scholarly journals Effects of Cilostazol and Diltiazem Hydrochloride on Ischemia-Reperfusion Injury in a Rat Hindlimb Model

2017 ◽  
Vol 20 (2) ◽  
pp. 058 ◽  
Author(s):  
Bekir İNAN ◽  
Selma SÖNMEZ ERGÜN ◽  
Asiye NURTEN ◽  
Canan KÜÇÜKGERGİN ◽  
Aslı ZENGİN TÜRKMEN ◽  
...  

Objective: Free radicals and neutrophils are potent sources of ischemia-reperfusion injury (I/R) and they can be limited by the use of exogenous application of some therapeutic agents. The objective of this study was to compare the effects of cilostazol and diltiazem hydrochloride in a rat hind limb model of I/R injury. Methods: Skeletal muscles submitted to 2 hours of ischemia by placing an aneurysm clip to femoral artery and reperfused after 1, 2 and 4 hours. Seventy-two Wistar-Albino rats were randomly divided into mainly four groups according to treatment agents:  Group I (control group) was treated with saline; Group II was treated with diltiazem hydrochloride; Group III was treated with cilostazol in 30% dimethyl sulphoxide; and Group IV was treated with 30% dimethyl sulphoxide intraperitoneally. These four main groups also subdivided into three subgroups according to duration of the reperfusion times.  Blood samples were taken and all rats were sacrificed. Results: Cilostazol-treated groups demonstrated a significant decrease in tissue and serum malondialdehyde (MDA) levels, and tissue myeloperoxidase (MPO ) activity compared with other groups. Increase in serum nitric oxide (NOx) level was significantly higher in all subgroups of cilastazol, diltiazem hydrochloride, and dimethyl sulphoxide groups versus the control group.Conclusion: Although these results suggest the beneficial effects of cilostazol and diltiazem hydrochloride on I/R injury, the effect of cilostazol on I/R injury seems to be more efficient than diltiazem hydrochloride.

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Fadhil G. Al-Amran ◽  
Najah R. Hadi ◽  
Haider S. H. Al-Qassam

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.


2017 ◽  
Vol 145 (3-4) ◽  
pp. 153-158 ◽  
Author(s):  
Murat Sadic ◽  
Hasan Atilgan ◽  
Arif Aydin ◽  
Gökhan Koca ◽  
Meliha Korkmaz ◽  
...  

Introduction/Objective. Medical protection of kidneys against ischemia reperfusion injury is very important. Many agents have been used for the protection of ischemia reperfusion renal tissue injury. We aimed to evaluate the radioprotective effect of lycopene on kidneys in ischemia reperfusion injury with histopathological, biochemical, and scintigraphic parameters. Methods. Twenty-one Wistar male albino rats were divided into the following three groups: lycopene, control, and sham group. In the lycopene group, lycopene was started three days before right renal ischemia reperfusion injury and continued for 15 days. In the control group, right renal ischemia reperfusion injury was applied with no medication. In the sham group, neither right renal ischemia reperfusion injury nor medication were applied. On the 15th day, all rats were sacrificed after 99mTc-dimercaptosuccinic acid (DMSA) scintigraphies were taken. Histopathological, biochemical, and scintigraphic evaluations were made. Results. The histopathological score was lower in the lycopene group. In biochemical analysis, myeloperoxidase levels were lower in the lycopene group than in the control group, but not statistically significant. Malondialdehyde and nitrite levels were lower in the lycopene group than in the control group. The postoperative mean 99mTc-DMSA uptake values were 44.82 ? 1.84 in the lycopene group, 38.92 ? 1.17 in the control group, and 50.21 ? 1.35 in the sham group. DMSA uptake values were higher in the lycopene group than in the control group. Conclusion. Lycopene seems to be an effective agent for protection of kidneys in ischemia reperfusion injury as demonstrated by the histopathological, biochemical, and scintigraphic parameters.


2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.


2021 ◽  
Author(s):  
Camila Dossi ◽  
Romina Vargas ◽  
Rodrigo Valenzuela ◽  
Luis Videla

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development...


2017 ◽  
Vol 11 (1-2) ◽  
pp. 19 ◽  
Author(s):  
Gokhun Ozmerdiven ◽  
Burhan Coskun ◽  
Onur Kaygisiz ◽  
Berna Aytac Vuruskan ◽  
Burak Asiltas ◽  
...  

Introduction: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for preventionof the ischemia reperfusion injury after testis torsion in rats.Methods: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue.Spermatogenesis was evaluated with Johnsen’s score.Results: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group inipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen’s score of the I/Rgroup was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The meanJohnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05).Conclusions: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion.


2019 ◽  
Vol 5 (2) ◽  
pp. e19-e19
Author(s):  
Leila Mohmoodnia ◽  
Sarina Safari Ahmadvand ◽  
Sahar Koushki ◽  
Behrooz Farzan ◽  
Sajad Papi ◽  
...  

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220±10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects.


2021 ◽  
Vol 6 (15) ◽  
pp. 45-51
Author(s):  
Ayşe Köse Vuruşkan ◽  
Nur ELAGÜL ◽  
Tansel SAPMAZ ◽  
Sude TOPKARAOĞLU

Aim: We aimed to investigate how bilateral renal ischemia-reperfusion (I/R) damage affects the ovaries as a distant organ and the effects of melatonin (MEL), curcumin (CUR) and melatonin+curcumin (MEL+CUR) treatments on I/R damage. Material and Method: 42 female Wistar rats were used in the study. Rats were divided into 6 groups and study was designed as follows: Control group (G1) – opening and closing the abdomen only (sham surgery group) –, I/R group (G2) – 45 min ischemia followed by 2 h reperfusion –, I/R+MEL group (G3) – 45 min ischemia, intraperitoneal (i.p) 20 mg/kg MEL injection 5 min before reperfusion, followed by 2 h reperfusion –, I/R+CUR group (G4) – 45 min ischemia, 5 min before reperfusion i.p 200 mg/kg CUR injection and then 2 hours reperfusion –, I/R+MEL+CUR group (G5) – 45 min ischemia, 5 min before reperfusion i.p 20 mg/kg MEL and 200 mg/kg CUR injection, followed by 2 hours reperfusion –. At the end of the reperfusion period, the rats were sacrificed. Right ovaries were removed from the peritoneum and fixed. After fixation and follow-up, tissue sections were stained with hematoxylin&eosin (H&E), Periodic acid-Schiff (PAS)+Hematoxylin (PAS+H) and Masson’s trichrome stains. Pathological changes were scored and statistically evaluated. Results: Compared to the control group, there was a decrease in hemorrhage, vascular congestion, follicular degeneration, inflammation, interstitial edema, vasodilation and growing follicle numbers in all groups; these changes were severe in the G2 group; Mild to moderate severity was observed in the G3, G4 and G5 groups. Conclusion: Renal I/R damage significantly affects the ovaries histopathologically. MEL, CUR, and MEL+CUR partially preserve the histological structure, but MEL treatment seems to be more effective than CUR treatment.


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jingyuan Li ◽  
Negar Motayagheni ◽  
Neusha Barakati ◽  
Mansoureh Eghbali

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.


Author(s):  
Alberto Calleri ◽  
Dorotea Roggio ◽  
Victor Navarro-Tableros ◽  
Nicola De Stefano ◽  
Chiara Pasquino ◽  
...  

AbstractHepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity.


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