Bulent Uysal | Gulhane Military Medical Academy (original) (raw)

Papers by Bulent Uysal

It is well known that the intake of paraquat (PQ) causes severe tissue injury leading to numerous... more It is well known that the intake of paraquat (PQ) causes severe tissue injury leading to numerous fatalities. Considering that the main target for PQ toxicity is the lung and involves the production of reactive oxygen and nitrogen species, tran- scription factors and inflammatory cytokines, it may be hypothesized that the combination of a potent antiinflammatory and antioxidant agent may

Experimental Biology and Medicine

Various studies have been performed to find out novel treatment strategies for acute necrotizing ... more Various studies have been performed to find out novel treatment strategies for acute necrotizing pancreatitis (ANP). Inhibition of poly(ADP-ribose) polymerase (PARP) is shown to reduce inflammation in several pathological conditions. We aimed to evaluate the efficacy of benzamide, a PARP inhibitor, in an experimental model of ANP. Thirty Sprague-Dawley rats were divided into three groups: sham-operated, ANP and ANP + benzamide groups. All groups except the sham-operated group were subjected to the ANP procedure, induced by infusing of 1 mL/kg of 3% sodium taurocholate into the common biliopancreatic duct. The ANP + benzamide group received 100 mg/kg/day benzamide intraperitoneally for a total of three days after induction of pancreatitis. The surviving animals were killed at the fourth day and the pancreas was harvested for biochemical, microbiological and histological analysis. Blood samples were also obtained from the animals. In the ANP group, a significant increase was observed ...

Paracetamol (acetaminophen; APAP), a commonly-used analgesic and anti-pyretic drug, is usually sa... more Paracetamol (acetaminophen; APAP), a commonly-used analgesic and anti-pyretic drug, is usually safe when administered at therapeutic doses in children. However, at overdoses, APAP has the potential for causing fulminant hepatic necrosis and nephrotoxicity in both humans and animals [1]. In pre-school children, many poisonings are due to chemical or pharmaceutical preparations like APAP which is an important example for poisoning with pharmaceutics [2]. Liver has an important role in the metabolism of toxic chemicals, certain drugs and environmental pollutants [3]. Using the cytochrome P450 pathway, APAP is converted to a highly toxic metabolite, namely N–acetyl–p–benzoquinamine (NAPQI) [4]. By this way, overdose of APAP leads to accumulation of NAPQI, mitochondrial dysfunction and leads to acute hepatic necrosis [4]. In the present issue of the Journal of Experimental and Integrative Medicine, we read with great interest the published article by Anbarasu et al [5] reporting a protec...

/ Thematic Poster Session / Sunday, May 15/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), A52 SM... more / Thematic Poster Session / Sunday, May 15/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), A52 SMOKING AND LUNG DISEASE ... Evaluation Of In-Utero Smoke Exposure To Fetus ... , O. Onguru , B. Uysal , E. Oztas , M. Kul , A. Guven , SU Sarici T. Tunc1 1 1 1 2 1 1

Objective: Reactive oxygen species are known to increase on a chronic wound background. We theref... more Objective: Reactive oxygen species are known to increase on a chronic wound background. We therefore investigated the possible efficacy of the topical administration of melatonin and vitamin E, known to have radical scavenging properties, in the ischemic wound model.

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology, Jan 20, 2014

The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) ... more The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural i...

Human & Experimental Toxicology, 2014

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoni... more Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p ¼ 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Interdisciplinary Toxicology, 2008

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as must... more Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects.

Annales de Chirurgie Vasculaire, 2010

Renal Failure, 2014

Objectives: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive product... more Objectives: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury. Methods: Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW + 3-AB groups. All groups except control group were subjected to ESW procedure. ESW + 3-AB group received 20 mg/kg/day 3-aminobenzamide intraperitoneally at 2 h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained. Results: Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p50.05, ESW vs. ESW + 3-AB). Histopathological injury score were significantly lower in treatment group than the ESW group (p50.05, ESW vs. ESW + 3-AB). Conclusion: Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.

Annals of vascular surgery, 2011

Severe neurological injury still represents one of the most devastating complications occurring a... more Severe neurological injury still represents one of the most devastating complications occurring after surgical repair of thoracoabdominal aneurysms. We aimed to investigate the role of rosuvastatin (RSV) against ischemia/reperfusion injury in an experimental model of spinal cord ischemia in rats. Experimental groups included control group (n = 8), ischemia/reperfusion group (n = 8) undergoing aortic occlusion without pharmacologic treatment, and RSV-treated group (n = 8) receiving 10 mg/kg/day of RSV orally for 3 days before spinal cord ischemia. Spinal cord ischemia was induced by occlusion of the abdominal aorta between the left renal artery and aortic bifurcation for 45 minutes, followed by reperfusion. Neurological status was assessed before spinal ischemia and at 48 hours postoperatively. Spinal cords were harvested for histopathologic examination with hematoxylin-eosin staining and biochemical analysis for tissue malondialdehyde, superoxide dismutase, and glutathione peroxidas...

World Journal of Surgery, 2009

Background Intestinal ischemia/reperfusion (IR) induces a systemic inflammatory response and rele... more Background Intestinal ischemia/reperfusion (IR) induces a systemic inflammatory response and releases harmful substances that may affect the function and integrity of distant organs such as lung, liver, and kidney. We conducted this study to find out if proanthocyanidins (PA) has protective effects against mesenteric IR injury and mesenteric IR-induced intestinal and distant organ injury. Materials and methods Thirty-two Sprague-Dawley rats were divided into four groups: control, control ? PA, IR, IR ? PA. The IR and IR ? PA groups were subjected to mesenteric arterial ischemia for 60 min and reperfusion for 6 h. The Control ? PA and IR ? PA groups were administered PA (100 mg/kg/day via oral gavage) for 7 days prior to injury insult. We collected ileal and distant organ tissues, such as pulmonary, hepatic, and kidney specimens to measure tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitrite plus nitrate (NO x ), and we then evaluated histological changes.

Scandinavian Journal of Clinical & Laboratory Investigation, 2011

Objective. Previously, it was shown that ozone and S-methylthiourea (SMT) treatments had ameliora... more Objective. Previously, it was shown that ozone and S-methylthiourea (SMT) treatments had ameliorative effects on experimental models of acute necrotizing pancreatitis (ANP). It is possible that the combination of ozone and SMT may be more effective than either therapy. Therefore, we investigated the effi cacy of combination therapy with ozone and SMT in an experimental rat model of ANP. Material and methods. Sprague-Dawley rats were divided into fi ve experimental groups. Groups were designed as Sham-operated, ANP, ANP ϩ Ozone, ANP ϩ SMT and ANP ϩ Ozone ϩ SMT. A model of ANP was induced by injection of sodium taurocholate into the common biliopancreatic duct. Four days after induction, blood and tissue samples were obtained for biochemical, microbiological and histopathological analysis. Results. Survival rates, serum amylase, lipase and neopterin levels, tissue oxidative stress parameters, bacterial translocation and tissue injury scores were better in the ozone and SMT groups than in the ANP group. There was no bacterial translocation in the ozone-treated groups. Tissue injury scores in the ozone group were better compared to all ANP induced groups. Ozone and SMT treatment in combination did not have better biochemical, microbiological and histological data compared to ozone or SMT treatments separately in experimental ANP. Conclusions. The combination of ozone and SMT did not provide any therapeutic advantage in ANP possibly because SMT inhibited nitric oxide synthesis which was needed for ozone action.

Renal Failure, 2012

Introduction: This study was designed to investigate the possible beneficial effects of medical o... more Introduction: This study was designed to investigate the possible beneficial effects of medical ozone therapy (OT), known as an immunomodulator and antioxidant, on the renal function, morphology, and biochemical parameters of oxidative stress in kidneys subjected to ischemia/reperfusion injury (IRI). Materials and methods: Thirty male Sprague-Dawley rats were classified into three groups: control, renal IRI, and renal IRI þ OT. The IRI group was induced by bilateral renal ischemia for 60 min, followed by reperfusion for 6 h. After reperfusion, the kidneys and blood of rats were obtained for histopathologic and biochemical evaluation. Results: Renal IRI increased the tissue oxidative stress parameters (lipid peroxidation, protein oxidation, and nitrite plus nitrate) and decreased the antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase). The serum neopterin levels showed correlation with oxidative stress parameters. All these parameters were brought to control values in the treatment group. Histopathologically, the kidney injury in the treatment group was significantly lesser than in the renal IRI group. Conclusions: Our results clearly showed that OT has beneficial effect to protect kidney against IRI. The serum neopterin levels might be used as a marker to detect the degree of renal IRI.

Renal Failure, 2008

Introduction. Nitric oxide (NO) and peroxynitrite (OONO -) are implicated in the pathophysiology ... more Introduction. Nitric oxide (NO) and peroxynitrite (OONO -) are implicated in the pathophysiology of renal ischemia/reperfusion (I/R). The aim of this study was to investigate and compare the efficiency of S-methylisothiourea (SMT), an iNOS inhibitor, and mercaptoethylguanidine (MEG), a scavenger of peroxynitrite, on renal dysfunction and injury induced by I/R of rat kidney. Materials and Methods. Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, I/R, I/R+SMT, and I/R+MEG. Rats were given SMT (10 mg/kg ip) or MEG (10 mg/kg ip) 6 h prior to I/R and at the beginning of reperfusion. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO x ) were determined in the renal tissue. Serum creatinine (S Cr ), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. SMT and MEG significantly reduced the I/R-induced increases in S Cr , BUN, and AST. Both SMT and MEG attenuated the tissue NO x levels, indicating reduced NO production. In addition, SMT and MEG markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Interestingly, MEG exerted a greater renoprotective effect than SMT. Conclusions. These data support the finding that iNOS and peroxynitrite are involved in the renal I/R injury, and suggest that a scavenger of peroxynitrite might be more effective than iNOS inhibitors as a therapeutic intervention.

Pediatric Surgery International, 2014

Purpose Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an unco... more Purpose Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. Methods Newborn pups were randomized into three groups immediately after birth (Control, NEC ? Placebo and NEC ? Etanercept). Pups in the NEC ? Placebo and NEC ? Etanercept groups were subjected to an NECinducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC ? Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. Results The histopathological injury score of rats in the NEC ? Placebo group was significantly higher compared to the NEC ? Etanercept and Control groups (p \ 0.05 for both comparisons). Tissue levels of tumor necrosis factora, interleukin-1b, and malondialdehyde were higher in the placebo group compared to the Etanercept group. Conclusion Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-a and interleukin-1b.

Pancreas, 2010

Objectives: Our aims were to evaluate the efficacy of ozone therapy (OT) in an experimental rat m... more Objectives: Our aims were to evaluate the efficacy of ozone therapy (OT) in an experimental rat model of acute necrotizing pancreatitis (ANP) and to compare its effects with hyperbaric oxygen (HBO) therapy in this entity.

Neurochemical Research, 2008

Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. Due to ... more Hyperbaric oxygen (HBO) is known to cause oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. The present study was performed to elucidate the relation of HBO exposure time to its oxidative effects in rats' brain cortex tissue. For this purpose, 49 rats were randomly divided into five groups. Except the control group, study groups were subjected to three atmospheres HBO for 30, 60, 90, and 120 min. Their cerebral cortex layer was taken immediately after exposure and used for analysis. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and nitrate-nitrite (NO X ) levels were determined. TBARS and SOD levels were found to increase in a time-dependent manner. GSH-Px activity reflected an inconsistent course. NO X levels were found to be increased only in the 120 min exposed group. The results of this study suggests that HBO induced oxidative effects are strongly related with exposure time.