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    Dopamine - a Preventive Agent for Mesenteric Ischemia and Reperfusion Injury in Abdominal Compartment Syndrome
    (Wroclaw Medical Univ, 2011) Saracoglu, Ayten; Saracoglu, Kemal T.; Deniz, Mustafa; Ercan, Feriha; Yavuz, Yunus; Gogus, Yilmaz
    Objectives. Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS) and multiple organ failure. In a prospective randomized way, the effect of dopamine infusion (3 mu g/kg/min) on mesenteric perfusion, cytokine levels and intestinal histopathological changes were studied in the presence of ACS. Material and Methods. The study involved 28 male Sprague Dawley rats randomly assigned to four groups (n = 7). The external jugular vein was cannulated for infusions. In group 1, before increasing IAP, a 60-minute infusion of dopamine was performed; following this, IAP was raised and the dopamine infusion was continued for another 60 minutes. In group 2 an IAP of 20 mm Hg was maintained for 60 minutes by air insufflation. In group 3, a dopamine infusion was performed simultaneously with an IAP of 20 mm Hg for 60 minutes. Group 4 was the control. Following this phase, midline laparatomy and superior mesenteric artery (SMA) dissection was carried out in all groups and SMA perfusion was measured continuously for 30 minutes with a Doppler probe. Myeloperoxidase (MPO) activity, lipid peroxidation and glutathione (GSH) levels were measured in tissue samples and histopathological scoring was carried out. Results. The results demonstrated that SMA blood flow was increased in Group 1 and Group 3 (100.77 +/- 2.94 and 93.82 +/- 4.91 mm Hg, respectively) but decreased significantly in Group 2 (74.23 +/- 3.01 mm Hg; p < 0.01). Intestinal tissue malondialdehyde (MDA) levels (24.03 +/- 2.75 nmol/g) and MPO activity (260.5 +/- 11 u/g) were elevated in Group 2; histological scores were elevated in all groups (p < 0.05); and GSH levels were reduced in Group 2 (0.58 +/- 0.24 mu mol/g; p < 0.01). Conclusions. The results indicated that high IAP causes oxidative organ damage and that dopamine may lessen reperfusion-induced oxidative damage by reducing splanchnic perfusion and controlling the reperfusion of the intra-abdominal organs (Adv Clin Exp Med 2011, 20, 5, 613-621).
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    Dopamine - A preventive agent for mesenteric ischemia and reperfusion injury in abdominal compartment syndrome
    (2011) Saracoglu, Ayten; Saracoglu, Kemal T.; Deniz, Mustafa; Ercan, Feriha; Yavuz, Yunus; Gogus, Yilmaz
    Objectives. Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS) and multiple organ failure. In a prospective randomized way, the effect of dopamine infusion (3 ?g/kg/min) on mesenteric perfusion, cytokine levels and intestinal histopathological changes were studied in the presence of ACS. Material and Methods. The study involved 28 male Sprague Dawley rats randomly assigned to four groups (n = 7). The external jugular vein was cannulated for infusions. In group 1, before increasing IAP, a 60-minute infusion of dopamine was performed; following this, IAP was raised and the dopamine infusion was continued for another 60 minutes. In group 2 an IAP of 20 mm Hg was maintained for 60 minutes by air insufflation. In group 3, a dopamine infusion was performed simultaneously with an IAP of 20 mm Hg for 60 minutes. Group 4 was the control. Following this phase, midline laparatomy and superior mesenteric artery (SMA) dissection was carried out in all groups and SMA perfusion was measured continuously for 30 minutes with a Doppler probe. Myeloperoxidase (MPO) activity, lipid peroxidation and glutathione (GSH) levels were measured in tissue samples and histopathological scoring was carried out. Results. The results demonstrated that SMA blood flow was increased in Group 1 and Group 3 (100.77 ± 2.94 and 93.82 ± 4.91 mm Hg, respectively) but decreased significantly in Group 2 (74.23 ± 3.01 mm Hg; p < 0.01). Intestinal tissue malondialdehyde (MDA) levels (24.03 ± 2.75 nmol/g) and MPO activity (260.5 ± 11 u/g) were elevated in Group 2; histological scores were elevated in all groups (p < 0.05); and GSH levels were reduced in Group 2 (0.58 ± 0.24 ?mol/g; p < 0.01). Conclusions. The results indicated that high IAP causes oxidative organ damage and that dopamine may lessen reperfusion-induced oxidative damage by reducing splanchnic perfusion and controlling the reperfusion of the intra-abdominal organs. © Copyright by Wroclaw Medical University.
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    Experimental acute myocardial infarction in rats: HIF-1?, caspase-3, erythropoietin and erythropoietin receptor expression and the cardioprotective effects of two different erythropoietin doses
    (Elsevier Gmbh, Urban & Fischer Verlag, 2013) Bagla, Aysel Guven; Ercan, Ertugrul; Asgun, Halil Fatih; Ickin, Meltem; Ercan, Feriha; Yavuz, Ozlem; Bagla, Suat
    The cardioprotective effects of two different doses of erythropoietin administration were analyzed in rats with experimental myocardial infarction. None, saline, standard-dose (5000 U kg(-1)) and high-dose (10,000 U kg(-1)) of human recombinant erythropoietin alpha were administered intraperitoneally in Wistar rats with myocardial infarction induced by coronary artery ligation. Infarct sizes measured after triphenyltetrazolium chloride staining, levels of biochemical markers, histopathology examined by light and electron microscopy, and immunohistochemical expressions of erythropoietin, erythropoietin receptor, hypoxia inducible factor-1 alpha and caspase-3, were analyzed. Lower scores of infarction and hemorrhage, lower number of macrophages and higher score of vascularization surrounding the infarct area were observed in the erythropoietin administered groups (p < 0.05). Erythropoietin administration after myocardial infarction reduced the area of infarction and hemorrhage. There were hypoxia inducible factor-1 alpha and caspase-3 expressions in the marginal area, and erythropoietin and erythropoietin receptor expression in both marginal and normal areas (p < 0.001). Vascularization, erythropoietin expression in the normal area and vascular erythropoietin expression were positively correlated with human erythropoietin levels. The cardioprotective effects of erythropoietin treatment were independent of endogenous erythropoietin/erythropoietin receptor activity. Moreover exogenous erythropoietin treatment did not suppress endogenous erythropoietin. Erythropoietin administration after myocardial infarction reduced caspase 3 expression (apoptotic activity) and induced neovascularization around the infarct area. Higher erythropoietin administration did not provide an additional benefit over the standard-dose in myocardial protection. (C) 2013 Elsevier GmbH. All rights reserved.
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    Garlic Extract Ameliorates Renal and Cardiopulmonary Injury in the Rats with Chronic Renal Failure
    (Taylor & Francis Ltd, 2011) Deniz, Mustafa; Sener, Goksel; Ercan, Feriha; Yegen, Berrak C.
    Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective and antioxidant effects of aqueous garlic extract (AGE) in a rat model of CRF. Male Sprague-Dawley rats were randomly assigned as either CRF group with 5/6 reduction in the renal mass or sham-operated control group. CRF group received either saline or AGE (250 mg/kg/day/1 mL) orally for 3 weeks. At the end of the 3 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity, and TNF-alpha alpha and IL-1 beta beta levels were measured in the serum samples, while malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity were determined in the kidney, lung, and heart samples. CRF caused significant decreases in tissue GSH, which were accompanied with significant increases in MDA levels and MPO activities, while the circulating levels of the LDH activity, creatinine, BUN, TNF-alpha alpha, and IL-1 beta beta were elevated. AGE treatment alleviated CRF-induced oxidative changes in the injured tissues, while CRF-induced elevations in the blood levels of the pro-inflammatory cytokines and LDH were reduced. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues and that the protective effects of garlic on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and pro-inflammatory mediators. These findings suggest that garlic, as a supplementary to diet, may have a potential therapeutic use in delimitating the systemic oxidant effects of CRF on remote organs.
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    Prophylactic feeding with immune-enhanced diet ameliorates chemoradiation-induced gastrointestinal injury in rats
    (Taylor & Francis Ltd, 2010) Atasoy, Beste M.; Deniz, Mustafa; Dane, Faysal; Ozen, Zeynep; Turan, Pinar; Ercan, Feriha; Cerikcioglu, Nilguen
    Materials and methods: Forty-eight Sprague-Dawley rats were divided into control (C, n = 6), irradiation (IR, n = 14), fluoropyrimidine (5-FU, n = 14)-treated, IR + 5-FU (n = 14)-treated groups. Half of each irradiated and/or 5-FU-treated groups were previously fed with IED containing arginine, omega-3-fatty acids and RNA fragments, while the other half were fed a standard rat diet (SD) for eight days before the induction of IR or injection of 5-FU. In IR groups, whole abdominal irradiation (11 Gy) was performed with 6 MV photons. In the 5-FU groups, fluoropyrimidine (100 mg/kg) was administered intraperitoneally 30 min prior to irradiation. All animals were sacrificed on the 4th day of IR or 5-FU injection. Results: Bacterial colony counts in the ceca and mesenteric lymph nodes of IED-fed rats, which have received either 5-FU and/or irradiation were significantly lower than the corresponding SD-fed groups. Morphometric results revealed that gastric, ileal and colonic injuries were less in IED-treated IR or IR + 5-FU + IED groups, as compared to SD-fed groups. However, IED did not alter DNA fragmentation ratios. Conclusion: Prophylactic feeding of IED has a protective effect on chemoradiation-induced gastrointestinal injury, which appears to involve the eradication of bacterial overgrowth.
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    Protective Effect of Erythropoietin on post-MI Liver Tissue
    (2022) Gülen, Meltem İçkin; Bağla, Aysel Güven; Kaya, Özlem Tuğçe Çilingir; Ercan, Feriha
    Aim: Cardiac hepatopathy arises due to heart failure and influences has effects on heart recovery after myocardial infarction (MI).The aim of this study was to investigate the protective effect of Erythropoietin (EPO) on liver tissue exposed to ischemia due to MI.\rMaterial and Methods: Experimental MI was established by left anterior descending coronary artery ligation (CAL) and EPO or saline was injected immediately after CAL to five groups of rats, which groups are Control, Saline, EPO 5000, EPO 10000, CAL+1h. CAL+1h group was sacrificed one hour after CAL without any treatment. Other groups were sacrificed six hours after the operation. Liver tissues were examined histopathologically by Hematoxylin Eosin (HE) staining and electron microscopy. \rResults: Degenerative changes in liver tissue such as vacuolization, sinusoidal dilatation, hepatocyte pyknosis, Kuppfer cell activation were observed. Vacuolization, and sinusoidal dilatation increased in the Saline group compared to the control group (p=0.010 for both). Degenerated hepatocytes with pyknotic nuclei as well as activated Kuppfer cells were decreased in the EPO 10000 group compared to the Saline group (p=0.009), and activated Kupfer cells were decreased compared to the Saline and CAL+1h groups (p=0.035 and p=0.019, respectively).\rConclusion: EPO protected liver tissue from histopathological damages regardless of dose, when given at the time of MI. EPO, when given immediately after MI, protected liver tissue from histopathological damage regardless of dose. Considering the mutual interaction of liver and heart,applying EPO to MI patients at first sight may prevent post-MI liver damage and contribute to the recovery of the heart.
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    Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats
    (Cambridge Univ Press, 2013) Duman, Deniz Guney; Kumral, Zarife Nigar Ozdemir; Ercan, Feriha; Deniz, Mustafa; Can, Guray; Yegen, Berrak Caglayan
    Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTX-induced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.