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Ulcerative colitis (UC) is a chronic and inflammatory disorder of the gastrointestinal (GI) tract. UC usually worsens the daily life of the patient and may sometimes become mortal. There is no known remedy discovered against UC, yet. Rosmarinus officinalis consists of many flavonoids, phenolics, and terpenoids possessing various biological activities such as anti-inflammatory. For this reason, in the present study, anti-ulcerative colitis effect of ROME (Rosmarinus officinalis methanol extract) was investigated comprehensively by histopathological studies, a number of in vivo anti-inflammatory activities and several in vivo antioxidant activities, in addition to in vitro antioxidant activities and biochemical analyses. In addition, the toxic effects of ROME were examined. The results showed that ROME provided a significant healing effect against ulcerative colitis in rats. Both in vitro and in vivo assay results correlated with histopathological examinations. ROME exhibited minimal toxic alterations. When the results of rosemary are compared with the results of sulfasalazine, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various diseases. Although some activities of rosemary have been investigated in vitro in the previous studies, this is the first study revealing anti-ulcerative colitis effect of rosemary through histopathological studies, in vivo and in vitro assays as well as biochemical analyses overall. PRACTICAL APPLICATIONS: The results revealed and proved that ROME provided a significant healing effect against ulcerative colitis in rats. When the results of rosemary are compared with the results of sulfasalazine, a commercially available drug on the market, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various inflammatory diseases such as UC disease. In addition, ROME possesses limited toxic alterations, but not much more than the commercial drug. As a future perspective, lethal and therapeutic doses can be examined and determined. Thus, human studies can be started through this comprehensive in vivo study on rosemary which is commonly used as an edible plant and spice all over the world.

Objective The aim of this study was to compare the efficacy of multiple antioxidant (Proxeed Plus (PP) with Carnitine, Selenium, Zinc, Coenzyme Q10, Vitamin C, Folic Acid, Vitamin B12) on local random skin flap healing with the hyperbaric oxygen (HBO) therapy. Methods Fourty rats were equally divided into five groups (Control, PP, HBO, HBO + PP, PP + HBO + PP). Local random McFarlane skin flap was applied to all rats. Following the applications, evaluations were made biochemical (TAS, TOS, OSI, IL-1β, IL-6, TNF-α, TGF-β, VEGF) and histopathological parameters. Results Necrosis percentage was found to be lower in the PP + HBO + PP group than all other groups whereas the necrosis percentages of PP and HBO groups were similar. Oxidative stress rates were significantly higher in the control group compared to the other groups whereas it was lower in the PP + HBO + PP group than all other groups. The inflammation parameters were the highest in the control group and the lowest in the PP + HBO + PP group. Growth factors were higher in the PP + HBO + PP group than all other groups. Epithelialization and wound healing were better in the HBO and PP groups than in the control group. The greatest healing, epithelialization and vascularization was seen in the PP + HBO + PP group. The histopathological findings in the PP + HBO + PP group were better in each inner region than in the other groups. Conclusion Biochemical and histopathological parameters have shown that PP reduces ischemia and necrosis and increases oxygenation in flap healing by providing significant improvement thanks to the multiple molecular structures in its content.

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.

At the center of the secretory pathway, the Golgi complex ensures correct processing and sorting of cargos towards their final destination sites which are the cytoplasm, plasma membrane, and endosome-lysosome system. Recent technological developments have discovered new morphological and functional charcteristics of the Golgi apparatus. In this review, I emphasize that the Golgi apparatus is not a stable organelle instead a highly dynamic organelle changing its morphological and functional characteristics in different physiological and pathological conditions. It is not composed of a simple discontinuous parallel stacks but is composed of various domains such as cis-Golgi network, trans-Golgi network, and intercisternal network including various coated vesicles, vacuoles and tubules. Furthermore, the Golgi apparatus is not only involved in the secretory pathway, but also involved in the storage of Ca2+ very likely to smooth endoplasmic reticulum. Additionally, the Golgi apparatus might serve as a microtubule organizing center which is especially important to participate in Golgi reassembly after cell division.

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.

The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen—a seleno-organic compound with antioxidant and antiinflammatory properties—vis-a-vis CP-induced ovarian damage. Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed. Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3. Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

Introduction This study aimed to investigate the neurotoxic damage of formaldehyde (FA), which is commonly used in medicine and industrial fields, for the hippocampus of rats and the protective role of thymoquinone (TQ) against this neurotoxicity. Methods There were five groups with eight rats in each. Two control groups were formed, in one of them physiological saline was applied and in the other one corn oil was applied. FA was injected in Group 3. Group 4 was exposed to FA and TQ simultaneously. Group 5 received TQ only. At the end of the experiment animals were sacrificed and brain tissues were removed for biochemical and histopathological investigation. Results catalase (CAT), glutathione peroxidase (GSH-px) and superoxide dismutase (SOD), all known as enzymes with antioxidant activities, were increased in FA and TQ simultaneously administered group. FA caused prominent subarachnoidal hemorrhage and vacuolization. Vacuolization was not observed but occasional subarachnoidal hemorrhage was detected in the FA+TQ group. Conclusion Neurotoxic damage in hippocampus induced by FA was reverted by administration of TQ (Tab. 1, Fig. 1, Ref. 26).

The aim of this study is to show if cyclosporine has an antiallergic role in a rat model of ovalbumin-induced allergic rhinitis. The 54 rats were divided into six equal groups. The first group was a negative control group without induced allergic rhinitis; the second group a positive control with induced allergic rhinitis not receiving treatment. The remaining four groups, after induction of allergic rhinitis, received intranasal cyclosporine treatment in doses of 0.05, 0.1, or 0.2% or nasal steroid treatment. In the biochemical examination, on the surface of the tissue tumor necrosis factor (TNF) interferon (IFN), interleukin (IL)-5, IL-13, as well as IL-2, IL-4, IL-17A, and IgE were studied. Histologically, ciliary loss, increase of goblet cells, vascular congestion, and the degree of eosinophil infiltration were rated. In all treatment groups, on average, a significant reduction in all histological and biochemical values was found compared to the positive control group. Comparing each of the three cyclosporine-using groups with the group of nasal corticosteroid did not show any significant difference in the average scores. Cyclosporine nasal drops are effective to be used in an animal model of experimental allergic rhinitis without systemic effects.

Epithelial components of the organs of the digestive system are derived from the endoderm, whereas connective tissue and muscle components are derived from the mesoderm. At the 3rd-4th week of development, as a result of cephalocaudal and lateral foldings of the embryo, a portion of the endoderm-lined yolk sac cavity is incorporated in the embryo to form the primitive gut. Primitive gut is composed of four main regions: pharyngeal gut, foregut, midgut, and hindgut. The esophagus and stomach are derived from the foregut. The development of the esophagus is characterized by lengthening, widening, thickening, and histological changes. The development of the stomach is characterized by widening, thickening, and histological changes as well as positional changes. In the present study, we tried to review the morphological and functional development of the esophagus and stomach with the aid of pictures obtained from various stages of prenatal and postnatal development of the organs of rats. Previous reviews lack information on both histological and functional development of the organs.

The parenchyma of the liver and pancreas is derived from the endoderm, whereas the stroma is derived from the mesoderm. Both of them are derived from the endoderm of the foregut as the esophagus, stomach, and a part of duodenum. At the 3rd-4th of development, the liver, gallbladder and bile ducts become diverticulum hepaticum that is derived from the caudal portion of the foregut. There were inductive effects of septum transversum and cardiac mesoderm for the development of liver diverticulum. The pancreas arise from the endoderm of the foregut. The pancreas is derived from the fusion of the ventral and dorsal pancreas bulbs, which arise from the endoderm of the duodenum. The inductive effects of the notochord and dorsal aorta play a role in the development of the pancreas. In this manuscript, we attempted to review the morphological and functional development of the liver and pancreas with the aid of pictures obtained from various stages of prenatal and postnatal development in the organs of rats.

Background: Deep Brain Stimulation (DBS) is the only modality proven to be effective on selective stimulation of the deep brain structures. It was previously reported that, by using DBS, stimulation of nucleus accumbens (NA), a region that plays a pivotal role in the pathogenesis of substance addiction, is effective for the treatment of substance addiction. Objective: The purpose of the current study was to observe how the morphine-conditioned place preference changed in rats by stimulating NA with a non-invasive method, focused ultrasound (US) and to detect whether there would be any tissue damage caused by US waves. Methods: We used low-intensity focused ultrasound (LIFU), a noninvasive modality, in a place conditioning model to stimulate NA in rats. Results: At the initial stage of our study, we used morphine to induce place preference. As expected, morphine administration caused significant place preference. After the place preference was obtained by morphine, we divided the rats into two groups. One group received LIFU waves to NA and the other group received only sham, that is, no stimulation with US waves. Rats in both groups were continued to receive morphine. Then, we investigated whether LIFU and sham will reduce morphine-induced place preference or not. We observed that morphine-induced place preference had an ongoing raise in the sham group while no raise was detected in the ultrasound group. Although LIFU prevented the rats from the raise, it did not cause a significant reduction of morphine preference. Conclusion: We state that there is a need for future studies to investigate the effects of low-intensity focused ultrasound as an alternative treatment modality in addiction. Bezmiâlem Vakıf Üniversitesi Türkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tubitak )

Toluene is an organic solvent that is toxic to humans. Caffeic acid phenethyl ester (CAPE) and thymoquinone (TQ) exhibit antioxidant and antitoxic effects. We investigated the protective effects of CAPE and TQ on toluene induced hepatotoxicity. Wistar albino rats were divided into seven groups of eight. The animals were injected intraperitoneally (i.p.) with 0.1 ml/10 g/day corn oil (control I), 0.1 ml/10 g/day corn oil + 2 ml/kg/day 10% ethanol (control II), 20 mg/kg/day TQ dissolved in 0.1 ml/10 g corn oil (TQ), 10 µmol/kg/day CAPE dissolved in 10% ethanol (CAPE), 500 mg/kg/day toluene (T), toluene and TQ together (T + TQ), or toluene and CAPE together (T + CAPE). All rats were sacrificed on day 15. Liver samples were obtained for histological analysis. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate liver function. Liver sections from the control I and TQ groups exhibited normal histology. Sections from the T group exhibited sinusoid dilation, hemorrhage, vacuolization and necrosis. TQ and CAPE protected against toluene induced histopathological changes. AST and ALT levels were increased significantly in T group compared to both control groups. CAPE decreased significantly the toluene induced increase in AST and ALT levels, while TQ did not. CAPE and TQ exhibited some antitoxic and hepato-protective effects on toluene induced liver damage. © 2018, © 2018 The Biological Stain Commission.

We investigated the effects of Nigella sativa on apoptosis and gamma-aminobutyric acid (GABAA) receptor density in cerebral cortical and hippocampal neurons in a pentylenetetrazol (PTZ)-induced kindling model in rats. The PTZ kindling model was produced by injecting PTZ in subconvulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22 and 24 of the study into animals of PTZ treated (PTZ) and PTZ + N. sativa treated (PTZ + NS) groups. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the PTZ + NS group were treated also with a 10 mg/kg methanolic extract of N. sativa 2 h before each PTZ injection. Rats in the control group were treated with 4 ml/kg saline. The number of neurons that expressed GABAA receptors in the hippocampus and cerebral cortex of rats in the PTZ and PTZ + NS groups increased significantly. There was no significant difference in the number of GABAA receptors between the PTZ and PTZ + NS groups. GABAA receptor density of t...

Objective:Cadmium (CD), which is used for many industrial purposes, is a toxic agent. CD accumulates in the liver; therefore, exposure to toxic doses of Cd results in hepatic damage. Studies in rats have shown that CD induces apoptosis in hepatocytes. Curcumin is a natural compound isolated from Curcuma longa. It has a powerful anti-inflammatory affect and scavenges reactive oxygen radicals. Additionally, it has been shown to have an anti-apoptotic effect in a dose-dependent manner. The aim of the present study was to evaluate the effects of therapeutic doses of curcumin on Cd-induced hepatic apoptosis as well as hepatic biochemical and inflammatory changes in Sprague–Dawley rats.Methods:In this study, 24 female Sprague–Dawley rats (6 months old) were randomly assigned to four main groups (n=6): control, CD, CD +curcumin, and curcumin. At the end of the experiment, after collecting blood samples from the heart, the rats were sacrificed and their livers were removed for histopathological and biochemical examinations. The number of apoptotic cells, total anti-oxidant status, total oxidant status, and thiol and MPO levels were measured in liver tissue; interleukin-6 and procalcitonin levels were measured in sera.Results:Chronic CD administration induced apoptosis. The number of apoptotic cells was significantly increased in the Cd group (almost 2 fold) compared to that in the control group. However, in the CD+curcumin group, the number of apoptotic cells was significantly decreased (almost 2 fold) compared to that in the Cd group. However, there were no statistically significant differences.Conclusion:We suggest that curcumin protects the liver against toxin-induced apoptosis.

Objective:We aimed to histopathologically and biochemically investigate the protective effects of silymarin (SLY) against cardiac injury induced by a high-dose isotretinoin (ISR) administration.Methods:Thirty-two male Balb/c mice were divided into four groups: control, ISR, SLY, and co-treated (ISR+SLY) groups. For the histopathological analysis, all sections were stained with hematoxylin–eosin and Masson’s trichrome. The TUNEL detection kit was used for the detection of cardiac apoptosis. The oxidative stress markers, which included catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-red), and the glutathione S-transferase (GST) and lipid peroxidation markers, which included erythrocyte malondialdehyde (E-MDA) and plasma malondialdehyde (P-MDA), were biochemically determined. All statistical analyses were conducted with SPSS 18.0 (IBM, New York, USA) and GraphPad Prism Version 6.01 (USA). The Student’s t-test was applied to the parametric data for comprising among groups. The P-significance degree was evaluated as 95%.Results:Severe histopathological alterations were observed in cardiac tissue. The ISR group showed hemorrhage, necrosis, edema, and congestion in cardiac tissues. SLY did not improve ISR-induced histopathological changes (p>0.05). The highest number of apoptotic cells was detected in the ISR group. In the ISR+SLY group, SLY treatment reduced apoptosis (p≤0.05). Antioxidant enzyme activities (CAT, SOD, GSH-Px, GSH-Red, GSH, GST) were induced in ISR+SLY group (p=0.015, p>0.05, p=0.002, p=0.002, p=0,018, p=0.002; respectively). E-MDA (p=0.003) and P-MDA (p=0.005) levels significantly increased in the ISR group and decreased in the SLY group.Conclusion:SLY increased antioxidant enzyme activities, prevented lipid peroxidation, and decreased apoptosis. SLY was found to be an antioxidant against ISR-induced cardiac oxidative damage.

This experimental study was designed to investigate the effects of 10weeks genistein administration on oxidative stress and inflammation in serum and liver of rats fed with fructose.6-8weeks old, 40 male Sprague-Dawley rats were included. Group 1 (control) was fed with standard chow food and 100μl/kg/day/rat dimethyl sulfoxide (DMSO) administered subcutaneously; group 2 (genistein) with standard chow food and 0.25mg/kg/day/rat genistein; group 3 (fructose) with standard chow food and drinking water 20% fructose, group 4 (fructose+genistein) with standard chow food, drinking water with 20% fructose and 0.25mg/kg/day/rat genistein. TNF-α, IL-6, visfatin as inflammatory markers and 8-isoprostane as a oxidative stress marker were measured by ELISA, glucose, triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol by enzymatic colorimetric method, AST and ALT by kinetic UV method.Significantly high 8-isoprostane levels in serum (p0.001) and liver (p0.05) in group 3 compared to control group indicate that presence of oxidative stress. Significantly high TNF-α and IL-6 levels in serum (p0.05) and liver (p0.01) and visfatin levels in serum (p0.001) of group 3 indicate inflammation accompanying insulin resistance and oxidative stress. Genistein administration to fructose group causes a significant decrease in HOMA-IR (p0.001) and LDLC (p0.05) level. Significantly lower serum 8-isoprostane (p0.01) level indicates the antioxidant effect of genistein and significantly lower liver TNF-α (p0.01), serum, liver IL-6(p0.01) and serum visfatin (p0.01) levels reflect the antiinflammatory effects of genistein.Genistein administration to rats fed with fructose causes an ameliorating effect on HOMA-IR values and lipid status markers in addition to its antioxidant and antiinflammatory effects.

Hakki Oguz Kazancioglu,1 Sertac Aksakalli,2 Seref Ezirganli,1 Muhammet Birlik,2 Mukaddes Esrefoglu,3 Ahmet Hüseyin Acar1 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, Faculty of Dentistry, 3Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME) has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new application has been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE) on new bone formation in rat midpalatal suture after RME.Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performedon all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess of new bone formation.Results: New bone formation was significantly greater in CAPE group than the control group (P

The aim of this study was to investigate histological changes in hepatic tissue and effects of pentoxifylline (PTX) and caffeic acid phenethyl ester (CAPE) on these changes using histochemical and biochemical methods in rats, in which hepatitis was established by d-galactosamine (d-GAL). Rats were divided into five groups as follows: control group, d-GAL (24 h) group, d-GAL group, d-GAL + PTX group, and d-GAL + CAPE group. In histological evaluations, the control group showed normal appearance of the liver cells. However in the d-GAL groups, focal areas consisting of inflammatory, necrotic, and apoptotic cells were detected in parenchyma. Glycogen loss was observed in the hepatocytes localized at the periphery of lobule. It was found that number of mast cells of portal areas were significantly higher in d-GAL groups compared with other groups ( p = 0.0001). In addition, the number of cells with positive staining by Ki-67 and caspase-3 were significantly increased in GAL groups compared with the control group ( p = 0.0001). In biochemical analysis, there was an increase in malondialdehyde and myeloperoxidase levels, while a decrease was observed in glutathione level and glutathione peroxidase activity in groups treated with d-GAL compared with the control group. On the other hand, it was seen that, in the groups treated with d-GAL, histological and biochemical injuries in the liver were reduced by administration of PTX and CAPE. In this study, we demonstrated the ameliorative effects of PTX and CAPE on d-GAL-induced liver injury.

Aortic cross-clamping-induced ischemia–reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

OBJECTIVES We aim to evaluate the effect of ischemic preconditioning (IPreC) on testicular tissue after transient middle cerebral artery occlusion (MCAo) in Streptozotocin-induced diabetic (STZ) and non-diabetic rats. METHODS Testis injury and alterations of testosterone levels were evaluated histologically.. Testicular damage was detected by using hematoxylin- eosin and periodic acid- schiff staining and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). RESULTS Total mean serum testosterone levels decreased in all diabetic groups (p < 0.05) although remote ischemia and IPreC did not have any effect. Serious testicular tubular damage was observed in both, diabetic and ischemic groups (p 0.05). Otherwise, remote IPreC induced MNAC instead of any changes in histopathological architecture. Moreover, remote IPreC reduced the tubular degeneration against synergistic damage of both ischemia and diabetes (p < 0.05). CONCLUSIONS It can be suggested that remote ischemic preconditioning prevents testicular damage by improving histopathological alterations and inducing apoptosis, probably temporarily, after focal transient middle cerebral artery occlusion in both, diabetic and non-diabetic rats. This is the first report demonstrating protective effects of ischemic preconditioning on remote testis injury after transient middle cerebral artery occlusion in diabetic rats (Fig. 6, Ref. 23).

Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ) groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57) was higher than that of the control group (1.50±0.22) (p

Background Non-alcoholic steatohepatitis, a cause of cirrhosis, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. The aim of the present study was to investigate the effects of melatonin and quercetin on CCl4-induced steatosis characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Methods Rats were divided into 5 groups: Ethanol, Olive oil, CCl4, CCl4+Melatonin (CCl4+Mel), CCl4+Quercetin. Rats were sacrificed and livers were removed for being evaluated by histopathological, immunohistochemical and biochemical methods. Results In CCI4 group, vacuolization, vascular congestion, haemorrhage, necrosis, and inflammatory infiltration were identified. The mean tissue MDA level was increased, whereas GSH level and SOD and CAT activities were decreased in comparison with ethanol and olive oil groups. MDA levels were decreased in CCI4+Quercetin and CCI4+Mel groups versus CCI4 group. CAT activity of CCI4+Mel group was higher than that of CCI4 and CCI4+Quercetin groups. The mean tissue GSH level of CCI4+Mel group versus CCI4 group was significantly increased. Conclusions By the means of histopathological examination, we suggest that both agents are beneficial against necrotic and apoptotic cell death during steatosis. Thus, melatonin and quercetin might be beneficial in the improvement of hepatic steatosis by supporting conventional therapy in humans (Tab. 1, Fig. 5, Ref. 53).

Epithelial components of the organs of the digestive system are derived from endoderm whereas connective tissue and muscle components are derived from mesoderm. At the 3-4th of development, as a result of cephalocaudal and lateral foldings of the embryo, a portion of the endoderm-lined yolc sac cavity is incorporated in the embryo to from the primitive gut. Primitive gut is composed of four main regions which are pharyngeal gut, foregut, midgut, and hindgut; respectively. Intestines are derived from foregut, midgut and hindgut. The development of the intestines is characterised by lengthening, widening, thickening, histological and positional changes. In this manuscript we tried to review the morphological and functional development of the small and large intestines with the aid of pictures obtained from various stages of prenatal and postnatal development the intestines of rats. Previous reviews lack of information on both histological and functional development of the small and large intestines.

AIM Current stroke therapies include lipid-lowering drugs, which reduce inflammation and serve to stabilize the atherosclerotic plaque to demonstrate better outcome and neuroprotection. Peroxisome proliferator activated receptors (PPAR) ? regulates lipid homeostasis and is a target of fibrates, which have a neuroprotective function by various mechanisms. In this study, we aimed to evaluate the role of the PPAR? agonist, fenofibrate, in the modulation of cleaved caspase-3 immunoreactivity and at the final infarct volume in an experimental ischemia/reperfusion rat model by induced transient proximal middle cerebral artery occlusion. MATERIAL AND METHODS A total of 65 male Sprague Dawley rats were allocated into 4 groups; sham (n =5), experiment 1 (n=20), experiment 2 (n=20), experiment 3 (n=20). All experiment groups were divided to 3 subgroups in order to evaluate the final infarct volume at 24th hour (n=5) and the immunoreactivity of cleaved caspase -3 at different time periods [at first hour (n=5), at 6th hour (n=5), at 24th hour (n=5)] after transient middle cerebral artery occlusion (MCAo). At the study, the experiment groups (Experiment 1 and Experiment 2) were received the fenofibrate-diet during 14 days before ischemia procedure. All animals were sacrificed at 24th hours after MCAo. Infarction volumes were calculated from 2,3,5,triphenyltetrozolium chloride (TTC)- stained brain sections. RESULTS We found that fenofibrate-therapy reduced significantly more body weight than the other experiment groups (p < 0.05). At the time intervals, a decrease of immunoreactivity of cleaved caspase-3 was significantly observed with fenofibrate therapy after MCAo (p < 0.05). Chronic fenofibrate treatment before cerebral ischemia significantly reduced the infarction size after MCAo compared with the other groups (respectively; p = 0.011 and p < 0.000). CONCLUSION Fenofibrate treatment has neuroprotective effects on middle cerebral artery infarcts.

The role of oxygen radicals are known for the pathogenesis of kidney damage. The aim of the present study was to investigate the antioxidative effects of melatonin, quercetin, and resveratrol on streptozotocin (STZ)-induced diabetic nephropathy in rats. A total of 35 male Wistar rats were divided into 5 groups as follows: control, diabetes mellitus (DM), DM + melatonin, DM + quercetin, and DM + resveratrol. All the injections started on the same day of single-dose STZ injection and continued for 30 days. At the end of this period, kidneys were removed and processed for routine histological procedures. Biochemical parameters and morphological changes were examined. In DM group, blood glucose levels were significantly increased, whereas body weights were decreased compared with the control group. Significant increases in blood urea nitrogen and tissue malondialdehyde (MDA) levels and decreases in superoxide dismutase and catalase activities were detected in DM group. Administration of melatonin, quercetin, and resveratrol significantly reduced these values. Melatonin was more efficient in reducing MDA levels than other antioxidants ( p < 0.05). STZ-induced histopathological alterations including epithelial desquamation, swelling, intracytoplasmic vacuolization, brush border loss and peritubular infiltration. Additionally, basement membrane thickening and sclerotic changes were observed in glomerulus. Transforming growth factor-β1 positive cells were also increased. Melatonin, quercetin, and resveratrol significantly reduced these histopathological changes. Our results indicate that melatonin, quercetin, and resveratrol might be helpful in reducing diabetes-induced renal damage

Objective:We aimed to investigate the protective effects of curcumin (Cr) against cadmium (Cd) toxicity on the kidneys of both young and aged rats.Methods:Forty-eight young and aged female Spraque–Dawley rats were divided into control, Cd, Cr, and Cd+Cr groups. We investigated kidney damage using a histopathological scoring system and measured total antioxidant status (TAS) and total oxidant status (TOS) and interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels.Results:Kidney tissues of Cd groups showed acute histopathological alterations. Cr improved Cd-induced histopathological changes (p

Background: This study investigates the effect of microfracture as a bone marrow-stimulating(BMS) technique on rotatory cuff(RC) healing using a chronic RC tear model. Methods: Chronic retracted RC tendon tear model was created in the subscapularis(SSC) tendons of 20 New Zealand rabbits, bilaterally. The tendons were repaired after eight weeks using a single-row configuration with suture anchors. In right shoulders, tendons were repaired in a standard fashion(control group). In left shoulders, microfractures were performed on the SSC footprint before repair(microfracture group). The animals were sacrificed 8 and 16 weeks after repair. The repaired tendons were tested biomechanically for their ultimate failure load, linear stiffness and elongation at failure. Gross and histological evaluation of the tendon-to-bone healing was evaluated. Results: In every sample, the SSC tendon was attached to its footprint on the lesser tuberosity. In microfracture group, collagen fibers were organized in relatively ticker bundles at both time intervals. The mean ultimate failure load of microfracture was significantly greater than that of control group at 8 (148.4+31 N vs. 101.4+26 N; p=0.011) and 16 (155+30 N vs. 114.9+25 N; p=0.017) weeks after repair, respectively. There were no significant differences between the two groups at each time interval for linear stiffness (15.9+2.7N/mm vs. 15.8+1.3N/mm, p=0.798 and 16.9+4.3N/mm vs. 17.1+3.6N/mm, p=0.848, respectively) and elongation at failure (4.7+1.1 mm vs. 4.7+1.3 mm, p=0.848 and 4.8+1.5 mm vs. 4.9+0.9 mm, p=0.749, respectively). Conclusions: The BMS technique of microfracture on the tuberosity of the repaired chronic rotator cuff tear promotes the dynamic tendon healing with significant ultimate force to failure and apparent microscopic findings.

Neural crest cells (NCCs) derived from neuroectoderm are multipotential cells. NCCs leave the neuroepithelium and migrate to various tissues by epithelial-mesenchymal transition. In this areas NCCs differentiate to variety of cells including melanocytes, glia cells, chromaffin cells. Cancer is a complex process which involves a dinamic interaction between tumor cells and surrounding micrenvironment. Cancer cells similar to neural crest cells leave their own environments and metastasize into a different tissue. The development of the neural crest and that of cancer progression share paralel morphological and molecular characteristics. Many signalling pathway and transcription factors are mutual for both processes. To investigate neural crest developmental mechanisms will provide a better understanding for cancer development, progression and metastasis.

Purpose: We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. Methods: Twenty-four adult female Sprague–Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. Result(s): The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). Conclusion(s): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known. © 2016, Springer Science+Business Media New York.

Context: Oxidative damage due to oxidative stress is the failure of the cell’s defense against the deleterious effects of harmful agents by means of its numerous autoprotective mechanisms. Oxidative stress is a key impairment induced by various conditions, including atherosclerosis, hypertension, ischemia-reperfusion, hepatitis, pancreatitis, cancer, and neurodegenerative diseases. Evidence Acquisition: Oxidative stress is a common pathogenetic mechanism contributing to the initiation and progression of hepatic damage in cases of inflammatory liver disorders, including acute and chronic hepatitis. Antioxidant administration is a good therapeutic strategy for the treatment of hepatitis. Results: Our comprehensive review of the literature revealed that contradictory results have been obtained with many antioxidants and antioxidant agents. Conclusion: Since clinical studies to date have generally involved testing of the effects of antioxidant mixtures containing more than 2 antioxidants and also have been limited because of toxic effects of high doses of some antioxidants, antioxidant therapy for acute and chronic hepatitis needs further study.

Oxidative stress has been implicated with cardiovascular aging. Most antioxidant intervention studies have involved long-term treatments as a potential means to eliminate age-related oxidative damage in many systems. In the present study, not only light and electron microscopic pictures of the heart and thoracic aorta of young and aged and, caffeic acid phenethyl ester (CAPE) and melatonin and administered aged Sprague Dawley rats, but also antioxidant system status was evaluated. Significantly elevated levels of malondialdehyde (MDA) were observed in the heart and thoracic aorta of aged rats (P

Nervous system is highly vulnerable to the deleterious effects of age-related oxidative stress. A large body of researches has consistently confirmed the implication of free radicals both in normal cerebral ageing and ageing-related pathologies. In the present study, in addition to the light and electron microscopic pictures of brain and cerebellum of young, old and antioxidant administered old Sprague-Dawley rats, pro-oxidant status was evaluated in terms of measurements of total glutathione, lipid peroxidation (malondialdehyde) and activities of superoxide dismutase, catalase and glutathione peroxidase. Taking the results together, we suggest that supplemental administration of caffeic acid phenethyl ester and melatonin is beneficial in delaying age-related cellular damage in nervous system.

To investigate the feasibility of using porcine small intestinal submucosa (SIS) as a scaffold for repairing ovarian defects.Fourteen female New Zealand rabbits undergoing ovarian resection were randomly allocated to 2 equal groups. The unilateral ovarian defects were repaired with SIS in group 1 animals and without SIS in group 2 animals (control). The volumes of the ovaries were calculated and the severity of adhesions was assessed in 1 animal from each group each month. The ovaries were removed and examined under a microscope.The volumes of the SIS-grafted ovaries were larger than those of the operated ovaries of the control animals (P0.05). The SIS-grafted ovaries had a lower adhesion score than the operated ovaries of the control group (P0.001). SIS grafts showed hemorrhage and leukocyte infiltration until the 4th week after surgery, but the ovarian tissue appeared to be well organized from the 12th to the 16th week. At the 28th week, primordial follicles were scattered in the SIS graft.SIS graft could be used for repairing the ovary after surgery.

WOS: 000265967200008, PubMed: 18655190, Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin. (C) 2008 Wiley Periodicals, Inc. Environ Toxicol 24: 279-286, 2009.

This study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrified. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGA-treated groups and the NaCl-treated group (P

Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for 1 week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The MDA levels were increased significantly in the Pb-treated groups, but in the Pb + AdM group the MDA levels were decreased significantly when compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Pb + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity.

This study was planned to observe the effects of nitric oxide synthesis on the antioxidative defense enzymes and pancreatic tissue histology in caerulein-induced acute pancreatitis. Acute pancreatitis was induced by intraperitoneal injections of 50 microg/kg caerulein, L-arginine used for NO induction and N(omega)-nitro-L-arginine methyl ester (L-NAME) used for NO inhibition. In the caerulein group acinar cell degeneration, interstitial inflammation, oedema and haemorrhage were detected. Pancreatic damage scores were decreased with both NO induction and inhibition (p

Purpose The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and l-arginine on hepatic damage induced by caerulein-pancreatitis. Results The liver specimens of all groups showed histopathological alterations such as hepatocyte necrosis, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration. TEM studies revealed vacuole formation, mitochondrial degeneration, lysosome accumulation and necrosis. The mean histopathological score of the caerulein group was significantly different from that of each treatment group. Conclusion l-Arginine and antioxidant administration be important for reducing hepatic damage induced by AP. Improvement of hepatic damage, in turn, might be beneficial for the prognosis of AP.

Aim: The purpose of the current study was to investigate the effects melatonin on renal function. Methods: The histological appearance of the kidney and malondialdehyde, nitric oxide, glutathione and superoxide dismutase contents were determined. Serum creatinine and blood urea nitrogen levels were also assayed. Rats were divided as: Sham, pinealectomized (Px) and pinealectomized and treated with melatonin. Results: In Px group, malondialdehyde and nitric oxide levels were elevated when compared with the sham group. The Px group exhibited reduced superoxide dismutase activity and glutathione content. All of these harmful changes were restored by melatonin. Melatonin also ameliorated serum creatinine and blood urea nitrogen levels related to renal injury. The score for glomerular, tubular and interstitial changes was significantly higher in the Px group. Melatonin supplementation significantly reduced these parameters. Conclusions: This protective effect may be associated with both melatonin’s lipophilic and hydrophilic effects, thus providing on-site protection against free radical mediated damage.

In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin–eosin (H-E), periodic acid Schiff and Masson’s trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats ( p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats ( p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups ( p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels ( p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.