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Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and β-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ± 214.9, and 3722.2 ± 486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Oxygen radicals participate in the pathogenesis of heart damage. Diabetes accelerates the formation of reactive oxygen species (ROS). We investigated the effects of the antioxidants, melatonin, quercetin and resveratrol, on cardiomyopathy and apoptosis in rats with streptozotocin (STZ) induced diabetes mellitus (DM). Rats were divided into five groups of seven: control, DM, DM + melatonin, DM + quercetin and DM + resveratrol. All treatments were begun with a single dose of STZ to induce diabetes and experimental treatments were continued daily for 30 days. Morphologic and apoptotic changes were analyzed by histological assessment. The heart tissue of the control group exhibited normal histology, whereas the heart tissue of the DM group exhibited vacuolization, necrosis, congestion, infiltration and myofibril loss. The DM group exhibited significantly increased apoptosis compared to the control group. Differences in anti-apoptotic effects were statistically significant for all three antioxidant treatment groups; the anti-apoptotic effects of quercetin and resveratrol were similar. Melatonin, resveratrol and quercetin exhibited protective effects against diabetic heart damage.

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operatorinduced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L929 cells), biodegradable, and antibacterial (on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing. Scientific and Technological Research Council of Turkey [116Z501]; Inonu University Research Fund [IUBAP FDP-2018-1284] ? ACKNOWLEDGMENTS This work was supported financially by the Scientific and Technological Research Council of Turkey (Project no. 116Z501) and Inonu University Research Fund (IUBAP FDP-2018-1284) . The authors acknowledge Prof. Dr. Mehmet Fethi CEYLAN for his assistance in sternal closure surgery.

Diabetes mellitus is a complicated and serious health problem involving peripheral neuropathy. This situation causes to loss of senses, tingle and pain. Diabetic peripheral neuropathy (DPN) affects 236 million people around the World. Hence there is a need to investigate alternative ways of cure focusing on DPN. Flavonoids have potential on pain due to their permeability characteristic in the capillary microcirculation system and in lowering blood pressure. Flavonoids are common in grape seed. The main flavonoids of grape seed involve proanthocyanidins which might be an effective agent in cure of pain in DPN. The purpose of this study is to investigate effects of grape seed extract on neuropathic pain in the Streptozotocin-induced diabetic mice. In the study, 50 eight-week old BALB-C strain mice in five different groups (Control, Diabetic Control, Control+25mg/kg, Diabetes+25mg/kg and Diabetes+50mg/kg) were used. To induce diabetes in thirty of these animals, single dose Streptozotocin (180mg/kg) was administered intraperitoneally. After diabetes was observed, grape seed extract (25mg/kg and 50mg/kg body weight) was administered by oral gavage in three groups (Cont­rol+25mg/kg, Diabetes+25mg/kg and Diabetes+50mg/kg) during six weeks. At the end of the second and sixth weeks, pain threshold measurements in hot plate test were performed in line with a predetermined thermal pain model. Also the tissues of the sciatic nerve and abdominal aorta from the animals were histologically investigated. As a result hot plate measurements, pain threshold values of the animals in Diabetes+50mg/kg group significantly differed from the measurements of the animals in control group in the first measurements and from the animals in Diabetes+25mg/kg group in the second measurements (p

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Background and Aims. Sepsis causes release of free oxygen radicals that destroy membrane integrity.We evaluated the antioxidant effects of parsley, Petroselinum crispum(Pc), which has been used therapeutically for centuries in Anatolia, using a rat model of sepsis caused by cecal ligation and puncture (CLP).Methods.Wistar albino rats were separated into four groups of eight: a sham group with incised and sutured abdomen, a Pc extract(PcE) group was given 2 g/kg parsley extract for 14 days by gastric gavage, a CLP group with sepsis caused by CLP and a PcE + CLP group given parsley extract for 14 days, then made septic by CLP. PcE is given for 14 days and then sepsis is performed by the CLP procedure. Results. The groups were compared in terms of hemogram, biochemical and histological characteristics. It has been proven that the administration of PcE before CLP-induced sepsis increases neutrophil, PLT counts and TAS levels which decrease with sepsis and decreases biochemical changes (BUN, AST, ALT, LDH, TOS, OSI) which increase with sepsis, to have a protective effect on sepsis . In the PcE + CLP group, the severity of intestinal infiltration was decreased significantly compared to the CLP group; epithelial damage was similar to the CLP group. In the PcE + CLP group, the crypt and villus length was greater and the decrease in Paneth cell degranulation intensity was found to be more than for the CLP group ; also, the morphology of the cells was similar to the Sham group. Discussion. PcE exhibit potential for prophylaxis for sepsis.

Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p

Background: It was aimed to investigate effects of various conditions known to cause circadian rhythm disturbances (i.e. calorie restriction, time-restricted feeding, constant light exposure) on various peroxisomal parameters and to compare those effects with that of fenofibrate, a PPARα agonist, in rats. Methods: Plasmalogens and some fatty acids in erythrocyte lysates were analyzed by GC. Peroxisomal metabolites including very long chain fatty acids as well as phytanic and pristanic acids in plasma were measured by GC-MS. Results: Unlike calorie restricted feeding, fenofibrate treatment yielded lower level of plasma phytanic acid concentration implying higher peroxisomal α-oxidation rate. However both calorie restriction and fenofibrate treatment exhibited lower plasmalogen, DHA and arachidonic acid contents of erythrocyte lysates. Conclusion: Shared effects of conditions associated with circadian rhythm disturbances and peroxisomal induction by fenofibrate on erythrocyte membrane lipids might indicate a link between them.

Aim: Endotoxins (lipopolysaccharides, LPS) negatively affect reproduction by decreasing gonadotropin levels in the acute period. The aim of this study is to investigate the long-term effects of re-injection of endotoxin in adulthood on gonadotropin release and testicular tissue in male rats injected with endotoxin with IL-1 beta inhibitor (Q-Vd-OPh; caspase-1 inhibitor, Cİ) in the neonatal period.Material and Methods: On postnatal day 7, male rat pups were injected once with either Salin, LPS (50µg/kg), LPS (50µg/kg)+CI (1mg/kg). On postnatal 10 months, these rats were either injected with saline or LPS (50 µg/kg). 10 days after these injections, serum samples and testicular tissues were taken and the experiment was terminated.Results: Respectively, control, Salin+LPS, LPS+Salin; LPS+LPS; LPS(CI)+Salin and LPS(CI)+LPS groups were 18.8±1.6; 11.3±1.2; 23.4±2.0; 22.2±1.2 ve 23.6±1.4 ng/ml for serum LH concentrations (p0,05). Seminiferous tubule damage was observed in LPS groups (p

Objective(s): Varenicline is a selective partial agonist for the nicotinic acetylcholine receptor a4b2 subtype, which is widely used to treat smoking addiction. However, there is still no data about its potential toxic effects on tissues. In this study, we aimed to determine the varenicline-induced toxicity on reproductive and renal tissues in rats. Materials and Methods: Rats were randomly divided into two groups: control (n=10) and varenicline (n=24). Then, rats in each group were sub-divided equally as acute and chronic groups. The control rats were orally given distilled water only. Varenicline was administrated orally as follows: 1st–3rd days 9 µg/kg/day, 4th–7th days 9 µg/kg twice daily, and 8th–90th days 18 µg/kg twice daily. The rats of acute and chronic groups were sacrificed on the 45th and 90th days, respectively. Some tissue markers related to oxidative stress were measured, and sperm characteristics were observed. Results: In the acute group, varenicline led to a significant decrease in SOD activities in both kidney and testis tissues. In the chronic group, varenicline significantly increased MDA and MPO production, and reduced CAT and GPx levels in the kidneys and testes. Also, SOD and GSH levels significantly decreased in the testes. Moreover, sperm characteristics were negatively affected; histopathological deformation was observed in the testes and kidneys in all groups. Conclusion: This study showed that varenicline could detrimentally affect the kidneys and testes in both acute and chronic term usage. Further studies will provide more insights into the molecular dynamics of this damage.

We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury.

We investigated possible healing effects of melatonin (MEL) on biochemical and histological changes in the lungs of rat offspring caused by exposure to nicotine (NT) in utero. Pregnant rats were divided randomly into five groups. The SP group was treated with physiological saline. The EA group was treated with ethyl alcohol. The MEL group was treated with MEL. The NT group was treated with NT. The NT + MEL group was treated with NT and MEL. At the end of the study, the biochemistry and histopathology of lung tissue of the offspring were examined. Reduced alveolar development and increased numbers of alveolar macrophages and mast cells were observed in the NT group compared to the SP, EA and MEL groups. We also found increased malondialdehyde (MDA) levels and decreased total glutathione (GSH) levels in the NT group. Application of MEL ameliorated the histological and biochemical damage caused by NT. The number of alveoli was greater in the NT + MEL group than in the NT group. Also, the increased numbers of alveolar macrophages and mast cells resulting from exposure to NT were decreased following MEL treatment. We found that MEL caused a significant decrease in the level of MDA. Maternal exposure to NT caused significant structural and biochemical changes in the lungs of the offspring and administration of MEL ameliorated the changes.

INTRODUCTION: Different types of pelvic cancer, such as cervical, endometrial, bladder and prostate, are normally treated by radical radiotherapy, which can be used both alone or in combination with surgery and/or chemotherapy. The aim of this study is to assess the effects of concomitant Giardia intestinalis infection on acute gastrointestinal toxicity in rats that have undergone pelvic irradiation. METHODS: The study group consisted of forty female 6-month-old Wistar rats with the weight of 250 g. The rats were divided into four groups containing ten rats in each group. The study groups are as follows: Group 1 contained rats not infected with Giardia intestinalis and not irradiated, Group 2 contained rats infected with Giardia intestinalis but not irradiated, Group 3 contained rats not infected with Giardia intestinalis but irradiated, Group 4 contained rats infected with Giardia intestinalis and radiated. For the day after the end of radiation, the number of stool pellets was counted, and the operation of weighing rats was performed, and they were sacrificed the following day. The intestinal tissues were taken for histological evaluation. RESULTS: A mucosal damage, such as villus shortening, atrophy of surface epithelium, crypt loss, as well as a decrease in the number of goblet cells of the group 3 and 4, was detected as a result of the light microscopic examination. CONCLUSION: As a result of the present study, the fact that concomitant Giardia intestinalis infection aggravates acute gastrointestinal toxicity in rats that have undergone pelvic irradiation has been verified., GİRİŞ: Servikal, endometrial, mesane ve prostat gibi pelvik kanserin farklı türleri normalde ya sadece radikal radyoterapi ile yada cerrahi ve kemoterapi birlikte kombinasyon halinde tedavi edilebilir. Bu çalışmanın amacı, pelvik radyasyona maruz kalan sıçanlarda eşzamanlı Giardia intestinalis enfeksiyonunun akut gastrointestinal toksisite üzerine etkilerinin araştırılmasıdır. METOD: Çalışma grubu, 250 g ağırlığa sahip kırk adet 6 aylık dişi Wistar sıçandan oluşmaktadır. Sıçanlar, herbir grupta 10 adet sıçan olacak şekilde dört gruba ayrıldı. Çalışma grupları; Grup 1, Giardia intestinalis ile enfekte olmayan ve radyoterapi almayan sıçanlar, Grup 2, radyoterapi almamış, ancak Giardia intestinalis ile enfekte olan sıçanlar, Grup 3, Giardia intestinalis ile enfekte olmamış fakat radyoterapi almış sıçanlar, Grup 4'te hem Giardia intestinalis ile enfekte olan hemde radyoterapi alan sıçanlardan oluşmaktadır. Radyasyon bittikten sonraki gün, hayvan vücut ağırlıkları kayıtedildi ve dışkılama sıklığı hesaplandı. Ratlar perfore edilerek sakrifiye edildi, ince bağırsak dokuları histolojik inceleme için alındı. SONUÇ: Işık mikroskopik incelemesinin sonucu olarak, grup 3 ve 4 ‘te villus kısalması, yüzeyel epitelinde atrofi, kriptalarda kayıp gibi mukozal hasarlar ve goblet sayısında azalma tespit edildi. TARTIŞMA: Bu çalışmanın bir sonucu olarak, Giardia intestinalis enfeksiyonu ile eşzamanlı olarak pelvik radyoterapi uygulanması sıçanlarda akut gastrointestinal toksisiteyi arttırmıştır. zümrüt doğ

Valproic acid (VPA) is mainly prescribed to treat epilepsy. VPA has been reported to be associated with many adverse effects, including hepatotoxicity. Naringin (NRG) is a natural, therapeutically active flavanone glycoside with anti-inflammatory, anti-apoptotic, and antioxidant. The current study was therefore designed to investigate the protective effect of NRG against the VPA-induced experimental hepatotoxicity model. For this purpose, 24 Wistar albino rats were randomly divided into three groups as control (Vehicle), VPA (500 mg/kg), and NRG + VPA (100 mg/kg NRG + 500 mg/kg VPA) groups. The agents were administered via oral gavage for 14 days. Blood and liver tissue samples were taken on the end of the experiment. Biochemical analyzes were performed on the blood and liver samples. Also, malondialdehyde (MDA), superoxide dismutase (SOD) enzyme, glutathione (GSH) content, catalase (CAT) enzyme levels were examined in the liver tissue samples. Histopathological changes (hydropic degeneration and congestion) in the VPA group were increased significantly when compared to the control group (p < 0.05). We also found a decrease in enzymes of serum liver function in the VPA group. However, NRG has been shown not to prevent histopathological changes in the VPA group. According to our results with this experiment protocol, NRG could not exert sufficient protection against VPA-induced hepatotoxicity.

As aim of this study, the knowledge of whether vinpocetine (VINPO) is cardioprotective or not following isoprotenol (ISO) induced cardiac ischemia in rats. In myocard infarction, the one of the responsible mechanisms of injury is oxidative damage and inflammmation. The effect of Vinpo which is the potent antioxidant and anti inflammatory agent aimed to reveal as the biochemical, electrophysiological, and histopathologic parameters. In this study, thirty- two Wistar-Albino male rats (in the estimated weight of 250-400gm.) were divided into four groups, each consisting of eight rats. The group 1 named as sham, no any drug used in this group. Group 2 named as iso group, only isoprotenol was adminestered, the group 3 named as vinpo and iso group, here initially vinpocetine then isopretenol were used, and the group 4 named as iso and vinpo, here initially isoprotenol then vinpocetine were used. For the rats in group 2, in first and second day isoprotenol adminestered at a dose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug used. And at fifth day the experiment terminated. For the rats in group 3, at the first and second day Vinponcetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, after 30 minute isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug was used. And at fifth day experiment was terminated. Lastly for the rats in group4, first and second day isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection, at third and fourth day vinpocetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, and at fifth day experiment terminated. Prior to termination of experiment the pulse rate and ECG changes were recorded. After completion of experiment protocols blood samples and cardiac tissue samples were recieved. For the knowledge of effects of vinpocetine experimental miyocardial ischemia induced in rats, and the serum myoglobulin, total creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanin aminotransferase (ALT), measured. In myocardial tissue as an antioxidative system and an oxidative stres markers; malonylaldehate (MDA), Superoxidedismutase (SOD), Catalase (CAT), Glutathionperoxidase (GPx), GSH, Total oxidant status (TOS),Total antioxidant status(TAS),Oxidative stres index (OSI) studied. As a result, Vinpocetin showed positive impact on cardiac functions. With all of these for the best clear results, advanced studies are needed. [Med-Science 2017; 6(4.000): 629-634]

RESUMO Objetivo O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. Métodos Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. Resultados Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. Conclusões Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar. ABSTRACT Objective This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. Methods A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. Results Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. Conclusion This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Background/aim: The aim was to investigate the protective and therapeutic effects of ghrelin, which has antioxidant and antiinflammatory activity, on preventing kidney damage that occurs by induced partial ureteral obstruction in rats.Materials and methods: Twenty-eight adult male rats were included in the study, and the rats were divided into 4 groups. After the laparotomy operation on the sham group, the ureter was identified in the retroperitoneal area and was duly sutured (n = 7). Ghrelin was administered for seven days intraperitoneally, and after the nephrectomy performed on the 15th day, the rats were sacrificed (n = 7). A partial ureteral obstruction was performed after the laparotomy on the PUO group. The rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). A partial ureteral obstruction was formed after the laparotomy followed by seven days of waiting in the PUO + ghrelin group. Ghrelin was given in the dose of 10 ng/kg per day intraperitoneally for the next 7 days, and the rats were sacrificed after the nephrectomy operation performed on the 15th day (n = 7). All groups were evaluated for histological damage and catalase, superoxide dismutase, total glutathione, malondialdehyde, and myeloperoxidase levels were measured in the same tissues.Results: When the 2nd group and the sham group were compared histologically, it was observed that the damage had increased by a statistically significant level in the partial ureteral obstruction group (P = 0.001). When the group which was ghrelin-treated after the partial ureteral obstruction was compared to the group with just partial ureteral obstruction, the histopathological changes were found to decrease significantly in that group (P = 0.001). While the statistical significance of the levels of CAT, GSH, and MPO enzymes was detected among biochemical changes in the 2nd group when compared to the sham group (P < 0.01), the 3rd group showed a statistically significant difference in the levels of SOD and GSH enzymes compared to the 4th group (P < 0.05).Conclusion: Ghrelin administration to rats after the formation of an experimental partial unilateral ureteral obstruction reduces tissue damage due to ghrelin's antiinflammatory and antioxidant effects. Ghrelin administration may prevent tissue damage biochemically and histopathologically in obstructive uropathy cases.

While the pathogenesis of acetic acid (AA)-induced colitis is unclear, reactive oxygen species are considered to have a significant effect. The aim of the present study was to elucidate the therapeutic potential of dexpanthenol (Dxp) on the amelioration of colitis in rats. Group I (n=8; control group) was intrarectally administered 1 ml saline solution (0.9%); group II [n=8; AA] was administered 4% AA into the colon via the rectum as a single dose for three consecutive days; group III (n=8; AA + Dxp) was administered AA at the same dosage as group II from day 4, and a single dose of Dxp was administered intraperitoneally; and group IV (n=8; Dxp) was administered Dxp similarly to Group III. Oxidative stress and colonic damage were assessed via biochemical and histologic examination methods. AA treatment led to an increase in oxidative parameters and a decrease in antioxidant systems. Histopathological examination showed that AA treatment caused tissue injury and increased caspase-3 activity in the distal colon and triggered apoptosis. Dxp treatment caused biochemical and histopathological improvements, indicating that Dxp may have an anti-oxidant effect in colitis; therefore, Dxp may be a potential therapeutic agent for the amelioration of IBD.

The aim of this study was to investigate the possible protective effects of melatonin and β-D-glucan against AA-induced liver injury in rats. Forty (SpraqueDawley male) rats were randomly divided into 5 experimental groups: sham, acetaminophen only (AA, 900 mg/kg), melatonin (10 mg/kg) + AA (MLT), β-D-glucan (50 mg/kg) + AA (β), and melatonin + β-D-glucan + AA (MLT+β) groups. All of the rats were killed on day 11 of the experiment. Histopathological changes and biochemical parameters including levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and liver tissue malondialdehyde (MDA), activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined to assess the liver function. MDA levels were the highest in the AA group whereas activities of SOD, CAT, and GPx in the liver tissue were found as lowest in this group. MDA activities were significantly lower in the MLT+β group than in the AA group. Only GPx activities in the MLT+β group were significantly higher than those in the MLT and β groups. The serum AST and ALT levels were increased significantly following treatment with AA (p < 0.001). Pretreatment with the antioxidant compounds decreased AST levels significantly but again, the levels were still significantly higher than the sham levels (p < 0.001). There were no statistically significant differences in the microscopic damage between the S, MLT, β, and MLT+β groups (p > 0.05). This finding can be attributed to the higher efficacy of the combination of melatonin and β-D-glucan in scavenging free radicals and stimulating the antioxidant enzymes. [Med-Science 2016; 5(2.000): 539-43]

This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study.A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out.Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations.This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental.Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas.Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas.Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

Irisin is a product of fibronectin type III domain-containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis by molecular, biochemical, and morphological findings. Fourty male Wistar-Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed. Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter. Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.

Parlakpinar, Hakan/0000-0001-9497-3468; Tutun, Bugra/0000-0002-3803-0489 WOS: 000467970800001 PubMed ID: 30317873 Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress contributes to the development of diabetic complications. Dexpanthenol (Dxp) is the biological active form of pantothenic acid. We investigated whether Dxp administration could decrease oxidative stress as a way to treat renal complications of diabetes mellitus (DM). Thirty-two male Wistar albino rats were divided into four groups: control, Dxp, DM and DM + Dxp. Experimental diabetes was induced by a single dose of streptozotocin (STZ). After administration of STZ, the DM + Dxp group was administered 500 mg/kg Dxp intraperitoneally every day for 6 weeks. At the end of the study, blood glucose levels were measured and rats were sacrificed. Kidneys were embedded in paraffin, sectioned and stained with hematoxylin and eosin, and periodic acid-Schiff. The mean malondialdehyde levels, glutathione peroxidase, superoxide dismutase and catalase activities, and total antioxidant and total oxidant status also were measured. The control group was normal in histological appearance. We observed congestion, inflammation, glomerulosclerosis, tubular desquamation, loss of villi and hydropic degeneration in tubule cells in the DM group. Indicators of oxidative stress were elevated and antioxidant activity was reduced in the DM group compared to controls. In the DM + Dxp group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DM group. We found that Dxp exhibited ameliorative effects on STZ induced diabetic nephropathy by increasing antioxidant activity. Turkish Scientific and Technological Research Council (TUBITAK) under Domestic University Students Research Projects Support Programme [2209-A/2012] Our project was supported by Turkish Scientific and Technological Research Council (TUBITAK) under Domestic University Students Research Projects Support Programme, 2209-A/2012.

The aim of the present study was to investigate the protective effect of dexpanthenol (Dexp) against cisplatin (Cis)-induced hepatotoxicity. Thirty-two Sprague Dawley rats were divided into four groups: Control group (n=8), Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp), Cis group (n=8, 7 mg/kg/ip/single dose Cis) and Cis+Dexp group (n=8, 500 mg/kg/ip/daily single dose/3 days Dexp +7 mg/kg/ip/single dose Cis). MDA, CAT, GSH, GSH-Px, TOS, TAS, OSI, Total Nitrit, IL-1ß, IL-6 and TNF-? levels were analyzed in liver tissue samples. After paraffinization of liver tissue samples, histopathological (congestion, loss of glycogen, number of Kupffer cells) and immunohistochemical (caspase-3 expression) parameters were assessed on the paraffinized liver sections. GSH, TAS, TOS, OSI, Tot Nit, L-Arginine, ADMA and SDMA levels were measured in the serum samples. Statistically significant differences were found between the groups in terms of all liver tissue biochemical parameters, with the exception of IL-1ß and TNF-? levels. GSH, CAT, GSH-Px, TAS and Tot Nit levels were significantly higher in the Cis+Dexp group compared to the Cis group, whereas MDA, TOS, OSI and IL-6 levels were higher in the Cis group. Similarly, serum GSH, TAS, Tot Nit levels were higher in the Cis+Dexp group whereas TOS, L-Arginine, ADMA and SDMA levels were higher in Cis group. There were statistically significant differences between Control and Cis groups in terms of congestion increase, increase of glycogen loss, increase of Kupffer cell number and increase of caspase-3 expression (P, Firat University Scientific Research Projects Management Unit Firat University Scientific Research Projects Management Unit, University Faculty of Medicine Animal Research Ethics Committee (2016/A-36). It was funded by Inonu University Scientific Research Project Coordination Unit (Project no. 2016/179)., The present study was supported by the Inonu University Scientific Research Project Coordination Unit (grant no. 2016/179).

Background and aim It has been reported that intestinal ischemia-reperfusion (I/R) injury results from oxidative stress caused by increased reactive oxygen species. Dexpanthenol (Dxp) is an alcohol analogue with epitelization, anti-inflammatory, antioxidant, and increasing peristalsis activities. In the present study, the aim was to investigate protective and therapeutic effects of Dxp against intestinal I/R injury. Materials and methods Overall, 40 rats were assigned into five groups including one control, one alone Dxp, and three I/R groups (40-min ischemia; followed by 2-h reperfusion). In two I/R groups, Dxp (500mg/kg, i.m.) was given before or during ischemia. The histopathological findings including apoptotic changes, and also tissue and serum biochemical parameters levels, were determined. Oxidative stress and ileum damage were assessed by biochemical and histological examination. In the control (n=8) and alone Dxp (n=8; 500mg/kg, i.m. of Dxp was given at least 30min before recording), groups were incised via laparotomy, and electrical activity was recorded from their intestines. In this experiment, the effect of Dxp on the motility of the intestine was examined by analyzing electrical activity. Results In ileum, oxidant levels were found to be higher, while antioxidant levels were found to be lower in I/R groups when compared with controls. Dxp approximated high levels of oxidants than those in the control group, while it increased antioxidant values compared with I/R groups. Histopathological changes caused by intestinal I/R injury and histological improvements were observed in both groups given Dxp. In the Dxp group, electrical signal activity markedly increased compared with the control group. Conclusions Here, it was seen that Dxp had protective and therapeutic effects on intestinal I/R injury and gastrointestinal system peristaltism.

Ozyalin, Fatma/0000-0001-6486-6389; WOS: 000376813300007 PubMed ID: 27215964 The aim of the present study was to clarify the role of oxidative stress in streptozotocin induced liver injury and the possible protective effect of caffeic acid phenethyl ester (CAPE) using histological and biochemical parameters. 32 male Wistar rats were divided into 4 groups as follows: Group 1: Control animals, Group 2: Control animals given CAPE Group 3: STZ-induced diabetic animals (DM group), Group 4: STZ-induced diabetic rats given CAPE (DM+CAPE group). All the injections started on the same day of single-dose STZ injection and continued for 20 days. At the end of this period, livers were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased compared with the control group. Significant increases in tissue malondialdehyde (MDA) level and decreases in superoxide dismutase (SOD) and total glutathione (GSH) activities were detected in DM group. Administration of CAPE significantly reduced these values. STZ-induced histopathological alterations including inflammatory cell infiltration around portal triad, congestion, loss of glycogen in the hepatocytes. Additionally, degenerative cellular alterations, such as numerous vacuolizations including myelinic figure formation, pyknotic nuclei with peripheral localization of heterochromatin condensation and mitochondria! elongation were observed in cytoplasm of hepatocytes. CAPE significantly reduced these histopathological changes. Our results indicate that CAPE should be considered in the prevention of oxidative stress in diabetic liver (Tab. 3, Fig. 4, Ref. 47). Text in PDF www.elis.sk.

Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

Background and Aims Despite it being a highly potent antineoplastic drug, cisplatin has important toxic adverse effects limiting its use such as nephrotoxicity, neurotoxicity and ototoxicity. It is thought that cisplatin-induced hepatotoxicity is caused by oxidative stress resulting from increased reactive oxygen species (ROS). Apocynin (APO) exerts its antioxidant effect by reducing ROS production via inhibition of NADPH oxidase. The present study intended to demonstrate effects of cisplatin on hepatic pro-oxidant/antioxidant systems and to investigate protective effects of APO against cisplatin-induced hepatotoxicity. Methods Rats were randomly assigned into four groups (n = 8 each): a) control group; b) single dose of cisplatin (5 mg/kg); c) APO group (20 mg/kg on three consecutive days; i.p.); and d) APO plus cisplatin group. Liver tissue was assessed in all groups by biochemical and histopathological means. Also, serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase levels were studied in all groups. Results When cisplatin group was compared to controls, it was seen that lipid peroxidation product, total oxidant status and ALT levels were markedly increased, whereas superoxide dismutase and glutathione peroxidase levels were overtly decreased. APO therapy markedly prevented cisplatin-induced harmful changes in liver. Our histopathological findings such as central vein dilatation, perivenuler and periportal sinusoidal dilatation, parenchymal inflammation, vacuolar changes in hepatocytes, biliary duct proliferation and caspase-3 positive hepatocytes were in accordance with the biochemical changes. Conclusion In light of these results, it is our thought that APO has a protective role against cisplatin-induced hepatotoxicity at both biochemical and histopathological levels.

WOS: 000369611000010, PubMed ID: 26167994, This study aims to compare the effect of low-level laser therapy (LLLT) and ozone therapy on the bone healing. Thirty-six adult male Wistar albino rats were used for this study. Monocortical defects were shaped in right femur of all rats. Defects were filled with nano-hydroxyapatite graft. The animals were divided into 3 groups and each group was than divided into 2 subgroups. Then, LLLT with a diode laser was applied to the first group (G1), ozone therapy was applied to the second group (G2), and no treatment was applied to the third group as a control group (G3). Animals were sacrificed after 4th and 8th weeks and the sections were examined to evaluate the density of the inflammation, the formation of connective tissue, the osteogenic potential, and osteocalcin activity. As a result, there were no significant differences among the groups of 4 weeks in terms of new bone formation. In the immunohistochemical assessment, the number of osteocalcin-positive cells was higher in the laser group compared to the other group of 4 weeks; this difference was statistically significant in the LLLT and ozone groups (P < 0.05). Histomorphometric assessment showed that the new bone areas were higher in the LLLT and ozone groups; furthermore, there was a statistically significant difference in the LLLT in comparison with the control group at 8th week (P < 0.05). At the same time immunohistochemical assessment showed that osteocalcin-positive cells were considerably higher in G2 than G1 at 8th week (P < 0.05). The findings of this study may be the result of differences in the number of treatment sessions. Further studies are therefore needed to determine the optimal treatment modality., Scientific Research Council of Inonu University [2012-156], This project was funded by the Scientific Research Council of Inonu University (2012-156).