory failure, visualized by intravital microscopy, were prevalent in wild-type but virtually absent in L-selectin-deficient mice. After total hepatic ischemia for 75 or 90 min, survival was better in mutant L-selectin and L-selectin/ICAM-1 mice vs. wild-type mice and ICAM-1 mutants. In conclusion, L-selectin is critical in the pathogenesis of hepatic ischemia-reperfusion injury. Poor sinusoidal perfusion due to leukocyte adhesion and clot formation is a factor of injury and appears to involve L-selectin and ICAM-1 receptors.

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