Search

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.

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.

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.

Lipopolysaccharide (LPS)-induced endotoxemia can cause serious organ damage such as acute lung injury and death by triggering the secretion of proinflammatory cytokines and acute-phase reactants. The goal of this study was to evaluate the effects of β-glucan on inflammatory mediator levels and histopathological changes in LPS-induced endotoxemia.Forty-seven male Wistar albino rats were randomly allocated into four groups as follows: control group, LPS group (10 mg/kg LPS), LPS + β-glucan group (100 mg/kg β-glucan before LPS administration), and β-glucan group. Twelve hours after LPS administration, lung and serum samples were collected. Concentrations of IL-6, IL-8, C-reactive protein (CRP), and procalcitonin were measured in the serum at hours 0 (basal) and 12. The severity of lung damage was assessed by an appropriate histopathological scoring system.Serum levels of CRP in the LPS group at 12 h were significantly higher than in the other groups, whereas serum IL-6 levels in the LPS and LPS + β-glucan groups at 12 h were significantly decreased. The mean histopathological damage score of the LPS group was slightly higher than that of the LPS + β-glucan group. Moreover, mortality rate was significantly decreased in the LPS + β-glucan group versus the LPS group.β-glucan reduces endotoxemia-induced mortality and might be protective against endotoxemia-induced lung damage.

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 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).

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.

Exposure to carbon tetrachloride (CCl4), a well-known toxicant, causes tissue damage by inducing oxidative stress via formation of free radicals. The fundamental structure of the organs of rats and humans is similar, so administration of CCl4 to rats is an accepted experimental model to produce oxidative damage to various tissues including pulmonary tissue. In this study, we evaluated the protective capacity of melatonin and quercetin against CCl4-induced oxidative lung damage in rats.Rats were divided into five groups each containing seven rats as follows: Control group, Olive oil group CCl4 group, CCl4+Melatonin, and CCl4+Quercetin group. The tissue samples were processed by routine histological and biochemical procedures. Sections were stained with Hematoxylin-eosin and Masson's trichrome. Histopathologic damage score was calculated. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) activities were assayed.The lung sections of control groups showed normal histological characteristics. Fibrosis, interstitial hemorrhage, epithelial desquamation in bronchiole and alveoli, intra-alveolar edema, leukocyte, and macrophage infiltration were observed in lung sections of rats exposed to CCl4 alone. The findings were reduced in the treatments groups. The MDA level in the CCI4 group were significantly higher than in the other groups (p.001), and the CAT and GSH levels in the CCI4+Mel and CCI4+Quer groups were significantly higher than in the CCI4 group (p.05).In conclusion, we suggest that agents with antioxidant properties such as melatonin and quercetin may have positive effects in the treatment of pulmonary diseases characterized by especially edema, inflammation, and fibrosis.

Age-related myocardial dysfunction has important implications with impaired redox homeostasis. Current study focused on investigation of redox homeostasis and histopathological changes in the myocardium of mimetically (MA), naturally aged (NA), and young control (YC) rats. Chronic D-galactose administration to young male Wistar rats (5 months old) was used to set up experimental aging models. We investigated 16 different oxidative damage biomarkers which have evaluated redox homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a protein oxidation biomarker, advanced oxidation end products, protein carbonyl groups, protein-bound advanced glycation end products, dityrosine, kynurenine, and N-formylkynurenine concentrations in MA and NA rats were found to be significantly higher compared to those in YC rats. On the other hand, the levels of protein thiol groups were not significantly different between groups, whereas lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and malondialdehyde in MA and NA rats were found to be significantly higher in comparison to those in YCs. For the assessment of oxidative DNA damage, we analyzed eight hydroxy-5'-deoxyguanosine concentrations of MA and NA groups which were higher than YCs. As an antioxidant status in the MA and NA groups, Cu-Zn superoxide dismutase, ferric reducing antioxidant power, and total thiol levels were lower than those in the YCs. Only nonprotein thiol levels were not significantly different. We also observed similar histopathological changes in MA and NA rats. We concluded that the mimetic aging model could be considered as a reliable experimental model for myocardial senescence. Türkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tübitak ) İstanbul Üniversitesi

ulkay, muzaffer basak/0000-0002-0928-0462; Kaplan, Suleyman/0000-0003-1477-5002; WOS: 000327321900019 PubMed: 23735011 Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) can have adverse effects for in both mother and fetus following administration during the prenatal period. If given during pregnancy, diclofenac sodium (DS), an NSAID, is given during the pregnancy, may also affect the development of the central nervous system (CNS) or related structures. Methods: Pregnant rats were separated into pure control (PG), saline (SG) and diclofenac groups (DG). A daily dose of 1 mg/kg of DS and 1 mL/kg saline was injected intraperitoneally to the DG and SG groups, respectively, from the 5th gestation day for a 15 day of period; the PG group received no treatment. After spontaneous delivery, female offspring were obtained from all groups. After the 20th week of postnatal life, the animals (n = 6 for each group) were perfused and the right optic nerves were resected. Sections were subjected to stereological and histological analysis. Results: There were no significant differences (p > 0.05) between PG, SG and DG groups with respect to myelin thickness, axonal cross-sectional area, axon numerical density, total section area of optic nerve and axon number. Conclusions: Histological and stereological results indicated that treatment with DS or saline produced undesirable effects on female rat optic nerve development and myelinization with respect to morphology.

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.

The liver continuously produces free radicals and reactive oxygen species (ROS) as part of metabolic process. These free radicals are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous nonenzymatic antioxidants like flavonoids. In this study, we have evaluated effects of melatonin and caffeic acid phenethyl ester (CAPE) to young and aged rat liver. Aging-related hepatic changes examined by light and electron microscopy and biochemical methods. Melatonin and CAPE decreased tissue malondialdehyde (MDA) levels in aged rats. Melatonin elevated tissue glutathione peroxidase (GSH-Px) activity and tGSH level, whereas CAPE elevated tissue catalase activity in aged rats. This study demonstrates that both melatonin and CAPE are beneficial in delaying age-related hepatocellular changes. Melatonin and CAPE supplementation in older ages may support liver to protect itself from various damaging agents including infectious agents and toxins.

Sindirim kanalının epitelyal bileşenleri endodermden, bağ dokusu ve kas dokusu ise mezodermden köken alır. Primitif sindirim kanalı 4. haftada embriyonun sefalokaudal ve lateral yönlerden katlanması sonucu vitellus kesesinin bir bölümünün embriyo bedeni içerisinde kalmasıyla gelişmeye başlar. Organ gelişimi hücre çoğalması, farklılaşması, göçü, doku gelişimi ve farklılaşması gibi çeşitli olayları içeren histolojik ve histokimyasal farklılaşma ile karakterizedir. Sindirim sistemine ait organların gelişimi ile ilgili histolojik çalışmalar bulunmakla birlikte, bir bütün olarak sindirim sisteminin prenatal ve postnatal gelişimini kapsayan sınırlı sayıda çalışma mevcuttur.Çalışmamızda özefagus, mide, duodenum, ileum, kolon, karaciğer ve pankreasın prenatal ve postnatal gelişimi ışık mikroskopik düzeyde incelenmeye çalışıldı. Bu amaçla 27 adet Wistar albino dişi sıçan prenatal 7, 10, 14, 17 ve 20 günlük fetüsleri, postnatal 5, 10, 15 ve 20 günlük yavruları içeren grupları oluşturmak üzere gebe bırakıldı. Son grup ise genç erişkin dişi sıçanlardan oluşmaktaydı. Her gruptan 7 adet sıçan incelemeye alındı. Örnekler rutin doku takip işlemlerinden geçirilerek parafine gömüldü. Parafin bloklardan alınan 4 ?m kalınlığında seri kesitlere Mayer'in hematoksilen-eosin metodu, Masson-trikrom metodu ve Periyodik Asit Schiff metodu uygulandı.Özefagus, mide ve bağırsaklar yerleşimleri ve histolojik özellikleri açısından değerlendirildi. Yüzey epitelinin, bezlerin, bağ dokusu ve kas dokusunun, sinir pleksuslarının gelişimi ve farklılaşması incelendi. Karaciğer ve pankreas ise hücresel farklılaşma ve histolojik yapılanma açısından değerlendirildi. Organların histolojik özelliklerinin gelişim dönemleri belirlendi. Memeli hayvanlar olmalarına rağmen Wistar albino sıçanların sindirim sistemlerinin gelişim ve farklılaşma yönünden insanlardan bazı farklılıklar gösterdiği sonucuna varıldı.Anahtar kelimeler: Bağırsaklar, gelişim, karaciğer, mide, özefagus, pankreas, postnatal, prenatal. Epithelial components of digestive tract is derived from endoderm whereas, connective tissue and muscle tissue are derived from mesoderm. Primitive digestive tract begins to develop by sefalokaudal and lateral folding of embryo causing internalization of a part of yolk sac into embryo body during in utero 4th. week. Organ development is characterized by histological and histochemical differentiation including cell proliferation, differentiation, migration, tissue development and differentiation. Although there are some studies about the development of the organs of digestive system; there are limited numbers of studies about the prenatal and postnatal development of the whole digestive system.In our study prenatal and postnatal development of osephagus, stomach, duodenum, ileum, colon, liver and pancreas at light microscopic level was aimed to investigate. Fort this purpose, 27 Wistar albino rats were subjected to pregnancy in order to obtain prenatal 7, 10, 14, 17 and 20 day old fetuses and postnatal 5, 10, 15 and 20 day old newborns. The last group included young adult female rats. Seven rats from each group were subjected to investigation. The samples were embedded into paraffin after routine tissue processing procedures. Serial 4 ?m sections obtained from parafin blocks were stained with Mayer?s hematoxylen, Masson?s Trichrome and PAS staining methods.Osephagus, stomach and intestines were evaluated regarding to their localization and histological features. The development and differentiation of surface epithelium, glands, connective tissue, smooth tissue and nerve plexuses were investigated. In the other hand, the liver and pancreas were evaluated regarding their cellular differentiation and histological characterization. The developmental stages of organs were determined. It is concluded that the digestive system of Wistar albino rats regarding to development and differentiation was different from that of humans in some aspect although they are mammalian animals.Key words: İntestines, development, liver, stomach, osephagus, pancreas, postnatal, prenatal. 287

Recently the authors have reported the potent beneficial effect of caffeic acid phenethyl ester (CAPE) on cholestatic oxidative liver injury induced by acute bile ligation in Swiss albino rats. Herein, they report the ultrastructural hepatocellular alterations induced by acute bile duct ligation and the effect of CAPE administration on these alterations. Bile duct ligation resulted in many degenerative changes, such as vacuolization, mitochondrial degeneration, endoplasmic reticulum dilatation, and lysosome accumulation within the cytoplasm of hepatocytes. Mitochondrial degeneration was also observed within the cytoplasm of the cells of biliary ductular epithelium. CAPE potentially protected the hepatocytes from the cholestasis-induced cellular injury.

Caffeic acid phenethyl ester (CAPE) has been subjected to considerable investigations that have revealed its antioxidant and anti-inflammatory activities in different conditions. But there is not a previous investigation about its effect on cholestatic liver injury. The aim of this study was to investigate the effect of CAPE in rat liver against cholestatic liver injury induced by bile duct ligation.Swiss-albino rats were recruited in the study as follows; Group 1 rats subjected to simple laparotomy known as the sham group; Group 2 rats subjected to bile duct ligation (BDL); Group 3 bile duct ligated rats treated with CAPE. The third group received CAPE (10 micromol/kg) intraperitoneally daily throughout 14 d.Data showed a decrease in gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase levels (ALT) of the CAPE treated rats, compared with BDL group (P0.001, P0.01, and P0.02, respectively). In the CAPE treated rats, tissue levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were significantly lower than that of the BDL group (P0.001). The levels of glutathione (GSH) in CAPE treated rats were significantly higher than that of BDL group (P0.001). In CAPE treated group, the levels of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) were significantly lower than that of BDL group (P0.03, P0.02, respectively). Administration of CAPE in the rats with biliary obstruction resulted in inhibition of necro-inflammation.These results suggest that treatment of CAPE maintains antioxidant defenses, reduces oxidative liver injury, cytokine damage, and necro-inflammation in bile duct ligated rats. Thus, CAPE seems to be a promising agent for the attenuation of cholestatic liver injury.

Pek çok hastalığa zemin hazırlayan önemli bir faktör olan stresin neden olduğu hastalıklardan birisi de gastrik ülserdir. Mekanizması tam olarak aydınlatılmamış olan stres ülserinin patogenezinin multifaktöriyel olduğu kabul edilmektedir. Oksijen radikalleri mukoza hasarının patogenezinde rol aldıkları bilinen bileşiklerdir. Çeşitli stres modellerinin reaktif oksijen türleri (ROS) oluşumunu hızlandırdığı gösterilmiştir. Bu çalışmanın amacı, sıçanlarda açlık, soğuk stres ve hareketsizlik stresi ile oluşturulan gastrik hasarı engellemede antioksidan özellikleri bilinen maydanozun (Petroselinum crispum), melatoninin, beta-karotenin, askorbik asitin ve bir proton pompa inhibitörü olan lansoprazolün etkinliklerini karşılaştırmalı olarak araştırmaktır.Çalışmada 72 adet Wistar albino erkek sıçan 9 gruba ayrıldı: Grup 1: Kontrol, Grup 2: Stres, Grup 3: Stres+normal diyet (7 gün), Grup 4: Stres+serum fizyolojik (0,5 ml/ ip/ 7 gün), Grup 5: Stres+maydanoz (28 g/kg/ diyete ek olarak 7 gün), Grup 6: Stres+melatonin (20mg/ kg/ ip/ 7 gün), Grup 7: Stres+beta-carotene (5 mg/ kg/ gavaj/ 7 gün), Grup 8: Stres+askorbik asit (5 mg/ kg/ ip/ 7 gün) ve Grup 9: Stres+lansoprazol (0,5 mg/ kg/ gavaj/ 7 gün). Denekler 72 saat açlığı takiben +4 derecede 8 saat süreyle hareketsiz kılınarak strese maruz bırakıldılar. Doku örnekleri %10'luk nötral formalinde fikse edildi ve parafine gömüldü. Kesitler hematoksilen-eozin, PAS-Alsiyan mavisi ve Masson'nun trikrom boyası ile boyandı. Histopatolojik hasar indeksi, malondialdehit (MDA) ve glutatyon (GSH) seviyeleri, süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GSH-Px) aktiviteleri ölçüldü.Ortalama histopatolojik hasar skoru kontrol grubunda 1.5 ± 0.22 iken, stres uygulanan grupta 7.0 ± 0.57 idi (P < 0,005). Stres grubunda mukoza bütünlüğünün bozulduğu, epitelin yassılaştığı, lümene döküldüğü, bez yapısının bozulduğu, mukus tabakasının inceldiği ve dejenere alanlarda genellikle homojen bir materyalin biriktiği izlendi. Lümende çok miktarda hücresel artık görüldü. Stres grubu hariç tüm gruplarda histopatolojik skor düştü. Kontrol grubu ile stres grubu arasında doku MDA seviyesi ve CAT aktivitesinde istatistiksel olarak anlamlı fark bulundu (sırasıyla P< 0.005, P< 0.05). Stres grubunda GSH seviyesi ve SOD ve GSH-Px aktiviteleri düşüktü. Maydanoz uygulamasından sonra histopatolojik skor ve MDA seviyesi düşerken (P< 0.05), SOD (P< 0.05) ve CAT aktiviteleri ile GSH seviyesi (P< 0.05) arttı. Lansoprazol histopatolojik skorda (P< 0.005) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde ve SOD ve CAT aktivitelerinde artışa yol açtı. Melatonin histopatolojik skorda (P< 0.005) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde ve GSH-Px ve SOD (P< 0.05) aktivitelerinde artışa yol açtı. Askorbik asit histopatolojik skorda (P< 0.05) ve MDA seviyesinde (P< 0.05) düşüşe, GSH seviyesinde (P< 0.05) ve SOD (P< 0.05) ve GSH-Px aktivitelerinde artışa neden oldu. Beta-karoten uygulaması ise histopatolojik skorda (P< 0.05) ve MDA seviyesinde (P< 0.005) düşüşle, GSH seviyesinde ve SOD ve GSH-Px aktivitelerinde artışla sonuçlandı.Uyguladığımız tüm tedavi edici ajanların strese bağlı olarak ortaya çıkan gastrik hasarın giderilmesinde hücresel antioksidan savunma sistemini destekleyerek yararlı olduğu düşüncesindeyiz.Anahtar kelimler: Askorbik asit, beta karoten, lansoprazol, maydanoz, melatonin, mide, oksidatif stres, sıçan, soğuk stres. Gastric ulcer is one of the diseases caused by stress that is an important underlying factor for many diseases. The pathogenesis of stress-induced ulcer is to be considered multifactorial since its mechanism is not clear yet. Oxygen radicals have been known to be involved in the pathogenesis of gastric mucosal injury. Several stress ulcer models have been shown to increase the production of free oxygen radicals. The aim of the present study was to assess the antioxidative effects of parsley (Petroselinum crispum), melatonin, beta-carotene, ascorbic acid and, lansoprazole , a proton pomp inhibitor on stress-induced gastric mucosal injury.In the present study 72 Wistar albino male rats were divided into nine groups: Group 1: Control, Group 2: Stress, Group 3: Stress+ normal diet (7 days), Group 4: Stress+ saline (0,5 ml/ ip/ 7 days), Group 5: Stress+parsley (diet with extra 28 g/kg/7 days), Group 6: Stress+ melatonin (20 mg/ kg/ ip/ 7 days), Group 7: Stress+beta-carotene (5 mg/ kg /gavage/ 7 days), Group 8: Stress+ascorbic acid (15mg/ kg/ ip/ 7 days) and Group 9: Stress+lansoprazole (0,5 mg/ kg/ gavage/ 7 days). Stress ulcer was induced by the cold-restraint and immobilization method for 8 hours at 4°C after a starvation period of 72 hours. Tissue samples were fixed in %10 neutral buffered formalin and were embedded in parafin. Sections were stained with hematoxylin-eosin, Periodic acid Schiff-Alcian blue and Masson?s trichrom. Histopathologic damage score, malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were assayed.Main histopathological damage score in control group was 1.5 ± 0.22, in stress group 7.0 ± 0.57 (P < 0,005). In stress group, mucosal integrity was damaged, epithelium was flattened and spilled into the gastric lumen, glandular structure was destroyed, the thickness of mucous layer was diminished and a homogenous material was accumulated within the degenaration area. High amount of debris was observed within the lumen. Histopathological damage score was decreased in all of the groups except stress group. MDA level and CAT activity were significantly different between control and stress groups (P< 0.005, P< 0.05; respectively). Parsley administration resulted in decreases in histopathological damage score and MDA level (P< 0.05) and increases in GSH level (P< 0.05) and SOD and CAT (P< 0.05) activities. Lansoprazole decreased histopathological damage score (P< 0.005) and MDA level (P