Limb Ischemia-reperfusion In Rats Research Articles

Assessment of the Effects of Quercetin on Lung Injury After Hind Limb Ischemia Reperfusion in Rats

Background: Quercetin has antioxidant and anti-inflammatory effects. Although there are previous animal experi-ments investigating Quercetin’s effect on ischemia reperfusion (IR) injury in the literature, studies involving effect of lower extremity IR on remote organ are rare.Materials and Methods: 18 male Wistar Albino rats were randomly divided into 3 groups, 6 in each group as; Cont-rol (C), Ischemia-reperfusion (IR), IR-Quercetin, (IR-Q). Their weights were between 200-250 g. 30 minutes before the procedure20 mg/kgQuercetin was administered via intraperitoneal route. In the IR groups, infrarenal abdomi-nal aorta was clamped by an atraumatic microvascular clamp. After 120 minutes of ischemia and reperfusion was achieved for another 120 minutes. When reperfusion period ended, tissue samples were taken from the lungs. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activity and histopathological parameters were compared.Results: We found the MDA level in the IR group higher than the control group (p<0.0001). Lower MDA level was found in the IR-Q group compared tothe IR group (p=0.012). SOD and CAT enzyme activity in the IR group was notably lower in the control group (p<0.0001, p<0.001, respectively). Higher SOD and CAT enzyme activities were found in the IR-Q group compared to the IR group (p=0.012, p<0.001, respectively). Neutrophil infiltra-tion/aggregation, alveolar wall thickness and total lung injury score were notably higher in IR group than in C group (p=0.001, p=0.002, p<0.0001, respectively). In addition, a statistically significant decrease was observed in the Quercetin treated group in neutrophil infiltration/aggregation, alveolar wall thickness and total lung injury score compared to the IR group (p=0.023, p=0.022, p=0.002, respectively).Conclusions: We determined that intraperitoneally administered Quercetin at a dose of 20 mg/kg30 minutes before ischemia in rats reduces lipid peroxidation, oxidative stress and reduces the damage caused by IR in lung histo-pathology.Study findings suggest that Quercetin has a lung protective effect when administered before IR.

Effects of cyclosporin A pre-treatment combined with etomidate post-treatment on lung injury induced by limb ischemia-reperfusion in rats.

ObjectivesTo investigate the influence of cyclosporin A (CsA) pre-treatment and etomidate (ETO) post-treatment on lung injury induced by limb ischemia-reperfusion (I/R) in rats.MethodsRats were randomly divided into five groups: sham, I/R, I/R+CsA, I/R+ETO, and I/R+CsA+ETO. Limb I/R lung injury was established by bilateral clamping of the femoral arteries for 2 hours. Following reperfusion for 3 hours, blood gas analysis was performed. Pathological changes were assessed using immunohistochemistry. The apoptosis index (AI) and wet/dry weight ratio (W/D) were calculated. Levels of Fas protein and FasL mRNA were assessed by western blotting and RT-PCR, respectively. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected by ELISA.ResultsI/R resulted in decreased PaO2 but increased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β. Scattered punctate apoptosis and necrosis were observed by immunohistochemistry. Compared with the I/R group, the I/R+ETO and I/R+CsA groups showed increased SpO2, decreased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β, and decreased numbers of apoptotic and necrotic cells. Combined treatment with CsA+ETO resulted in more dramatic changes in these parameters.ConclusionsETO post-treatment and CsA pretreatment reduced lung injury induced by limb I/R in rats. The mechanism may be related to synergistic inhibition of Fas/FasL signaling.

Effects of FTY720 pretreatment on lung injury induced by limb ischemia-reperfusion in rats

Objective To evaluate the effects of FTY720 pretreatment on lung injury induced by limb ischemia-reperfusion (I/R) in rats. Methods Thirty healthy male Sprague-Dawley rats, weighing 230-260 g, were divided into 3 groups (n=10 each) using a random number table: sham operation group (group S), I/R group and FTY720 group (group F). Bilateral hind limb I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by 3 h of reperfusion.FTY720 was given by intragastric gavage at 3 mg·kg-1·d-1 for 7 consecutive days before I/R in group F, while the equal volume of normal saline was given instead in group I/R.At the end of reperfusion, blood samples were collected from the carotid artery for blood gas analysis, and oxygenation index (OI) was calculated.The rats were then sacrificed and lungs removed for examination of pathological changes (with light microscope) and for determination of apoptosis rate (using flow cytometry) and expression of CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, c-Jun N-terminal kinase (JNK), Bcl-2 and Bax protein in lung tissues (using Western blot). Bax/Bcl-2 ratio was calculated. Results Compared with group S, OI was significantly decreased in group I/R, and apoptosis rate was increased, the expression of CHOP, caspase-12, JNK and Bax protein was up-regulated, and the expression of Bcl-2 was down-regulated, and Bax/Bcl-2 ratio was increased in I/R and F groups (P<0.05). Compared with group I/R, OI was significantly increased, apoptosis rate was decreased, the expression of caspase-12, CHOP, Bax and JNK protein was down-regulated, and the expression of Bcl-2 was up-regulated, and Bax/Bcl-2 ratio was decreased in group F (P<0.05). The pathological changes of lungs were significantly attenuated in group F as compared with group I/R. Conclusion FTY720 pretreatment can attenuate lung injury induced by limb I/R in rats, and the mechanism may be related to inhibition of endoplasmic reticulum stress-related cell apoptosis. Key words: Extremities; Reperfusion injury; Respiratory distress syndrome, adult; FTY720

Effects of dexmedetomidine preconditioning on renal injury induced by limb ischemia-reperfusion in rats

Effects of dexmedetomidine preconditioning on renal injury induced by limb ischemia-reperfusion in rats

Effect of sevoflurane preconditioning on lung injury induced by limb ischemia-reperfusion in rats and the relationship with endoplasmic reticulum stress

Objective To investigate the effect of sevoflurane preconditioning on lung injury induced by limb ischemia-reperfusion in rats and the relationship with endoplasmic reticulum stress. Methods Forty-five healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-300 g, were randomly allocated into 3 groups(n=15 each)using a random number table: sham operation group(group S), limb ischemia-reperfusion group(group LIR), and sevoflurane preconditioning group(group SP). Limb ischemia-reperfusion was induced by clamping bilateral femoral arteries for 3 h followed by 3 h reperfusion in LIR and SP groups.In group SP, 2.5% sevoflurane was inhaled for 30 min, and 15 min later the model was established.Before ischemia and at 3 h of reperfusion(at the corresponding time point in group S), arterial blood samples were collected for blood gas analysis, and arterial oxygen partial pressure(PaO2)and arterial carbon dioxide partial pressure(PaCO2)were recorded.The rats were sacrificed at 3 h of reperfusion, and lung specimens were obtained for determination of wet to dry lung weight ratio(W/D ratio)and total lung water content(TLW)and for microscopic examination of the pathological changes, and index of quantitative evaluation for alveolar damage(IQA)was calculated.The expression of glucose-regulated protein 78(GRP78)and CCAAT/enhancer-binding protein homologous protein(CHOP)protein and mRNA in lung tissues was detected by Western blot and real-time polymerase chain reaction, respectively. Results Compared to group S, the PaO2 was significantly decreased at 3 h of reperfusion, the W/D ratio, TLW and IQA were significantly increased, the expression of GRP78 and CHOP protein and mRNA was significantly up-regulated(P 0.05). Compared to group LIR, the PaO2 was significantly increased at 3 h of reperfusion, the W/D ratio, TLW and IQA were significantly decreased, the expression of GRP78 and CHOP protein and mRNA was significantly down-regulated(P 0.05). Conclusion Sevoflurane preconditioning can ameliorate lung injury induced by limb ischemia-reperfusion in the rats, and the mechanism is related to inhibition of endoplasmic reticulum stress. Key words: Anesthetics, inhalation; Ischemic preconditioning; Extremities; Reperfusion injury; Respiratory distress syndrome, adult; Endoplasmic reticulum; Stress

Effects of postconditioning with ischema and propofol on retinal injury induced by limb ischemia-reperfusion in rats

Objective To evaluate the effects of postconditioning with ischema and propofol on retinal injury induced by limb ischemia-reperfusion (LIR) in rats.Methods Twenty-four male Wistar rats were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group S),group LIR,and propofol postconditioning + postconditioning + ischemic LIR group (group P + I + LIR).The model of LIR was established by separating and ligating the femoral artery and vein of bilateral hind limbs for 60 min followed by reperfusion.In group P + I + LIR,the animals were subjected to 4 episodes of 60 min ischemia-5 min reperfusion-5 min ischemia-5 min reperfusion and to 4 cycles of propofol 500 μg· kg-1 · min-1 infused intraperitoneally at the same time (during reperfusion)-no propofol infusion during second ischemia.At 120 min of reperfusion,blood samples were collected from the abdominal aorta for determination of serum malondialdehyde (MDA) concentrations.The eyeball was removed and the retina was cut into sections which were stained with H.E.and examined by microscopy.Results Compared with group S,the serum MDA concentration was significantly increased in group LIR,and no significant change was found in the serum MDA concentration in group P + I + LIR.The serum MDA concentration was significantly lower in group P + I + LIR than in group LIR.The structure of retina was normal in group S,oedema was found in all the layers of retina,vacuolar degeneration was observed in the most of ganglionic layers,and the structure disturbance was found in group LIR.The pathological changes of retina were significantly attenuated in group P + Ⅰ + LIR.Conclusion Postconditioning with ischema and propofol can attenuate retinal injury induced by LIR,and the mechanism is related to inhibition of lipid peroxidation in rats. Key words: Propofol ; Extremities ; Reperfusion injury ; Retina ; Ischemic postconditioning

Effects of remifentanil preconditioning on renal injury induced by limb ischemia-reperfusion in rats

Objective To evaluate the effects of remifentanil preconditioning on the renal injury induced by limb ischemia-reperfusion (I/R) in rats.Methods Twenty-seven healthy male Sprague-Dawley rats,weighing 200-250 g,were randomly assigned into 3 groups (n =9 each):sham operation group (Sham group),I/R group and remifentanil preconditioning group (RPC group).Limb ischemia was induced by clamping bilateral femoral arteries and veins for 2 h,followed by 24 h reperfusion in I/R and RPC groups.Remifentanil 1.0 μg· kg-1 · min-1 was infused via the caudal vein for 30 min before ischemia in RPC group,while the equal volume of normal saline was given in Sham and I/R groups.Blood sample was taken from the inferior vena cava at 24 h of reperfusion to measure blood urea nitrogen (BUN) and creatinine (Cr) concentrations in serum.The rats were sacrificed and the left kidney was removed for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents,cell apoptosis and microscopic examination of pathological changes.Apoptosis index was calculated.Results Apoptosis index and concentrations of BUN and Cr in serum,TNF-α and IL-6 contents,and apoptosis index were significantly higher,and the pathological changes were more severe in I/R and RPC groups than in Sham group.Compared with group I/R,concentrations of BUN and Cr in serum,TNF-α and IL-6 contents,and apoptosis index were significantly decreased,and the pathological changes were attenuated in RPC group.Conclusion Remifentanil preconditioning can attenuate renal injury induced by limb I/R in rats,and inhibition of inflammatory responses and cell apoptosis in kidney may be involved in the mechanism. Key words: Piperidines ; Reperfusion injury ; Extremities ; Kidney

Magnesium Sulfate Mitigates Lung Injury Induced by Bilateral Lower Limb Ischemia-Reperfusion in Rats

Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined. Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4). MgSO(4) mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.

Effects of ulinastatin on expression of NF-KB in lung tissues during limb ischemia-reperfusion in rats

Objective To investigate the effects of ulinastatin on the expression of NF-κB in lung tissues during limb ischemia-reperfusion(I/R) in rats.Methods Forty-eight male SD rats weighing 230-260 g were randomly divided into 3 groups (n=16 each):sham operation group (group S);I/R group; ulinastatin group (group U).A rat model of lung injury induced by I/R of hind limbs which was produced by occlusion of the bilateral femoral arteries for 2 h followed by reperfusion was established.The rats were sacrificed at 2 and 4 h of reperfusion(8 rats at each time point) and the lung tissues removed for determination of NF-κB expression (by immuno-histochemistry) and microscopic examination.W/D lung weight ratio was calculated.Results W/D lung weight ratio was significantly increased and NF-κB expression was up-regulated in group I/R compared with group S(P＜ 0.05). W/D lung weight ratio was significantly decreased and NF-κB expression was down-regulated in group U compared with group I/R (P＜0.05). The lung injury induced by I/R was reduced in group U compared with group I/R. Conclusion Ulinastatin can reduce the lung injury induced by limb I/R by down-regulating the expression of NF-κB in rat lung tissues. Key words: Trypsin inhibitors; NF kappa B; Reperfusion injury; Extremities; Lung

Heme Oxygenase-1 Mediates the Protective Effects of Ischemic Preconditioning on Mitigating Lung Injury Induced by Lower Limb Ischemia-Reperfusion in Rats

Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1). Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined. Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E(2) concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP. The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1.

Platonin Mitigates Acute Lung Injury Induced by Bilateral Lower Limb Ischemia-Reperfusion in Rats

Oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by bilateral lower limb ischemia-reperfusion (I/R). Platonin, a potent antioxidant, possesses anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury induced by lower limb I/R. Forty-eight adult male rats were allocated to receive I/R, I/R plus platonin (100 μg/kg intravenous injection immediately after reperfusion), sham instrumentation, or sham instrumentation plus platonin (denoted as the I/R, I/R-platonin, Sham, or Sham-platonin group, respectively; n = 12 in each group). Bilateral hind limb I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After sacrifice, the degree of lung injury was determined. Histologic findings revealed moderate inflammation in lung tissues of the I/R group and mild inflammation in those of the I/R-platonin group. Total cell number and protein concentration in bronchoalveolar lavage fluid as well as the leukocyte infiltration and myeloperoxidase activity in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. The pulmonary concentrations of macrophage inflammatory protein-2, interleukin-6, and prostaglandin E(2) of the I/R group were significantly higher than those of the I/R-platonin group. Moreover, the plasma nitric oxide concentration as well as the nitric oxide and malondialdehyde concentrations in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. Platonin mitigates acute lung injury induced by bilateral lower limb I/R in rats.

Saffron and its constituents: new pharmacological findings

Crocus sativus L. commonly known as saffron is a perennial stemless herb of the Iridaceae family and widely cultivated in Iran. Commercial saffron comprises the dried red stigma. Compounds considered pharmacologically active and important in saffron are volatile agents (e.g. safranal), bitter principles (e.g. picrocrocin) and dye materials (e.g. crocetin and its glycoside, crocin). In this review, new pharmacological effects of saffron and its constituents on topic such as some new clinical trials on saffron, effect on sexual activity, genoprotective effect, and prevention of cerebral, renal and skeletal muscle ischemia will be discussed. Saffron tablets (200–400mg) changed some hematological and biochemical parameters. However, these alterations were in normal ranges and they were not important clinically. Saffron (200mg) showed a positive effect on sexual function with increased number and duration of erectile events seen in patients with erectile dysfunction after taking it for ten days (P&lt;0.001). The aqueous extract of C. sativus stigmas and its constituents, crocin and safranal repressed the genotoxic potency of methyl methane sulfonate (MMS)-induced DNA damage in multiple mice organs (liver, lung, kidney and spleen), using comet assay. Saffron extract and its constituents showed some protective effects on different markers of oxidative damage in hippocampal tissue from ischemic rats and against lower limb ischemia-reperfusion in rats.

Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion

To observe the role and mechanism of CO-releasing molecule (CORM)-2 in lung injury induced by ischemia-reperfusion (IR) of hind limbs in rats. A rat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley (SD) rats were randomly divided into 5 groups (n equal to 8): sham, sham + CORM-2, IR, IR + CORM-2 and IR + dimethyl sulfoxide (DMSO). Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR+CORM-2 group and in the sham + CORM-2 group were given CORM-2 (10 micromol/kg intravenous bolus) 5 minutes before reperfusion or at the corresponding time points, while rats in the IR + DMSO group was treated with the same dose of vehicle (DMSO) at the same time. The lung tissue structure, polymorphonuclear neutrophil (PMN) count, wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) expression,IkBa degradation and nuclear factor (NF)-kB activity in the lungs were assessed. As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF-kB activity significantly increased in the IR group, but the level of IkBa decresed (P less than 0.01). Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM-1 expression significantly decreased in the IR+COMR-2 group (P less than 0.01), while the level of IkBa increased. These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-kB pathway and the leukocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.

The influence of iloprost on acute lung injury induced by hind limb ischemia-reperfusion in rats

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na +–K + ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group ( P≤0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group ( P≤0.01), but the decreases were not significant in serum MDA levels ( P=0.052). Serum TAC and lung tissue Na +–K + ATPase activity levels were found to be increased in ILO group compared to IR group ( P≤0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.

Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR + AB group received 3-AB (10 mg kg −1 intraperitoneally). The IR + DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mg kg −1) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na +/K + ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio ( p = 0.014), wet to dry weight ratio ( p = 0.000), MPO activity ( p = 0.000), and MDA levels ( p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values ( p < 0.05). Na +/K + ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.

Protective effects of a potent c5a receptor antagonist on experimental acute limb ischemia-reperfusion in rats

Objective The capacity of a potent C5a receptor antagonist to inhibit various parameters of local and remote organ injury following lower limb ischemia-reperfusion (I/R) in rats was investigated. Methods Rats were subjected to 2 h bilateral hindlimb ischemia and 4 h reperfusion. Drug-treated rats received AcF-[OPdChaWR] (1 mg/kg) iv either 10 min before ischemia or 10 min prior to reperfusion, or orally (10 mg/kg) 30 min prior to ischemia. Levels of circulating creatine kinase (CK), lactate dehydrogenase (LDH), alanine and aspartate aminotransferase (ALT/AST), creatinine, blood urea nitrogen (BUN), polymorphonuclear leukocytes (PMNs), and calcium (Ca ++) and potassium (K +) ions were determined. Other parameters measured included urinary protein levels, muscle edema, and myeloperoxidase (MPO) concentrations in the lung, liver, and muscle along with liver homogenate tumor necrosis factor-α (TNF-α) concentrations. Results Limb I/R injury was characterized by significant elevations of CK, LDH, ALT, AST, creatinine, BUN, proteinuria, PMNs, serum K +, muscle edema, organ MPO, and liver homogenate TNF-α concentrations, but a significant reduction in serum Ca 2+ concentrations. When rats were treated with AcF-[OPdChaWR], there were significant improvements in all these parameters. Conclusion These results indicate a pivotal role for C5a in inducing local and remote organ injury and suggest a possible new drug therapeutic category for preventing anticipated tissue injury associated with I/R.