Protective effect of tadalafil on ischemia/reperfusion injury of rat ovary

Background/Purpose

The aim of the study was to evaluate the effects of tadalafil (TDF) on ischemia/reperfusion (I/R) injury in rat ovaries.

Methods

Thirty-five female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S), I/R1, I/R2, TDF1, and TDF2. In the I/R1 and TDF1 groups, 3-hour ischemia was followed by 12-hour reperfusion; and in the I/R2 and TDF2 groups, 3-hour ischemia was followed by 24-hour reperfusion. In the TDF groups, 30 minutes before reperfusion, a single dose of 5 mg/kg TDF was administered intraperitoneally. The ovarian tissue levels of malondialdehyde and nitric oxide (NO), and the activities of superoxide dismutase and catalase were measured biochemically. Tissue damage to ovarian tissue was scored by histopathologic examination.

Results

The tissue malondialdehyde levels were significantly higher and the catalase and superoxide dismutase activities were significantly lower in the I/R groups compared with the S and TDF groups (P < .05). The NO levels were significantly higher in the TDF1 group than the S and I/R1 groups (P < .05). Although the NO levels were increased in the TDF2 group compared with the I/R2 group, the difference was not significant. Ovarian tissue damage scores of the I/R groups were significantly higher than those of the S group (P < .05). Treatment with TDF significantly decreased the ovarian tissue damage scores in the TDF groups compared with the I/R groups (P < .05).

Conclusions

Tadalafil is effective in preventing tissue damage induced by I/R in rat ovaries.     

Protective effect of intraperitoneal ozone application in experimental ovarian ischemia/reperfusion injury

AimThe current accepted management of ovarian torsion is ovary-sparing surgery. Ozone therapy is used to reduce ischemia/reperfusion (I/R) injury in several situations. An experimental study was designed to evaluate effect of ozone application in ovarian I/R injury.Materials and methodsThree groups (n = 6) and 18 rats were included in the study. After anesthesia, right ovaries were fixed and removed at the end of 2 hours in sham group (SG). In torsion group (TG), right ovaries underwent 720° torsion in a counterclockwise direction. Ovaries were removed after 2 hours torsion and 2 hours reperfusion. In ozone group (OG), torsion was created by the same technique, and 95% oxygen plus 5% ozone gas mixture was given intraperitoneally (25 μg/mL, 0.5 mg/kg) 10 minutes before reperfusion. After 2 hours reperfusion, ovaries were removed. Histopathologic examination of ovarian and periovarian sections was performed for the presence of congestion (C), hemorrhage, interstitial edema (IE), and polymorphonuclear neutrophilic infiltrations. Tissue samples were analyzed for malondialdehyde, nitric oxide (NO), and total sulphidryl (t-SH) values. Results were compared between 3 groups.ResultsAt histopathologic examination, the TG have elevation in terms of ovarian C, polymorphonuclear neutrophilic infiltration, and periovarian IE when compared with SG (P < ,05). In OG, ovarian C and periovarian IE were reduced according to TG, whereas the increase was observed only in ovarian C compared with SG (P < .05). At biochemical evaluation of oxidative stress markers in SG and TG, there was no difference between them (P < .05). Malondialdehyde levels were significantly lower in OG than TG, whereas NO and t-SH values were higher (P < .05). Malondialdehyde levels were decreased in OG compared with SG (P < .05). However, no difference was observed in NO and t-SH levels (P > .05).ConclusionIntraperitoneal application of ozone creates a positive impact on histologic and biochemical markers on I/R injury owing to ovarian torsion. The ozone application can be developed to support efforts to protect ovary in ovarian torsion.     

Protective effect of erythropoietin on torsion/detorsion injury in rat model

Purpose

The aim of the study is to investigate the effects of erythropoietin on torsion/detorsion injury in rats.

Methods

Forty rats were divided randomly into 5 groups: group I (sham, S), sham operation; group II (torsion/detorsion 1, T/D₁), 3 hours ischemia and 1 hour reperfusion; group III (torsion/detorsion 2, T/D₂), 3 hours ischemia and 48 hours reperfusion; group IV (erythropoietin 1, EPO₁), 3 hours ischemia, 1 hour reperfusion, and a single dose of EPO; and group V (erythropoietin 2, EPO₂), 3 hours ischemia, 48 hours reperfusion, and 2 doses of EPO. Malondialdehyde (MDA) and nitric oxide (NO) levels and activities of superoxide dismutase and catalase were measured. Tissue damage to ovarian tissue was scored by histologic examination. Data were compared among groups with parametric tests.

Results

The MDA levels in the S and EPO groups were significantly lower than the T/D groups (P < .001). Catalase and superoxide dismutase activities, and NO levels in the S and EPO groups were significantly higher than in the T/D groups (P < .05). Ovarian tissue damage in the S and EPO groups was significantly less than in the T/D groups (P < .05). Levels of all biochemical markers and ovarian tissue damage scores were similar among the S, EPO₁, and EPO₂ groups (P > .05).

Conclusion

Erythropoietin attenuates ischemia-reperfusion injury when given during the acute phase of ovarian torsion-detorsion in a rat model.     

The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study

Abstract Objective: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. Methods: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40–50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. Results: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). Conclusion: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.     

Curcumin Nutrition for the Prevention of Mesenteric Ischemia-Reperfusion Injury: An Experimental Rodent Model

Background

Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-κB (NF-κB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats.

Methods

Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α.

Results

There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-α in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05).

Conclusion

This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.     

Activated protein C attenuates intestinal reperfusion-induced acute lung injury: an experimental study in a rat model

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. APC has been shown to attenuate local deleterious effects of ischemia/reperfusion (I/R) injury in many organs. We aimed to investigate the effects of APC on lung reperfusion injury induced by superior mesenteric occlusion. METHODS: Male Wistar-Albino rats were allocated into 4 groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to group 1 except for APC treatment (n = 12); (3) intestinal I/R group, 60 minutes of ischemia followed by 3 hours of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 microg/kg injection of APC intravenously, 15 minutes before reperfusion (n = 12). Evans blue dye was injected into half of the rats in all groups. We assessed the degree of pulmonary tissue injury by measuring activities of oxidative and antioxidative enzymes, as well as nitrate (NO(3)(-))/nitrite (NO(2)(-)) levels, biochemically. We evaluated acute lung injury (ALI) by establishing pulmonary neutrophil sequestration and ALI scoring histopathologically. Pulmonary edema was estimated by using Evans blue dye extravasation and wet/dry ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. RESULTS: APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the lung tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes (P < .05). Pulmonary neutrophil sequestration and ALI scores were decreased significantly with APC administration (P < .05). In addition, APC treatment significantly alleviated pulmonary edema (P < .05). CONCLUSIONS: This study clearly showed that APC treatment significantly attenuated the lung reperfusion injury. Further clinical studies are required to clarify whether APC has a useful role in the reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.     

Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model

Background

Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process.

Methods

Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 μg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 μg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured.

Results

Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05).

Conclusion

This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.     

Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model

Background

Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.

Methods

Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation, each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53, caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry (W/D) weight ratio.

Results

Compared with the saline + sham group, the saline + I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared with the saline + I/R group, sildenafil + I/R group had significant decreases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α level, and W/D weight ratio but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil + sham group, there were significant increases in p53 and TNF-α expression in the sildenafil + I/R group (P < 0.05).

Conclusions

Pretreatment with sildenafil alleviates lung apoptosis and tissue injury in a rat model.     

Comparison of the effects of sodium nitroprusside and L-carnitine in experimental ischemia-reperfusion injury in rats

AIM: The aim of this study was to evaluate the protective effect of sodium nitroprusside (SNP) as a nitric oxide (NO) donor and L-carnitine intraperitoneal administration to treat experimental ischemia-reperfusion (I/R) in rats. MATERIALS AND METHODS: Rats were divided into four groups, each one consisting of 10 animals. Group 1 was subjected to a sham operation. In group 2, an I/R process was applied to the rats. In group 3, SNP (5 mg/kg) and in group 4, L-carnitine (500 mg/kg) was administered in addition to the I/R process. Ileal tissue samples were obtained for analysis of tissue malonyl dialdehyde (MDA) and for histopathologic examination. RESULTS: By histopathologic examination, the I/R group showed a significant difference from the SNP and L-carnitine groups (P<.05). There was no difference between the sham, the SNP, and the L-carnitine groups (P>.05). SNP used as an NO donor produced a significant decrease in MDA levels. There was a significant difference between the MDA levels of the SNP and the I/R groups (P<.05). Also, the difference between this group and the I/R group was significant (P<.05). CONCLUSION: SNP helped to both prevent and reduce mucosal damage in terms of histological and tissue MDA levels. Since the results of the L-carnitine group and the SNP group were similar, L-carnitine was as effective as exogenous NO.     

The Effect of Octreotide on Hepatic Ischemia-Reperfusion Injury in a Rabbit Model

Background

Hepatic ischemic-reperfusion injury (HIRI) is a major cause of morbidity and mortality following liver surgery. Octreotide (Oct) has been reported to improve hepatocellular energy metabolism in a rat HIRI model. This study was designed to evaluate whether Oct could protect the liver of rabbits against ischemic-reperfusion (I/R) injury.

Methods

Twenty-four adult New Zealand rabbits were randomly divided into a sham operated group (Control), an ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1β) levels, and endotoxin (ETX) levels were measured during I/R.

Results

Compared with the Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to the I/R group (P < .05). ALT, AST, LDH, IL-1β, and ETX levels were increased in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the increase was lower in the I/R + Oct group relative to the I/R group (P < .05). Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P < .05) and Bax expression in the I/R group was reduced compared with other groups (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than in the I/R group by microscopy.

Conclusions

Oct pretreatment attenuated hemodynamic changes and decreased liver enzyme changes induced by HIRI in a rabbit model. The protection mechanisms of Oct may be related to reduced ETX levels, down-regulation of the inflammatory cytokines TNFα and IL-1β, and inhibition of hepatocellular apoptosis, as well as the modulation of the mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears that Oct may be useful in decreasing liver injury after liver surgery and/or transplantation and may serve as a promising agent against HIRI.     

α-Lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine

Purpose  Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of α-lipoic acid (α-LA) and ebselen against intestinal I/R injury. Methods  Forty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+α-LA group; an I/R+ebselen group; and an I/R+α-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes. Results  There was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P < 0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+α-LA+ebselen group than in the I/R group (P < 0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups. Conclusion  α-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS.     

Protective effects of clarithromycin in rats with hypoxia/reoxygenation-induced intestinal injury

Background

This study was designed to determine the role of oxidative stress, nitric oxide (NO), and glutathione-related antioxidant enzymes in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury and to evaluate the potential benefits of prophylactic clarithromycin.

Methods

One-day-old Wistar albino rat pups (N = 21) were randomly divided into 3 groups: group I (control), group II (exposed to H/R), and group III (clarithromycin + H/R). Clarithromycin was administered (40 mg/kg) subcutaneously to group III for 3 days. On the fourth day, all rats except controls were exposed to H/R and were killed at 6 hours after H/R. Histopathologic injury scores (HIS), malonyldialdehyde, glutathione (GSH), glutathione-peroxidase (GSH-Px) activities, and NO levels were measured on intestinal samples.

Results

Whereas there was no difference for malonyldialdehyde levels among groups, HIS and NO levels were higher in group II than groups I and III (P < .05). However, GSH and GSH-Px activities were lower in group II than groups I and III (P < .05). Clarithromycin significantly increased GSH and GSH-Px activities and reduced HIS and NO levels in group III.

Conclusion

This study showed that oxidative stress and NO contributed to the pathogenesis of H/R-induced bowel injury and that clarithromycin had a protective effect on bowel injury owing to anti-inflammatory and antioxidant effects.     

Revisiting ischemia and reperfusion injury as a possible cause of necrotizing enterocolitis: Role of nitric oxide and superoxide dismutase

Background/Purpose: The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered a major contributing factor. Nitric oxide (NO) and superoxide dismutases (SODs) have been shown to protect bowel from I/R injury. This study aims to assess (1) the ability of premature intestine to resist I/R injury compared with mature intestine and (2) the possible role of NO and SODs in modulating such response. Methods: Intestines from 5 groups of rats (n = 6 for each study group) were studied: (1) premature, gestational age 20 days; (2) premature, gestational age 22 days; (3) full-term, newborn; (4) infant, day 15; (5) infant, day 30. Experiments: (1) The degrees of I/R injury after 0, 30, 60, 90 and 120 minutes, respectively, of ischemia and 25 minutes of I/R were assessed histologically by a pathologist who was unaware of the operative details. (2) Tissue NO and copper levels were measured by electroparamagnetic resonance (EPR) study; and nitric oxide synthases, copper zinc (CuZn) SODs and manganese (Mn) SODs were examined immunohistochemically. (3) and (4) I/R injury was assessed in rats that had received intraperitoneal injections of L-arginine (NO donor) and L-NAME (NO antagonist), respectively. Results: For premature (1,2), newborn (3) and mature (4,5) intestines, grades of injury at maximum I/R period studied (120 minutes of ischemia, 25 minutes of reperfusion) were 0, 0, and 3, respectively (P [lt ] .05); NO levels were 1 u [plusmn] 1.5, 3 [plusmn] 2.5, and 22 u [plusmn] 3.5, respectively (P [lt ] .05); Cu levels were 150 u [plusmn] 15, 200 u [plusmn] 41 and 12 u [plusmn] 2, respectively (P [lt ] .05); NOS in intestines were +, +, +++ and CuZnSODs were ++, +++, +, respectively; and MnSODs were +++, ++, [minus ], respectively. No change in NO levels was detected in groups (1), (2), or (3) after L-arginine and L-NAME injections. Conclusions: Premature rat intestine is highly resistant to I/R injury, which may indicate that I/R alone, in the absence of other predisposing factors (eg, bacterial colonization) may not be sufficient in causing NEC. Nitric oxide does not have a protective role for immature and newborn intestines in I/R as in mature intestine. The high level of SODs of the immature and newborn intestine may play an important role in its high resistance to I/R injury. J Pediatr Surg 37:828-834.     

Hyperbaric Oxygen Therapy Alleviates Oxidative Stress and Tissue Injury in Renal Ischemia/Reperfusion Injury in Rats

Hyperbaric oxygen (HBO) therapy has been shown to attenuate renal ischemia/reperfusion (I/R) injury in rats, when applied in the early reperfusion period. The aim of this study was to elucidate possible beneficial effects of HBO therapy on renal I/R injury, when applied 24 h after ischemia. Rats were randomized into three groups: (1) control group (n = 20), (2) I/R group (n = 20), and (3) I/R + HBO group (n = 20). Renal I/R injury was created by interrupting renal blood flow for 30 min with a non-traumatic vascular clamp. HBO therapy was administered 24 h after I/R injury and continued for 5 days. At the end of the study, rats were sacrificed under anesthesia, blood was drawn, and right kidneys were harvested for analysis. Renal I/R injury increased serum and tissue malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. HBO therapy attenuated MDA levels by increasing SOD and GPx activities. HBO therapy also prevented neutrophil infiltration and tissue injury in kidneys. Taken together, HBO therapy has been found to be effective in the delayed period of I/R injury.     

Lisinopril inhibits endothelin-1 in the early period of hepatic reperfusion injury in a partial hepatectomy model

Background

Ischemia-reperfusion (I/R) injury is a major problem during liver surgery. We investigated the effects of lisinopril, an angiotensin-converting enzyme inhibitor, in the early postoperative period of reperfusion injury after Pringle's maneuver during an 80% partial hepatectomy (PH) in rats.

Methods

Four groups of male Sprague-Dawley rats were studied: Group 1 (n = 10), sham laparotomy; group 2 (n = 10), PH without portal occlusion; group 3 (n = 10), PH with portal pedicle clamping; group 4 (n = 15), same as group 3 with additional intravenous lisinopril preconditioning (1 mg/kg⁻¹). We analyzed superoxide radical (O₂⁻), nitric oxide (NO), peroxynitrite (ONOO⁻) levels in the liver tissue and blood levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1).

Results

ALT and ET-1 levels were progressively increased in group 2 (P > .05) versus group 3 (P < .001 and P < .05), showing hepatocellular damage due to I/R injury in the remnant liver, although histopathologic changes were unremarkable at this early stage. The levels of ALT and ET-1 decreased with lisinopril precontioning in group 4 compared with group 2 (P > .05 and P < .01) or group 3 (P < .05 and P < .001). O₂⁻ levels were increased significantly in groups 2 and 3 (P < .01 for both). O₂⁻ level in Group 4 was remarkably decreased albeit not significant compared with the other groups. NO and ONOO⁻ levels were also significantly greater in groups 2 (P < .01 and P < .05) and 3 (P < .001 and P < .01). These levels were decreased significantly among group 4 compared with group 3 (P < .05), a decline almost to the level of group 1 (P > .05).

Conclusion

In the early postoperative period of an extended hepatectomy model, Pringle's maneuver causes I/R increasing the insult to the remnant liver. Lisinopril preconditioning alleviated I/R injury by decreasing the O₂⁻, NO, ONOO⁻, ET-1, and ALT levels, thereby exerting a protective role on the remaining liver.     

Comparison of Inflammatory Markers Between the Sevoflurane and Isoflurane Anesthesia in a Rat Model of Liver Ischemia/Reperfusion Injury

BackgroundSevoflurane and isoflurane had been reported to improve ischemia/reperfusion injury (I/R) through amelioration of the inflammatory response. We aimed to explore and compare the molecular mechanisms involved in sevoflurane and isoflurane anesthesia in liver ischemia-reperfusion of rat model.MethodsForty male Wistar rats were randomly divided into 4 groups: sham group, I/R group, sevoflurane group, and isoflurane group. The liver I/R injury model was established to investigate the effect of sevoflurane and isoflurane anesthesia on liver ischemia/reperfusion. The inflammatory markers and complement C3, C5a, and C6 were detected by enzyme-linked immunosorbent assay. Oxidative stress was detected by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO).ResultsOur results showed that sevoflurane anesthesia significantly decreased alanine transaminase, aspartate transaminase, and lactate dehydrogenase levels compared with isoflurane and controls. Sevoflurane inhibited I/R injury induced production of tumor necrosis factor α, interleukin 1, interleukin 6, and intercellular cell adhesion molecule-1 and promoted interleukin 10 production more significantly compared with isoflurane. Reduced MDA and NO and elevated SOD release suggested that oxidative stress was attenuated by sevoflurane and isoflurane anesthesia. Both sevoflurane and isoflurane anesthesia significantly decreased plasma C3 levels compared with the I/R injury group without differences.ConclusionSevoflurane anesthesia produced a more significant inhibitive effect on inflammatory cytokines and oxidative stress in liver I/R injury model than isoflurane, suggesting that sevoflurane is more suitable in surgery.     

Effect of Seed of Cassia tora Extract in the Prevention of Remote Renal Reperfusion Injury

ObjectiveRenal ischemia/reperfusion (I/R) injury is characterized by the acute deterioration of renal function during ischemia and renal inflammation. Cassia tora has various effects, including antioxidant, antidiabetic, and hypolipidemic properties. In the present study, we investigated whether C tora has a renoprotective effect on I/R-induced acute kidney injury in rats.MethodsWe fed Sprague-Dawley rats either C tora (100 mg/kg/d) or saline. One week later, ischemia was induced by bilateral renal pedicle occlusion for 30 minutes, followed by reperfusion. Rats were randomized into 3 major groups, which were treated as follows: 1. the sham operation group; 2. the I/R group; and 3. the I/R-C tora group.ResultsCompared to the sham group, the I/R group had higher levels of blood urea nitrogen and serum creatinine in serum and lower expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, and nitric oxide. Compared to the I/R group, the I/R-C tora group had higher expression of catalase, superoxide dismutase, glutathione peroxidase, antioxidant, and nitric oxide, as well as lower levels of blood urea nitrogen and creatinine in serum.ConclusionsThese results suggest that C tora has significant therapeutic effects in ischemic renal injury.     

Involvement of endothelin/ nitric oxide balance in hepatic ischemia/ reperfusion injury

Introduction: Endothelin (ET) and nitric oxide (NO) act as opponents in the regulation of the hepatic microcirculation. During ischemia/reperfusion (I/R) ET levels are increased, whereas no rise in NO levels is observed. This imbalance may be responsible for microcirculatory disturbances. The aim of this study was to restore the delicate ET/NO balance to maintain the integrity of the hepatic microcirculation and to reduce I/R injury. Methods: Ischemia was induced by crossclamping of the hepatoduodenal ligament for 30 min with portal decompression using a splenocaval shunt (56 Wistar rats, 200–250 g). Sham operation, ischemia and treatment groups with the endothelin receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor l-arginine (400 mg/kg body weight i.v.) were performed. For assessment of the microcirculation, sinusoidal perfusion rate, diameters of sinusoids and postsinusoidal venules, leukocyte endothelium interactions and velocity of free-flowing leukocytes were investigated by means of in vivo microscopy 30–90 min after reperfusion. Local hepatic tissue pO₂ was measured prior to ischemia, 30 min and 60 min after reperfusion and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels were investigated 2 h and 6 h after reperfusion. Results: After ischemia, sinusoidal and venular diameters were reduced to 76% and 85%, respectively, of sham operation group values (P<0.05), but were maintained at baseline in ERA (98/102%) and NO (102/105%) groups (P<0.05). Increased postischemic leukocyte sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/ 324% (NO), respectively (P<0.05). Perfusion rate was increased to 93% and 94% compared with 82% in the ischemia group (P<0.05). Concomitant with the improved microcirculation in therapy groups, local hepatic tissue pO₂ was improved 30 min after reperfusion in the ERA (11.0 mmHg) and the l-arginine group (11.5 mmHg) relative to the ischemic group (6.9 mmHg) (P<0.05). In addition, postischemic AST/ALT increase was reduced by therapy. Conclusion: Our results indicate that maintenance of ET/NO balance by blocking ET receptors, as well as providing a NO donor, protects the liver microcirculation and reduces hepatic I/R injury. Received: 14 August 1998 Accepted: 13 October 1998     

The effect of zinc aspartate pretreatment on ischemia-reperfusion injury and early changes of blood and tissue antioxidant enzyme activities after unilateral testicular torsion-detorsion

Background/purpose

The aim of this study is to investigate the effect of zinc aspartate (ZA) pretreatment on ischemia-reperfusion (I/R) injury and blood and tissue antioxidant enzyme activity early after unilateral testicular torsion-detorsion (T/D).

Methods

Forty prepubertal male Sprague-Dawley rats (weight 160 to 220 g) were divided into 4 groups each containing 10 rats. Surgery was conducted under intraperitoneal 1-shot ketamine (50 mg/kg) anesthesia. The scrotum was entered through a midline incision. Rotating the left testis 720° in a clockwise direction was the model of the testicular torsion. Group 1 was for the basal values. Group 2 had 4 hours T/D. Group 3 also had 4 hours T/D and pretreated with 50 mg/kg intraperitoneal ZA injection half an hour before detorsion. Group 4 was designed as a sham group. In the Group 2 and Group 3, the tunica vaginalis was opened, and left testicles were rotated clockwise 720° and maintained in this torsion position by fixing with a silk suture to the scrotal wall. The scrotum was closed and 4 hours later reentered for testicular detorsion. After spermatic cord detorsion, the scrotum was closed. At the end of 4 hours detorsion period, bilateral orchiectomies were performed, and 5-mL intracardiac blood samples were taken. Blood and tissue superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) levels were measured, and histopathologic examination was performed.

Results

Group 2 and group 3 had decreased blood SOD and CAT activities and elevated MDA levels indicating I/R injury. The 2 groups were also different from each other for these parameters reflecting the beneficial effect of ZA pretreatment (P < .05). The decreased ipsilateral tissue SOD and CAT activities in group 2 were different from the other groups including group 3 (P < .05). Ipsilateral tissue MDA levels of both group 2 and group 3 were elevated. Group 2 had higher values than group 3 (P < .05). In addition, specimens from group 2 had a significantly greater histologic injury than group 3 (P < .05). These findings were also supporting the beneficial effect of ZA pretreatment. All measurements of contralateral tests were similar to the basal values for all groups (P > .05).

Conclusions

ZA pretreatment reduces I/R injury by its antioxidant effects after unilateral testicular T/D and affects the antioxidant enzyme systems.