Re-Protective Effects of Pre- and Post-Laparoscopy Conditioning,Zinc, Pentoxifylline,and N-acetylcysteine in an Animal Model of Laparoscopy-Induced Ischemia/Reperfusion Injury of the Kidney

Background. Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic hypoperfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. Aim. This study investigated the effects of pre- and post-laparoscopic conditioning, zinc, pentoxifylline (PTX), and N-acetylcysteine (NAC) on markers of I/R injury in an animal model. Methods. Sprague-Dawley male rats (n?=?56, weight range 300–350 g) were randomly placed in one of seven treatment groups. Except for group C (control group who underwent a sham operation without pneumoperitoneum), pneumoperitoneum was created in all using CO₂ insufflation under a pressure of 15 mmHg. Group L (laparoscopy) was subjected to 60 min of pneumoperitoneum. Group Lpre (laparoscopic preconditioning plus laparoscopy) was subjected to 5 min of insufflation and 5 min of desufflation followed by 60 min of pneumoperitoneum. Group Lpost (laparoscopy plus laparoscopic post-conditioning) was subjected to 60 min of pneumoperitoneum and 60 min of desufflation followed by 5 min of insufflation and 5 min of desufflation. The laparoscopy plus zinc (LZ), PTX (LP), and NAC (LNAC) groups received a single intraperitoneal injection of zinc (50 mg/kg), pentoxifylline (50 mg/kg), or N-acetylcysteine (150 mg/kg) 5 min before the desufflation period. Animals were sacrificed at the end of the experiments, and kidney samples were tested for malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Results. MDA levels, as an indicator of oxidative stress in kidney tissue samples, were significantly higher in all pneumoperitoneum groups compared to Group C, except for Group Lpre. The pattern of change in tissue levels of SOD, GPX, and catalase was variable in the different treatment groups. Conclusions. In this animal model of renal ischemia/reperfusion injury, laparoscopy caused renal ischemia as evidenced by elevated markers of tissue ischemia-reperfusion injury. This effect was significantly attenuated by post-laparoscopy conditioning, zinc, pentoxifylline, and N-acetylcysteine, but not by pre-laparoscopy conditioning.     

Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model

Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T‐shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty‐four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia.     

An animal model of ischemic priapism and the effects of melatonin on antioxidant enzymes and oxidative injury parameters in rat penis

This experimental study was designed to produce ischemia–reperfusion (I/R) injury in rat corpus cavernosum by inducing 1 h of priapism and investigating the effects of melatonin on the levels of oxidative injury parameters. Twenty-one adult male rats were randomly divided into three groups as follows; sham operated, control group (Group C): only penectomy was performed and blood (3 ml) drawn from vena cava inferior (VCI), ischemia and reperfusion group (Group I/R); priapism (1 h) + ½ h reperfusion + penectomy + blood from VCI, melatonin treatment group (Group I/R + M); priapism (1 h) + melatonin (½ h before reperfusion, 50 mg/kg, ip) + ½ h reperfusion + penectomy + blood from VCI. Priapism was induced with a vacuum erection device (cut tip of 2-cc syringe) and a rubber band was placed at the base of the erect penis. In two groups, excluding Group C, penectomies were performed after 1 h of ischemic priapism and ½ h reperfusion for biochemical analysis of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and protein carbonyl (PC) in the tissues. In all groups, about 3 ml blood was drawn from VCI to study the same parameters in systemic circulation. The results were compared statistically using one-way analysis of variance (ANOVA). As a result, in biochemical examination of penile tissues, there were significant increase in SOD, CAT activities and MDA levels in I/R group in comparison with group C (P < 0.05). With melatonin treatment, these levels were decreased closer to control levels (P < 0.05). The changes in PC levels were insignificant in penile tissues of all groups (P > 0.05). Analysis of serum in all rats revealed that the activity of SOD and the levels of MDA, NO and PC were increased in I/R group when compared with control group but with multiple comparisons only the increases in SOD activity and NO level were significant (P < 0.05). Decrease in the activity of SOD and the levels of NO and PC were significant after melatonin administration in serum of all groups (P < 0.05). The results of this study showed that experimentally induced priapism caused oxidative injury in cavernosal tissues of rats, and treatment with melatonin alleviated these effects. From the result of this experimental study, it can be extrapolated that melatonin may be used as an antioxidant agent in the treatment of ischemic priapism in the future urology practice.     

Protective effects of dexmedetomidine on ischaemia-reperfusion injury in an experimental rat model of priapism

The study aimed to investigate the effects of dexmedetomidine against ischaemia-reperfusion injury occurring after priapism in a model of induced-priapism in rats. A total of 18 male rats were randomised into three groups. Group 1 was the control group. A priapism model was performed rats in Group 2 and then ischaemia-reperfusion injury was evaluated. Group 3 had similar procedures to the rats in Group 2. Rats in Group 3 additionally had 100 μg/kg dexmedetomidine administered intraperitoneally immediately after reperfusion. Blood and tissue samples were analysed. Biochemical analysis of blood samples revealed a decrease in the levels of the pro-inflammatory cytokines including interleukin-1 beta (IL-1 Beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) in Group 3 compared to Group 2 (p:.04, p:.009 and p:.009, respectively). Similarly, the highest malondialdehyde (MDA) level was in Group 2 (p:.002). The levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were significantly higher in Group 3 than that of Group 2 (p:.037 and p:.045, respectively). Direct microscopic examinations revealed positive changes in desquamation, oedema, inflammation and vasocongestion scores in Group 3 compared to Group 2 (p:.007, p:.008, p:.007 and p:.006, respectively). Dexmedetomidine has a protective effect against ischaemia-reperfusion injury in penile tissue.     

Pretreatment with Pentoxifylline and N-Acetylcysteine in Liver Ischemia Reperfusion-Induced Renal Injury

Background and Aims: Acute hepatic injury causes systematic inflammatory responses which may finally lead to functional disturbances in remote organs. In this study, the effects of an inhibitor of inflammatory cytokines (pentoxifylline, PTX) and a well-known antioxidant, N-acetylcysteine (NAC), were evaluated on renal damage and oxidative stress following liver ischemia reperfusion (IR). Method: Five groups of six male rats were used. Group 1 was sham operated. In group 2, 90 min liver partial ischemia was induced by a clamp around both hepatic artery and portal vein and then followed by 4 h of reperfusion. In groups 3 and 4, PTX or NAC was injected intraperitoneally before the ischemia, while in group 5 both drugs were co-administered. The levels of alanine amino-transferase (ALT), aspartate amino-transferase (AST), blood urea nitrogen (BUN), and creatinine in serum as well as malonyldialdehyde (MDA) and glutathione (GSH) levels and morphological changes in renal tissues were assessed. Results: Significant increase in the serum levels of ALT and AST in IR group is indicative of liver functional damages. Elevated BUN and renal tissue MDA, decreased GSH levels, and morphological damages in IR group demonstrate a significant kidney injury and oxidative stress comparing to sham group. Administration of PTX alone and PTX + NAC prevented the IR-induced increase in renal MDA levels. Administration of both drugs and their co-administration prevented the reduction in renal GSH levels and morphological changes. Conclusion: Pretreatment with PTX and NAC before liver IR may be useful to ameliorate renal oxidative damage by preservation of cellular GSH concentration and a reduction in MDA levels.     

Protective Effect of Infliximab on Ischemia/Reperfusion-Induced Damage in Rat Kidney

Objective: To investigate the protective effect of infliximab on ischemia–reperfusion (I/R) injury of the rat kidney. Methods: Twenty-eight male Wistar albino rats were divided into four groups: sham-operated, I/R, I/R with infliximab administered before ischemia [I/R + infliximab (bi)], and I/R with infliximab administered before reperfusion [I/R + infliximab (br)]. After a right nephrectomy to produce damage, the left renal vessels were occluded for 60 min, followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin–eosin (H&E)-stained and periodic acid–Schiff (PAS) sections. Results: The MDA and MPO levels in the I/R group were significantly higher than in the other groups (p < 0.05), and the SOD and GSH levels in the I/R + infliximab (bi) and I/R + infliximab (br) groups were significantly higher than in the I/R group (p < 0.05). However, histological examination revealed that the I/R + infliximab (bi) group and the I/R + infliximab (br) group had significantly fewer tubular changes and interstitial inflammatory cell infiltration than the I/R group. Conclusion: These results show that infliximab may protect against I/R injury in the rat I/R model.     

The effect of pentoxifylline on penile cavernosal tissues in ischemic priapism-induced rat model

Introduction

Priapism is defined as persisting (>4 h), painful and abnormal tumescence that can occur without sexual stimulation. Three subtypes priapisms are seen—the non-ischemic priapism, intermittent and the ischemic priapism. In ischemic priapism, there is an abnormality in the veno-occlusive mechanism, resulting in venous stasis and accumulation of deoxygenated blood within the penile cavernosal tissue. Cavernosal tissue necrosis develops after extended period of ischemia and is eventually replaced by fibrotic tissue. It may results in erectile dysfunction if not treated promptly. Although, standard treatment of the ischemic priapism is penile aspiration and intracavernosal alpha-adrenergic agents, new oral agents have been investigated to reduce the cavernosal damage. In this study, the effect of different doses of pentoxifylline on cavernosal tissues was evaluated.

Materials and methods

Thirty-six male Wistar albino rats, age 5.5–6 months and weighing 250–300 g, were used in this study. The rats were randomly divided into five groups. In Group 1 (n = 7), the control group, only penectomy was performed. In Group 2 (n = 8), after 1 h of ischemic priapism, penectomy was performed. Group 3 (n = 7) received daily a 10 mg oral pentoxifylline for 4 weeks after 1 h of ischemic priapism, group 4 (n = 7) received a daily 30 mg oral pentoxifylline for 4 weeks after 1 h of ischemic priapism, and group 5 (n = 7) received a daily 100 mg oral pentoxifylline for 4 weeks after 1 h of ischemic priapism. At the completion of a 4-week period, penile tissues were obtained. Before penile tissues were obtained, intracavernosal pressures measured with electrical field stimulation and smooth muscle collagen ratio were evaluated pathologically.

Results

Electrical field stimulation-induced intracavernosal relaxation decreased in group 2 compared with group 1 (p < 0.05). Electrical field stimulation-induced relaxation enhanced in the group 3, 4 and 5 compared to group 2 (p < 0.05). In group 2, the collagen density was significantly higher than group 1. Administration of pentoxifylline reduced the collagen density caused by ischemic priapism in groups 3, 4 and 5 compared with group 2.

Conclusion

The results of the present study showed that ischemic priapism caused damage in the penile tissues of rats, and treatment with pentoxifylline reduced the harmful effects of ischemic priapism.     

Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation

Background/PurposeThe aim of the study was to evaluate the effects of selenium (Se) on ischemia/reperfusion (I/R) injury in rat ovaries.MethodsThirty-five female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S), I/R1, I/R2, Se1, and Se2. In the I/R1 and Se1 groups, 4 hours of ischemia was followed by 6 hours of reperfusion, and in the I/R2 and Se2 groups, 4 hours of ischemia was followed by 12 hours of reperfusion. In the Se groups, 30 minutes before reperfusion, a single dose of 0.2 mg/kg Se was administered intraperitoneally. The ovarian tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. Tissue damage to ovarian tissue was scored by histopathologic examination.ResultsThe I/R groups had significantly higher MDA levels and lower CAT, SOD, and GPx activities than the sham group (P < .05). Although NO levels were significantly higher in the I/R1 group than in the sham group (P < .05), the NO levels in the I/R2 and sham groups were similar. Selenium pretreatment significantly lowered tissue MDA and NO levels and increased tissue SOD and GPx activities in the Se groups, compared with those in the I/R groups (P < .05). Catalase activities were significantly higher in the Se2 group than in the I/R2 group (P < .05). Catalase activities were higher in the Se1 group than in the I/R1 group, but the difference was not statistically significant. Treatment with Se significantly decreased the ovarian tissue damage scores in the Se2 group compared with those in the I/R2 group (P < .05).ConclusionSelenium is effective in preventing tissue damage induced by I/R in rat ovaries.     

The Effect of Diosmin Hesperidin on Intestinal Ischaemia — Reperfusion Injury

Aim: The effect of Diosmin Hesperidin on intestinal ischaemia reperfusion injury was evaluated in an experimental model in rats.

Material and methods: Forty Spraque-Dawley rats were divided into 4 groups of (n = 10) (sham, sham + Diosmin Hesperidin, Reperfusion, Reperfusion + Diosmin Hesperidin). Diosmin Hesperidin oral gavage was administrated at a dose of 50 mg/kg to rats 14 and 2 hours before the operation and 30 minutes of ischaemia and 30 minutes of reperfusion was performed in the groups when appropriate. Ileum samples were resected for histopathological evaluation and tissue malondialdehyde (MDA) and myeloperoxidase (MPA) level determination.

Results: Mean mucosal injury score of IR group (4,50 ± 0,23) was significantly higher than the other groups (p < 0.05). Although mean mucosal injury score of IR + DH group was higher than sham and sham + DH groups, difference was not statistically significant (p > 0.05). Tissue MDA and MPO activities of IR group were 45,55 ± 2.61 nmol/g/wet tissue and 1.68 ± 0.25 U/g/wet tissue respectively and were significantly higher than the other groups (p < 0.008). Although tissue MDA and MPO activities of IR + DH group was higher than sham and sham + DH groups, differences were not statistically significant (p > 0.008).

Conclusion: Diosmin Hesperidin seems to be effective in the prevention of intestinal reperfusion injury.     

Antioxidative status and lipid peroxidation in kidney tissue of rats fed with vitamin B6-deficient diet

Introduction: The aim of this study was to evaluate lipid peroxidation (LP) and free radical scavenging enzyme activities in kidney tissue of vitamin B₆-deficient rats. Material and Methods: The rats were divided into control and vitamin B₆-deficient groups. After 4 weeks of feeding, animals in all groups were anesthetized by thiopental sodium (50 mg/kg). Thoraces were opened, 2 mL blood samples were taken from aortas, then the rats were killed by cervical dislocation, and kidney tissues were removed. Biochemical measurements in kidney tissue were carried out using a spectrophotometer. Results: Total superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), superoxide dismutase (SOD) activities, and antioxidant potential (AOP) values in the vitamin B₆-deficient group were significantly lower than those of the control group, whereas glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST) activities, and malondialdehyde (MDA) level were significantly higher than those of the control group (p < 0.05). Discussion: The results show that vitamin B₆ deficiency causes an attenuation in antioxidant defense system and an increase in oxidative stress in kidney tissue of rats.     

Effects of mexiletine,ginkgo biloba extract (EGb 761), and their combination on experimental head injury

Lipid peroxidation (LP) and brain edema are important factors that produce tissue damage in head injury. The purpose of this study was to investigate the effect of mexiletine, gingko biloba extract (EGb 761), and their combination on LP and edema after moderate head trauma. Forty rats were randomly and blindly divided into four groups of ten animals each: control group (bolus injection of physiological saline), mexiletine group (50 mg/kg per injection), EGb 761 group (30 mg/kg per injection), and mexiletine plus EGb 761 group (50 mg/kg and 30 mg/kg per injection, respectively). The injections were given intraperitoneally at 1 h, 9 h, and 17 h after trauma. Twenty-four hours after injury, the rats were killed, and malondialdehyde (MDA) levels and brain water content were determined. Rats treated with mexiletine, EGb 761, and mexiletine plus EGb 761 had significantly lower MDA levels than the control group (P<0.01). The lowest MDA levels were measured in the mexiletine plus EGb 761 group. However, there was no significant difference in brain water content between treated groups and the control group (P>0.05). These findings show the usefulness of mexiletine and its combination with EGb 761 as a cerebroprotective agent in this model of experimental head injury.     

Carnitine as a preventive agent in experimental renal ischemia-reperfusion injury

Reactive oxygen species generated during the reperfusion of ischemic kidney, as well as any other tissue, cause lipid peroxidation damaging the cell membrane. The aim of this study was to investigate the effect of carnitine in reperfusion injury of the kidney. Male albino rabbits were subjected to unilateral renal 1-h warm ischemia followed by 15 min of reperfusion. Group I (n=9): control group received 3 cc of isotonic saline solution and group II (n=9): carnitine group received 100 mg/kg of carnitine. Blood samples were collected at the 15th min of reperfusion from the left renal vein selectively. Preischemic and post-reperfusion serum and renal tissue MDA levels were measured by thiobarbituric acid reactive substances (TBARS) spectrophotometric analysis. The preischemic serum and tissue MDA values (sham values) for groups I and II were statistically comparable (P > 0.01). Serum and tissue MDA levels were markedly elevated after 15 min of reperfusion in group I (P < 0.01), while the values remained in the baseline levels following reperfusion in group II (P > 0.01). In group I, the major histological differences observed in the reperfused kidneys were marked edema and congestion whereas glomerular and tubular cellular integrity were well preserved in group II. Pre-treatment with carnitine in solid organ transplantations, preschock states, surgical procedures that require temporary vascular clamping etc. may be helpful to minimize the reperfusion injury in the involved tissue, reducing morbidity and mortality. Received: 22 May 2000 / Accepted: 1 February 2001     

Renal remodelling in dietary protein modified rat polycystic kidney disease

Dietary protein restriction slows progression of the Han:SPRD-cy rat model of polycystic kidney disease. We undertook studies to examine the relative changes in interstitial and tubular pathology as a result of feeding an 8% casein (LP) diet to Han:SPRD-cy rats. Archival tissue from a previous study comparing LP and 20% casein (NP) diets was examined morphometrically after immunohistochemical or histochemical staining for apoptosis, proliferation antigens, interstitial fibrosis, and macrophage infiltration. Expression of common extracellular matrix genes was measured by Northern analysis. Animals fed LP diet demonstrated reduced tubular epithelial remodelling compared with animals fed NP diet by both proliferating cell nuclear antigen-positive cells (57.5 vs. 71.6 cells/mm epithelium, P=0.007) or apoptosis (31.2 vs. 35.6 cells/mm epithelium, P=0.006). Interstitial pathology demonstrated that LP feeding was associated with proportionately greater reductions in interstitial fibrosis (0.3 vs. 1.3 ml/kg body weight, P=0.003), interstitial cellularity (361 vs. 604 cells/high-power field, P=0.0002), and interstitial macrophages (67 vs. 149 cells/high-power field, P=0.0002). Northern analysis only revealed significantly lower levels of monocyte chemoattractant protein mRNA (P=0.04) in animals fed the LP diet. Dietary protein restriction modifies both tubule and interstitium, with significant impact upon interstitial inflammation and fibrosis in the Han:SPRD-cy rat. Received: 24 April 1998 / Revised: 10 November 1998 / Accepted: 11 November 1998     

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.     

Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia-reperfusion injury in rats

Trimetazidine (TMZ), a potent antioxidant agent, has been used to protect the myocardium, liver and kidney from ischemia reperfusion (IR) injury. We investigated the effect of TMZ, a cellular anti-ischemic agent and a free radical scavenger, on 60 min of warm intestinal IR injury in rats. Sprague-Dawley rats were divided into three groups: a sham-operated group (no IR injury, n = 8), an ischemic control group (control, n = 8), and a TMZ-treated group (3 mg/kg, n = 8). Malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and mucosal damage were investigated after 120 min of reperfusion. MDA levels and MPO activity were more elevated and histopathological damage more severe in the control group than in the sham group (P < 0.05). MDA levels and MPO activity were lower and there was less histopathological damage in the TMZ group than in the control group (P < 0.05). Accumulation of lipid peroxidation products and neutrophils in mucosal tissues were significantly inhibited by TMZ treatment. We conclude that pretreatment of rats with TMZ before intestinal ischemia attenuates but does not prevent, histological damage. Received: 7 May 1998 Received after revision: 25 September 1998 Accepted: 12 October 1998     

BQ-123, a specific endothelin (ETA) receptor antagonist,prevents ischemia-reperfusion injury in kidney transplantation

We studied the effects of the specific endothelin (ET_A) receptor antagonist, BQ-123, on reperfusion injury in a rat model of kidney transplantation. First, Sprague-Dawley rats were divided into three groups: a sham nephrectomy (SNEPH), an autotransplantation (AUTO-Tx), and an allotransplantation (ALLO-Tx) group. In a fourth group, ALLO-Tx+BQ, allografts were flushed with 20 g BQ-123 containing cold Ringer's lactate before transplantation. For the allograft groups, kidneys from white Wistar albino rats were transplanted into allogeneic Sprague Dawley recipients. Grafts were allowed 120 min of reperfusion after 40 min of cold ischemia. ET-1,2 plasma concentrations in the renal venous blood, and kidney tissue prostaglandin (PG) E₂ and leukotriene (LT) B₄ levels were studied. Diene conjugates (DC), hydroxyalkanals (HAA), hydroxyalkenals (HAE) and malondialdehyde (MDA) levels, as the products of lipid peroxidation, and protein carbonyls (PC) and protein sulphydryls (PS), as the parameters of protein oxidation, were also analyzed in the kidney tissue. Plasma ET concentrations increased significantly in the AUTO-Tx and ALLO-Tx groups (P<0.05 and P<0.01, respectively) but this increase was reversed in the ALLO-Tx+BQ group. None of the lipid peroxidation products except DCs (P<0.05) increased in the AUTO-Tx group, whereas they all increased in the ALLO-Tx group (P<0.01). Protein oxidation parameters also changed significantly (P<0.01) in the ALLO-Tx group but did not in the AUTO-Tx group (P<0.05). The differences in PGE₂ and LTB₄ levels were not significant. Histopathologic examination revealed prominent glomerular and tubular injury in the AUTO-Tx and ALLO-Tx groups but less in the ALLO-Tx+BQ group. In the last group, all parameters of lipid peroxidation (P<0.001 for all) and PCs decreased, and PSs were preserved (P<0.001 for both) when compared with the AUTO-Tx and ALLO-Tx groups. We conclude that BQ-123, in addition to inhibiting the binding of ET-1,2 to the ET_A receptor, may also inhibit the release and/or synthesis of ET-1,2 and prevent reperfusion injury in kidney transplantation.     

Protective effects of propofol against ischemia/reperfusion injury in rat kidneys

Aim: The purpose of this study was to investigate and compare the efficiency of propofol in the reduction of injury induced by free radicals in a rat model of renal ischemia/reperfusion (I/R). Method: Twenty-four Wistar rats were divided into four groups in our study. Rats in the sham group underwent laparotomy and were made to wait for 120 min without ischemia. Rats in the control group were given nothing with ischemia–reperfusion. Rats in the I/R groups were given propofol (25 mg/kg) and 10% intralipid (250 mg/kg) ip, respectively, 15 min before the ischemia for 60 min followed by reperfusion for 60 min. The kidney tissues of the rats were taken under anesthesia at the end of the reperfusion period. Evaluation of biochemical malondialdehyde (MDA), superoxide dismutase, and catalase activities and histopathological analysis were performed with these samples. Results: I/R significantly increased MDA levels (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the propofol group compared to control group (p < 0.05). In the propofol group, the level of histopathological scores is significantly decreased than control and intralipid groups in ischemia–reperfusion. Conclusion: Our results demonstrate that I/R injury was significantly reduced in the presence of propofol. The protective effects of propofol may be due to their antioxidant properties. These results may indicate that propofol anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

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.     

Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury

Abstract

Background: The present study aimed to investigate whether the inflammatory and antioxidant lycopene has a therapeutic effect against renal ischemia/reperfusion (I/R) injury. Materials and methods: In this study, 24 Wistar-Albino rats, weighing from 200 to 250?g, were divided into four groups. All rats underwent median laparotomy under anesthesia. No procedures were performed in the control group (Group C), whereas 100?mg/kg lycopene was administered by gavage in the lycopene group (Group L). The arteries of both kidneys were clamped for 45?min in the ischemia group (Group I), whereas 100?mg/kg lycopene was administered by gavage 30?min before clamping renal arteries, and ischemia was performed in the treatment group (Group T) rats. For all rats, blood samples and renal tissues were collected at 6?h of reperfusion. Samples were used to examine serum BUN, creatinine, MDA and GSH levels, and the renal tissues were used to examine MDA and GSH levels, and renal histopathologies. Results: The treatment group had statistically significant lower serum MDA levels, histopathological tubular vacuolization, loss of brush border and tubular dilatation (p?<?0.05), whereas serum BUN, creatinine, tissue MDA, and tissue and serum GSH levels were improved in favor of the treatment group, even though it was not statistically significant (p?>?0.05). Conclusion: The present study demonstrated that lycopene, which was administered prior to renal I/R injury, prevented renal damage through biochemical and histopathological parameters.     

Alpha-tocopherol and ginkgo biloba treatment protects lipid peroxidation during ischemic period in rat groin island skin flaps

Oxygen-derived free radicals have been implicated in the causation of cellular injury during low-flow ischemia and during reperfusion of previously completely ischemic tissue; they are also believed to be the causative factor in the no-reflow phenomena. Modulation of these free radical substances has been suggested as a means of decreasing the amount of tissue loss due to ischemia and subsequent reperfusion. Pretreatment of tissues with a variety of agents has been reported to minimize the production of oxygen radicals and augment tissue survival after an ischemic insult. Further evidence of free radical involvement in skin flap necrosis in a rat groin island skin flap model is presented. In addition, the effects of two different free radical scavengers, alpha tocopherol (20 mg/kg intraperitoneally once daily for a week) and ginkgo biloba (5 mg/kg orally twice a day for a week) have been investigated and compared. Since malonyldialdehyde (MDA) is the end product of lipoperoxidation which occurs in cellular membranes in an ischemic period - dependent manner, MDA levels in tissue homogenates were measured 60, 90, and 120 min after an ischemic insult. MDA levels significantly increased in a time-dependent manner during the ischemic period in the control group. Results from the determination of tissue MDA levels at biopsy sites of radical scavenger treated groups compared with the placebo group showed that the ginkgo biloba-treated rat samples had significantly lower MDA levels than control samples only at the 120 min ischemic period (p<0.01). However, protection of lipoperoxidation in alpha tocopherol-treated rat samples was detected after both the 90 and 12 min ischemic periods (p<0.01), and the magnitude of these decreased MDA levels in alpha tocopherol-treated samples was found to be greater than it was after ginkgo biloba treatment. Decreasing free radicals during reperfusion by using these agents, preferably alpha tocopherol, may be beneficial in modulating the no-reflow phenomenon and subsequent reperfusion injury, and may help to improve tissue salvage.