Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury.

BACKGROUND: The aim of this study was to investigate the possible protective effect of interleukin 18-binding protein (IL-18BP) on ischemia-reperfusion (I/R)-induced liver injury in experimental rat models. Liver is one of the most affected organs from I/R process. IL-18 is an important proinflammatory cytokine, which may induce some events such as production of reactive oxygen substances and release of various cytokines. IL-18BP acts as an inhibitor of IL-18. The relationship between IL-18 and IL-18BP has an important place in inflammatory process. MATERIALS AND METHODS: Rats were equally divided into three groups as follows: sham: Hepatic pedicle dissection was done, but hepatic pedicle clamping was not used. I/R: Sixty minutes of ischemia and 2 h of reperfusion were applied. IR + IL-18BP: Recombinant human IL-18BP (100 µg/kg) was administered 30 min before the surgery. Hepatic pedicle was clamped during 60 min of ischemia and 2 h of reperfusion was achieved. RESULTS: Liver enzyme levels were significantly lower in the IR + IL-18BP group, when compared with the I/R group. Serum and tissue levels of tumor necrosis factor-α, IL-6, and IL-18 were considerably lower in the IR + IL-18BP group, when compared with the I/R group, but hepatic interferon-γ and IL1ß levels were not significant. Serum oxidative stress index level was significantly higher in the I/R group, when compared with the IR + IL-18BP group. In immunostaining, it was observed that pathologic changes were lower in IR + IL-18BP group than the I/R group. CONCLUSIONS: IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. Additionally, these effects have been verified by histomorphologic examination and oxidative stress markers.

Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.

Monitoring Hg2+ ions in food and environmental matrices using a novel ratiometric NIR fluorescent sensor via carbonothioate-deprotection reaction.

Mercury toxicity and its environmental impact are significant concerns for public health and environmental protection. Therefore, the development of effective, rapid, and reliable detection methods for trace levels of Hg2+ is crucial. Herein, a cyanine dye bearing a carbonothioate group is reported as a potential NIR fluorescent probe for Hg2+ detection. The spectral properties of the free probe have been characterized by the presence and absence of a series of analytes. The addition of Hg2+ leads to significant changes in the fluorescence signal with distinct red coloration compared to other competing analytes, indicating that the probe is highly selective for Hg2+. The fluorescence quantum yield increases from 0.073 to 0.315. The detection limit is 0.10 µM, indicating the high sensitivity of the probe to low Hg2+ levels. The most prominent sensing features of the probe include NIR fluorescence, low cytotoxicity, ratiometric fluorescence response, and fast response compared to most of the currently available fluorescent probes. In addition, the probe can detect Hg2+ in actual samples such as foodstuff, soil, water, and live cells. Bioimaging studies have demonstrated that the present probe is highly efficient in targeting mitochondria and possesses good imaging abilities for detecting Hg2+ in cells. Therefore, these results suggest that it can be proposed as a powerful NIR fluorescent probe for the highly sensitive detection of Hg2+.

Synthesis, DFT Calculations, In Silico Studies, and Antimicrobial Evaluation of Benzimidazole-Thiadiazole Derivatives.

In this study, a series of new benzimidazole-thiadiazole hybrids were synthesized, and the synthesized compounds were screened for their antimicrobial activities against eight species of pathogenic bacteria and three fungal species. Azithromycin, voriconazole, and fluconazole were used as reference drugs in the mtt assay. Among them, compounds 5f and 5h showed potent antifungal activity against C. albicans with a MIC of 3.90 µg/mL. Further, the results of the antimicrobial assay for compounds 5a, 5b, 5f, and 5h proved to be potent against E. faecalis (ATCC 2942) on the basis of an acceptable MIC value of 3.90 µg/mL. The cytotoxic effects of compounds that are effective as a result of their antimicrobial activity on healthy mouse fibroblast cells (L929) were evaluated. According to HOMO-LUMO analysis, compound 5h (with the lower ΔE = 3.417 eV) is chemically more reactive than the other molecules, which is compatible with the highest antibacterial and antifungal activity results. A molecular docking study was performed to understand their binding modes within the sterol 14-α demethylase active site and to interpret their promising fungal inhibitory activities. Molecular dynamics (MD) simulations of the most potent compounds 5f and 5h were found to be quite stable in the active site of the 14-α demethylase (5TZ1) protein.

Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors.

In this study, two novel series of thiazolylhydrazone derivatives containing 4-ethylpiperazine (3a-3f) and 4-methoxyphenylpiperazine (3g-3l) side chains were synthesized and their structures were characterized by spectral (1H NMR, 13C NMR, and MS spectra) analyses. In vitro inhibitory activities of synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined by Ellman method. According to the results, all compounds showed a weak inhibitory effect on AChE, while promising results were obtained on BChE. Among the synthesized compounds, the activities of the derivatives carrying 4-ethylpiperazine (3a-3f) structure were found to be more effective than the compounds carrying 4-methoxyphenyl piperazine (3g-3l) derivatives. Especially, compound 3f bearing the nitro substituent was found to be the most promising compound on BChE in the series. The absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were predicted by using the SwissADME server. The potential binding mode and stability of compound 3f with BChE were investigated by the molecular docking and dynamics simulations. The results showed that 3f was strongly bound up with BChE with the optimal conformation; in addition, their binding free energy reached -167.936 ± 13.109 kJ/mol.

Investigation into the effects of static and electric fields on bone healing process: An experimental tibial fracture model study in Wistar-Albino male rats.

OBJECTIVE: In this experimental study, we aimed to investigate whether 0 Hz-Static and 50 Hz-Electric fields have an effect on bone healing. METHODS: In this study, 45 male Wistar-Albino rats were equally and randomly separated into three groups as follows: a 0 Hz-Static electric field (SEF), a 50-Hz low-frequency electric field (LFEF) and a control group. A manual fracture was performed in the left tibia diaphysis of all rats, and fractures were fixed using circular plaster over the knee. The LFEF group was exposed to 50 Hz electric field for 30 minutes a day, five days a week, for a total of eight weeks. The SEF group was exposed to 0 Hz electric field within the same time interval. The control group was held in identical environmental conditions, without exposure to electric field. Periodic radiographs were taken from all the animals. At the end of this study, rats were sacrificed and mechanical/histopathologic examinations were performed. RESULTS: Radiologic, mechanical and histologic scores of the LFEF group were lower than those of the SEF and control groups; however, no significant difference was found in group comparisons in terms of average histologic and radiologic scores (p>0.05). CONCLUSION: Results extracted from the current study suggest that 0-hz static and 50-hz electric field exposures affect bone healing tissue of tibial fracture models in rats, although it is not significant.

Research Into the Effect of Proton Pump Inhibitors on Lungs and Leukocytes.

BACKGROUND: Proton pump inhibitors (PPI) are the most commonly used medication in the world. They are prescribed as an effective treatment choice for gastrointestinal system diseases linked to hyperacidity, especially. Additionally, non-indication and unnecessary use are very common. Many publications in recent times have reported significant side effects. However, there are insufficient studies about the mechanism for these side effects. METHODS: Twenty-four Wistar albino rats were used in this study. Rats were divided into 3 groups of control, group-administered H2 receptor blockers and a group-administered PPI. Medications were administered for 30 days intraperitoneal. After 30 days, rats were euthanized and lung tissue was obtained. Lung was stained for immunohistochemical catalase, superoxide dismutase, Glutathione peroxidase, myeloperoxidase, and toluidine blue and investigated with a light microscope. Transmission electron microscopy (TEM) was used to investigate lung tissues and neutrophil leukocytes. Additionally, lung tissue had biochemical hydrogen peroxide (H2O2) levels researched. RESULTS: H2O2 amounts, produced by lysosomes with important duties for neutrophil functions in lung tissues, were found to be statistically significantly reduced in the group-administered PPI. Results from investigations of specimens obtained with immunohistochemical staining observed increases in antioxidant amounts in the PPI group. Investigation with TEM identified more inflammation findings in the lung tissue from the group-administered PPI compared to the control group and the group-administered H2 receptors. CONCLUSION: In conclusion, we identified long-term PPI use disrupts neutrophil leukocyte functions in the lung. All clinicians should be much more careful about PPI use.

Acetaminophen at different doses protects brain microsomal Ca2+-ATPase and the antioxidant redox system in rats.

Acetaminophen, an analgesic and antipyretic drug, rescues neuronal cells from mitochondrial redox impairment and reactive oxygen species (ROS). Excessive administration of acetaminophen above the recommended daily dose range has some negative effects on the brain. We investigated the effects of different doses of acetaminophen on Ca(2+)-ATPase and the antioxidant redox system in rats. Seventy rats were randomly divided into seven equal groups. The first was used for the control. One dose of 5, 10, 20, 100, 200, and 500 mg/kg acetaminophen was intraperitoneally administered to rats constituting the second, third, fourth, fifth, sixth, and seventh groups, respectively. After 24 h, brain cortical samples were taken and brain microsomal samples were obtained by ultracentrifugation. Brain and microsomal lipid peroxidation (LP) and brain calcium levels in the sixth and seventh groups were increased compared to control. LP levels in the second, third, and forth groups; brain vitamin E levels; brain and microsomal glutathione peroxidase (GSH-Px); and Ca(2+)-ATPase activity in the sixth and seventh groups were lower than in control, although brain vitamin E concentrations in the second, third, fourth, and fifth groups and microsomal GSH-Px activity in the third and fourth groups were higher than in control. Brain cortical beta-carotene and vitamin A concentrations did not differ in the seven groups. In conclusion, 5-100 mg/kg acetaminophen seems to have protective effects on oxidative stress-induced brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.

The protective effect of erdosteine on vancomycin-induced pancreatic damage in rats.

OBJECTIVE: The goal of this study was to investigate whether vancomycin (VCM) has a negative effect on pancreatic tissue and to elucidate the role of erdosteine (ERD), an expectorant and an antioxidant agent, on possible VCM-induced pancreas impairment in rats. MATERIALS AND METHODS: A total of 21 male Wistar albino rats were included in this study. All animals were equally divided into three groups as follows: Controls (n = 7), VCM treated group (200 mg/kg twice daily for 7 days intraperitoneally, n = 7) and VCM (200 mg/kg) + ERD treated group (10 mg/kg day orally ERD, n = 7). The first dose of ERD administration was performed 24 h prior to VCM injection and the study was continued for 7 days. At the end of the study, all animals were sacrificed. Blood and pancreas tissue samples were collected. For biochemical analysis, serum amylase, lipase, alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT) activities were measured. For histopathological examination, pancreas tissue samples were investigated under the light microscope. RESULTS: VCM administration has significantly increased the serum amylase, lipase, ALP, and GGT activities, when compared with the controls. VCM + ERD administration significantly decreased the serum lipase, amylase, and GGT activities. There was no statistically significant difference between the VCM + ERD treated group and only VCM treated group by means of serum ALP levels. It has been observed that there was a prominent pancreatic tissue damage in only VCM given group. However, ERD exhibited structural protection against VCM-induced pancreatic damage and this effect was statistically significant. ERD has also obtained a marked reduction in the extent of pancreatic damage. CONCLUSION: Erdosteine may play an important role in the VCM-induced pancreatic damage and may reduce the pancreatic damage both in biochemical and histopathological aspects.

Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats.

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation.

The effects of allopurinol on rat liver and spleen tissues in a chronic hyperammonemia animal model.

OBJECTIVE: To investigate whether hyperammonemia can lead to any structural change in liver and spleen tissues or biochemical changes in blood and if allopurinol (ALLO) has a protective effect in hyperammonemia. METHODS: This study was conducted between April and May 2006. Thirty-six females Wistar Albino rats were randomly divided into 3 equal groups: Controls, administered with ammonia (NH3) and administered with NH3 + ALLO groups. Ammonium acetate (2.5 mmole/kg/day) was injected to NH3 group intraperitoneally (IP) for 28 days. The other group received ammonium acetate (2.5 mmole/kg) plus ALLO (50 mg/kg) IP for 28 days. After finishing the study, blood and tissue samples were collected to perform histopathological and biochemical analysis. RESULTS: Liver and spleen tissues were normal in the control group. In NH3 group, liver tissues were minimally vacuolar and granular degenerations and moderate mononuclear cell infiltration. However, there was no histopathological change in NH3 + ALLO group. Spleen tissues were normal in NH3 group. In biochemical analysis, there was no significant difference between the groups (p>0.05). CONCLUSION: The ammonium acetate may cause minimal structural changes in rat liver and ALLO can prevent this. We found that biochemical parameters do not necessarily correlate with the histopathological findings.

Antioxidant effects of melatonin in heart tissue after induction of experimental periodontitis in rats.

The aim of this study was to evaluate the effects of melatonin on the oxidative stress in heart tissues after induction of experimental periodontitis in rats. Thirty Wistar Albino male rats were divided into four groups as follows: healthy + saline solution (Hs, n = 7), healthy + melatonin (Hm, n = 7), periodontitis + saline solution (Ps, n = 8), and periodontitis + melatonin (Pm, n = 8). Experimental periodontitis was induced using a ligature placed at the gingival margin of the maxillary second molars. Melatonin was applied intraperitoneally (10 mg/kg) every day for 2 weeks. After sacrificing the rats, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels, and melatonin levels were evaluated. The Pm group exhibited lower alveolar bone loss than the Ps group. Melatonin levels increased in the periodontitis groups, and the Pm group had lower MDA levels and higher GSH-Px levels than the Ps group. These findings suggest that melatonin administration reduces MDA and increases GSH-Px levels in heart tissue, and these effects may be due to its antioxidant properties. Further studies are needed to understand the effects of melatonin on the association between periodontitis and cardiovascular disease.

Impact of Smoking on the Ocular Surface, Tear Function, and Tear Osmolarity.

PURPOSE: This study evaluated the effects of cigarette smoking on the ocular surface, tear function, and tear osmolarity. MATERIALS AND METHODS: A total of 50 smokers with at least 5 years of heavy smoking (defined as 1 pack/day) and 51 nonsmoking, healthy individuals were enrolled. Tear osmolarity was measured with an osmometer (TearLab™ Osmolarity System). Ocular surface examinations involved corneal fluorescein staining, measurement of the tear film breakup time (TBUT), the Schirmer 1 test, measurement of corneal sensitivity with a Cochet-Bonnet esthesiometer, and conjunctival impression cytology. Dry eye symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire. The results were compared with those from an age and sex-matched control group. The Chi-squared and independent sample t-tests were used for statistical analyses. RESULTS: The smokers had significantly higher tear osmolarity values (305.38 ± 9.81 vs. 301.14 ± 7.04 mOsm/L; p = 0.014) and OSDI scores (34.13 ± 16.58 vs. 18.09 ± 9.61; p < 0.001) than the healthy controls. However, the TBUT, corneal sensitivity, and goblet cell density were significantly lower in smokers compared to healthy controls, but the fluorescein staining and Schirmer 1 test results were not statistically different between the smokers and controls. CONCLUSION: Smoking results in increased osmolarity of the tear film, which can damage the ocular surface and tear function.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat.

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine the effect of CAPE on cadmium (Cd)-induced hypertension and cardiomyopathy in rats. In particular, nitric oxide (NO) may contribute to the pathophysiology of Cd induced cardiac impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels and nitric oxide (NO, a vasodilator) levels were used as markers Cd-induced cardiac impairment and the success of CAPE treatment. Also, the findings have been supported by the histopathologic evidences. The rats were randomly divided into three experimental groups each (12), as follows: the control group, Cd-treated group (Cd) and Cd plus CAPE-treated group (Cd+CAPE). CdCl(2) in 0.9% NaCl was administrated intraperitoneally (i.p.) with a dose of 1mg/kg/day. CAPE was co-administered i.p. a dose of 10 microM/kg for 15 days. Hypertension was found to be induced by intraperitoneal administration of Cd in a dose of 1mg/kg/day on the measurements taken 15 days later. MDA levels were increased (p<0.001) in cardiac tissue and NO levels were decreased (p<0.05) in serum in the Cd group than those of the control group had. On the other hand, there was a slight difference (increase) in MDA levels in the Cd+CAPE group than the ones in the control group (p<0.003). In addition, MDA levels were decreased and NO levels were increased in the Cd+CAPE group compared with the Cd group (p<0.001, p<0.0001, respectively). As a result, treatment with CAPE significantly reversed the increased lipid peroxidation (LPO) product, MDA, and decreased NO levels in Cd treated animals. In the histopathologic examination, a significant hypertrophy in atrial and ventricular myofibrils was observed in only Cd administered group, in comparison with the control group. There was no statistically significant difference between the CAPE given and control groups by means of atrial and ventricular myofibril diameters. In conclusion, the underlying mechanism of the myocardial hypertrophy may be related to hypertension due to inhibition of NO production in the vessels, and CAPE has a protective effect on Cd-induced hypertension mediated cardiac impairment in the rats.

Effects of thymoquinone against cisplatin-induced cardiac injury in rats.

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.

Antioxidant, Antiapoptotic and Inflammatory Effects of Interleukin-18 Binding Protein on Kidney Damage Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1ß, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis. RESULTS: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups. CONCLUSIONS: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.

Effect of radioactive iodine therapy on carotid intima media thickness in patients with hyperthyroidism.

OBJECTIVE: The aim of this study was to evaluate the carotid intima media thickness (IMT) in patients with thyrotoxicosis who received radioactive iodine (RAI) treatment. METHODS: This study was planned to be conducted with two different groups of people. There were 87 patients in the patient group and 98 controls. Participants were evaluated for atherosclerosis risk factors. Mean carotid IMT was measured from three consecutive traces at the common carotid artery bifurcation. RESULTS: The mean carotid IMT was 0.81 ± 0.20 in patient group and this was higher than the controls (0.68 ± 0.19) (p < 0.01). IM thickening was positively correlated with the applied RAI dose levels in the treatment group (p = 0.029). In patients with only HT, the data of the two groups showed a significant difference, with the average IMT being higher in the patient group than that of the control group (p: 0.011). CONCLUSION: RAI used in the treatment of thyrotoxicosis increases the IMT of carotid artery independent of age and sex. This treatment yields better results with higher doses, and this effect is more marked in patients with HT. Hence, we believe that it is necessary to calculate the dose properly for hyperthyroid cases in which treatment with RAI is planned. In particular, the patients with HT need to be treated with the minimum possible dose. Further, carotid arteries should be evaluated with US following RAI treatment.

The protective effect of melatonin on remote organ liver ischemia and reperfusion injury following aortic clamping.

BACKGROUND: Severe local and systemic tissue injuries can occur after restoration of tissue oxygenation which is also known as reperfusion injury. Our objective was to investigate the possible protective effects of melatonin against IR damage in hepatic tissue following infrarenal aortic occlusion. METHODS: A total of twenty-one male Wistar-albino rats separated into three groups as follows: Group I: Laparotomy and dissection of the infrarenal abdominal aorta (AA) were concurrently performed. Group II: About 1 ml of 0.9% saline was intraperitoenally administered 30 min before and after the occlusion operation. After laparotomy and dissection, infrarenal AA was clamped for 30 minutes and then was exposed to two hours of reperfusion. Group III: The melatonin was administered 30 min before clamping of the infrarenal AA then 30 min of ischemia and two hours of reperfusion was applied. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels were remarkably higher in IR group, when compared with the sham group, and the laboratory tests returned to normal levels in IR+MEL group after treatment. Although serum IL-1ß, IL-6, IL-18, TNF-α, and IFN- γ levels have decreased in treatment group following melatonin administration, this decrement was statistically significant for serum IL-18, TNF-α, and IFN- γ parameters compared with the IR group. Serum levels of TOC and OSI were decreased and tissue levels of TAC were increased by melatonin. CONCLUSION: As a result of this study, it can be suggested that melatonin has antioxidant, anti-inflammatory and hepatoprotective effects in case of IR. KEY WORDS: Aortic occlusion, Injury, Ischemia/Reperfusion, Liver, Melatonin.

Interleukin-18 Binding Protein Pretreatment Attenuates Kidney Injury Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury following liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 24 male Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: I, Sham group, II, IR group (1-hour ischemia and 4-hour reperfusion) and III, IR + IL-18BP group (50µg/kg IL-18BP was intraperitoneally administered 30 minutes before surgery). Blood, liver and kidney samples were collected for histopathological and biochemical (hepatic and renal function, nitric oxide, malondialdehyde and glutathione levels) analysis. In addition, proinflammatory cytokines including tumor necrosis factor α, IL-1ß and IL-6 levels were measured in kidney tissues. RESULTS: IL-18BP has improved kidney functions in acute kidney damage, restored structural changes, exhibited anti-inflammatory effects by decreasing proinflammatory cytokines and regulated the oxidative stress parameters by antioxidant effect. CONCLUSIONS: Current study would be the first to evaluate the protective, antioxidant and anti-inflammatory effects of IL-18BP on renal damage induced by liver ischemia (1 hour) and reperfusion (4 hours). As a result, we have demonstrated that AKI may develop after hepatic IR with Pringle maneuver and IL-18BP pretreatment can attenuate this damage. By this way, complications related to liver IR could be minimized and also postoperative hospitalization durations, treatment costs and healing periods could be decreased.