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What is the central question of this study? We evaluated the effects of diabetes and exercise on lipopolysaccharide-induced acute lung injury. By providing a comprehensive analysis of redox status, blood gases and histological parameters, we aimed to contribute to the ongoing debate in the literature. What are the main findings and its importance? We demonstrated the preventive effect of exercise, but diabetes did not alter the severity of acute lung injury.Acute lung injury (ALI) is a life-threatening respiratory condition. Diabetes (DM) is a metabolic disease characterized by hyperglycaemia. There is an ongoing debate concerning whether there is a protective effect of diabetes in ALI. Exercise is a special type of physical activity that has numerous beneficial effects. The aim of our study was to investigate the effects of diabetes and exercise on the prognosis of ALI. Male Wistar albino rats were divided into two groups (sedentary and exercise). Both groups were divided into four subgroups: Control, ALI, DM, DM+ALI (n = 6 each). Diabetes was induced by injection of streptozotocin (50 mg/kg i.p.). The maximal exercise capacity was determined with the incremental load test. Animals were exercised on a treadmill for 45 min at 70% of maximal exercise capacity, 5 days a week for 12 weeks. Acute lung injury was induced by intratracheal injection of lipopolysaccharide (100 μg/100 g body weight) 24 h before the end of the experiment. We performed arterial blood gas analysis. Redox status was measured in both plasma and lung tissue. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels were measured in lung tissue. Lung tissue was evaluated histologically. Acute lung injury caused significant damage in the lung tissue, which was verified histologically, with an increase in oxidative stress parameters. Exercise prevented the lung damage induced by ALI and reduced oxidative stress in the lung tissue. Diabetes did not alter the magnitude of damage done by ALI. Exercise showed a protective effect against DM and ALI in rats. The effect of DM was insignificant for the prognosis of ALI.

Aging in humans represents declining in cardio-protective systems, however its mechanisms are not known yet. We aimed to analyse how aging affects key mechanisms responsible for contractile dysfunction via comparing the improperly synchrony between electrical and mechanical activities in male aged-rats (24-month old) comparison to those of adult-rats (6-month old). We determined significantly increased systemic oxidative stress with decreased antioxidant capacity, clear insulin resistance and hypertrophy in aged-rats with normal fasting blood glucose. We also determined significantly high level of reactive oxygen species, ROS production in fluorescent dye chloromethyl-2′,7′-dichlorodihydrofluoroscein diacetate (DCFDA) loaded isolated cardiomyocytes from aged-rats, confirming the increased oxidative stress in these hearts. In situ electrocardiograms, ECGs presented significant prolongations in RR- and QT-intervals in the aged-rats. Invasive hemodynamic measurements demonstrated marked increases in the heart rate and mean arterial pressure and decreases in the ejection-fraction and preload-recruitable stroke-work, together with depressed contraction and relaxation activities in aortic rings. In light and electron microscopy examinations in aged-rats, significant increases in muscle fibre radius and amount of collagen fibres were detected in the heart as well as markedly flattened and partial local splitting in elastic lamellas in the aorta, besides irregularly clustered mitochondria and lysosomes around the myofilaments in cardiomyocytes. MitoTEMPO treatment of tissue samples and cardiomyocytes from aged-rats for 1-h induced significant structural improvements. In the second part of our study, we have shown that mitochondria-targeted antioxidant MitoTEMPO antagonized all alterations in the heart samples as well as penylephrine-induced contractile and acetylcholine-induced relaxation responses of aged-rat aortic rings. Overall, the present data strongly support the important role of mitochondrial oxidative stress in the development of aged-related insufficiencies and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in aging-associated complications.

Objective: The most important issue in flap surgery is flap viability. This study aimed to compare the effects of most commonly used phosphodiesterase type 5 (PDE5) inhibitors on flap survival. Methods: A 3 x 9 cm flap was elevated from the dorsum of 32 Wistar albino rats. In the control group, saline was administered 2 hours before the flap elevation and continued for 2 days after the surgery. In the sildenafil, tadalafil, and vardenafil groups, the related drug was administered. Blood flow in the flaps was monitored with laser Doppler flowmetry. On postoperative day 7, flaps were photographed and biopsies were obtained. Results: The ratios of flap necrosis area in the tadalafil, sildenafil, and vardenafil groups were lower than that in the control group, but without significant difference (p = 0.077). Histopathological evaluation revealed no significant difference among the groups. Conclusion: The ratio of flap necrosis area tended to be lower in the groups receiving oral PDE5 inhibitors than in the control group, although not statistically significant. The role of PDE5 inhibitors needs to be evaluated in larger studies before a conclusion can be made regarding their effects on flap viability.

High glucose and increased oxidative stress levels are the known important mediators of diabetic nephropathy. However, the effects of these mediators on tissue damage basically due to extracellular matrix expansion in mesangial cells have yet to be fully examined within the context of early stage diabetic nephropathy. In this study, we attempted to characterize changes in mesangial cells of streptozotocin-induced diabetic rats with a comparative investigation of kidney tissue by using different microscopy techniques. The serum levels of urea and creatinine of diabetic rats, as biomarkers of kidney degeneration, decreased significantly compared to those of age-matched controls. In diabetic rats, there are increased malondialdehyde and oxidized-glutathione levels as well as reduced-glutathione and glutathione-peroxidase activity levels in renal tissue compared to those of the controls. By using light and electron microscopies, we showed that there were marked thickening in Bowman's membrane and glomerular capillary wall, increased amount of extracellular matrix often occupying Bowman's space, degenerations in tubules, an increased number of mesangial cells in the network of glomerular capillary walls, and increased amount of lipid accumulation in proximal tubules in the renal tissue of diabetic rats. Our confocal microscopy data confirmed also the presence of irregularity and widened in glomerular capillaries, their attachment to the Bowman's capsule, degenerated heterochromatin, thickening in foci of glomerular basement membrane, and marked increase in mesangial cells. These results suggest that a detailed structural investigation of kidney tissue provides further information on the important role of mesangial cells in pathogenesis of diabetic nephropathy.

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We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 micromol/kg/d, intra peritoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.

In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg(-1) rat day(-1); orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme activities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung. Copyright (c) 2004 John Wiley & Sons, Ltd.

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 micromol/kg body wt/d sodium selenite (Na2SeO3) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.

The factors with increasing diabetes-prevalence lead to significant global increases in chronic kidney disease. Since hyperglycemia generates more ROS and attenuates cellular antioxidant-defense mechanisms, numerous studies demonstrated that hyperglycemia-induced oxidative stress played a major role in the extracellular matrix expansion in tissues. Although no direct relation between activation of beta-adrenergic (beta-AR) system and kidney disease in diabetes and since beta-blockers demonstrate marked beneficial effects due to their scavenging free radicals and/or acting as an antioxidant in diabetic animal studies, the eventual objective of the present study was to determine whether timolol-treatment of streptozotocin-induced diabetic rats (5 mg/kg, daily following diabetes-induction, for 12-week) has advantage to prevent hyperglycemia-induced renal-damage via enhancing the depressed antioxidant defense in the kidney. Light microscopy data and their quantification demonstrated that timolol-treatment prevented basically glomerular hypertrophy, expansion in mesangium cell size, thickening and fibrosis in glomerular basement membrane, and accumulation of glycogen into tubular epithelial cells. Additionally, electron microscopy data demonstrated that timolol-treatment could also prevent diabetes-induced changes in the kidney tissue such as hypertrophy in podocytes, lost of filtration gaps and slit-diaphragms, and vacuolization in the distal tubular cells. Biochemical analysis basically on enzymes of antioxidant-defense system, including glutathione-S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase, further supported that diabetes-induced damage in the kidney is mostly dependent on the increased oxidative stress and timolol, having an antioxidant-like action, could protect the kidney against hyperglycemia-induced damage without normalization of high-blood glucose level. Consequently, it can be suggested that although beta-blockers are widely used for the treatment of cardiovascular diseases, beta-blocker therapy of diabetics seems to be a new therapeutic approach against hyperglycemia-induced kidney damage in diabetic patients.

Although the neuropathology of ischaemic fibre degeneration is relatively well known, its pathogenesis is poorly understood. One of the presumed mechanisms is oxidative stress, causing the breakdown of the blood-nerve barrier (BNB) and ending in lipid peroxidation. We evaluated the effect of ischaemia and reperfusion on the sciatic-tibial nerve of the rat and investigated the biochemical, pathological, and functional evidence of BNB disruption and lipid peroxidation. The distal portion and trifurcation of the sciatic nerve were rendered ischaemic by clamping the femoral vessels for 3 h and followed by varying durations of reperfusion. Reperfusion resulted in an increase in lipid peroxidation beginning from the first hour and increasing until the seventh day, followed by a gradual decline over the following weeks. Nerve oedema and ischaemic fibre degeneration (IFD) consistently became more severe and prominent with reperfusion, indicating that oxidative stress damages the BNB and causes IFD. Results of functional testing by the sciatic function index correlated with other parameters as walking track analysis results got worse as reperfusion periods increased. Impairment of walking patterns was more striking after the first day and continued up to the third week. These data indicate that severe ischaemia of the peripheral nerve results in reperfusion injury, functional impairment, and disruption of the BNB. Microvascular events, which may occur during reperfusion, may be important in amplifying the nerve fibre degeneration that initiated during ischaemia.

AIM Bacitracin is one of the most frequently used agents for the topical irrigation of the cerebral cortex. The aim of this study is to investigate whether bacitracin has histopathological and ultrastructural effects when applied topically to the cerebral cortex. MATERIAL AND METHODS Twenty-eight rats were randomly assigned to four groups. Except the control group, each rat underwent left frontoparietal craniectomy with dural removal. Then, in the sham group a piece of dry absorbable gelatin sponge was placed over the left hemisphere; in the saline group a gelatin sponge soaked in normal saline; and in the bacitracin group a gelatin sponge soaked in 500 units bacitracin was used. After 48 hours, brain tissues were extracted for histopathological and electron microscopic analyses. RESULTS Among the four groups dark stained neurons were found to be statistically higher in number in the bacitracin group compared with the control, sham and saline groups. Electron microscopic evaluation revealed that, in the bacitracin group, almost all cytoplasmic organelles were poorly preserved. CONCLUSION Topical application of the bacitracin on to the cerebral cortex caused histopathological and ultrastructural changes in the neural tissue. These changes may be an evidence for the neurotoxic effects of bacitracin.

Current data support that pharmacological modulators of endoplasmic reticulum stress (ERS) have therapeutic potential for diabetic individuals. Therefore, we aimed to examine whether timolol, having free radical-scavenger action, besides being a beta-blocker, exerts a cardioprotective effect via inhibition of ERS response in diabetic rats in a comparison with an antioxidant N-acetylcysteine (NAC). Histopathological data showed that either timolol- or NAC-treatment of diabetic rats prevented the changes in mitochondria and nucleus of the cardiac tissue while they enhanced the cellular redox-state in heart as well. The levels of ER-targeted cytoprotective chaperones GRP78 and calnexin, unfolded protein response signaling protein CHO/Gadd153 besides the levels of calpain, BCL-2, phospho-Akt, PUMA, and PML in the hearts from diabetic rats, treated with either timolol or NAC, are found to be similar among these groups, although all these parameters were markedly preserved in the untreated diabetics compared to those of the controls. Taken into consideration how important a balanced-ratio between anti-apoptotic and pro-apoptotic proteins for the maintenance mitochondria/ER function, our results suggest that ERS in diabetic rat heart is mediated by increased oxidative damage, which in turn triggers cardiac dysfunction. Moreover, we also demonstrated that timolol treatment of diabetic rats, similar to NAC treatment, induced a well-controlled redox-state and apoptosis in cardiac myocardium. We, thus for the first time, report that cardioprotective effect of timolol seems to be associated with normalization of ER function due to its antioxidant action in cardiomyocytes even under hyperglycemia.

Nitrogen Mustard (NM) is an alkylating agent that damages cellular nuclear DNA after penetrating tissue. This results in cytostatic, mutagenic and cytotoxic effects. We used the electron microscope to investigate the effect of NM gas administered through the dermal and respiratory routes to rats on the brain cortex and also tried to show whether the antioxidant Proanthocyanidin (PC) could decrease this effect.A total of 32 rats were randomized into four groups: Group I: Control group, Group II: PC group, Group III: NM group, Group IV: NM + PC group. The rats were sacrificed 3 days after NM gas exposure. A segment of the cortical tissue was prepared for electron microscopy.We used the electron microscope for cellular analysis of NM on cortical neural cells. These investigations revealed degeneration of the cortical neural cell nuclei together with oedema and axonal degeneration in the subcortical neural tissue. The group receiving antioxidants was found to have less oedema and degeneration.These findings imply that structural changes induced by mustard gas can be prevented and restored by proanthocyanidin treatment.

To investigate the action of N-acetylcysteine (NAC) on rat isolated ileal contractility, and to determine the effects of NAC on histopathological changes on ileal tissue.The study took place at the Faculty of Medicine, Ankara University, Ankara, Turkey, in January 2003. Adult Wistar rats were used in all experiments. Two groups were designed. The experimental group, to which NAC 0.5 g/Kg/day was administered orally by adding to their water for 7 days, and the control group to which only saline was administered. At the end of the experimental periods, one cm pieces of terminal ileum segments were removed for testing ileal contractility, and one cm pieces of ileum segments were removed for histopathological experiments. The acetylcholine (ACh)-induced contraction was recorded, and the ileal tissue examined using light and electron microscopic technics for histopathological changes.The average peak amplitude of ACh-induced contraction recorded in standard tyrode solution of the experimental group was decreased significantly when compared to the control group in standard and calcium-Free tyrode solution. On histopathological findings, there were swollen mitochondria with disturbed cristae in the ileal muscle.Our data suggest that the NAC in the present experiment decreased the ACh-induced contractility on rat-isolated ileum.

Different forms of Aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Vitamin E (? -tocopherol) is an antioxidative agent that has been reported to be important for detoxification pathways. This study was thus aimed at elucidating the protective effects of vitamin E towards aluminium toxicity on the histology of the rat testis. Al (5 mg/kg body weight) was administered intraperitoneally in 2 ml saline, either alone or immediately before vitamin E (500 mg/kg body weight), at a different point of abdomen, and the alterations in the testis tissue were analyaed histologically. Seven treated animals were sacrificed for each group, with the testes removed and examined histologically. In the Al-treated group, the germinal epithelium of the seminiferous tubules was thinner in places and spermatids were almost absent; sperm numbers were low and there were no sperm in the lumen. In the Al plus vitamin E rats, there were large numbers of spermatids and sperm in the seminiferous tubule lumen. In the vitamin E alone group, a normal histology was seen. Electron microscopically, in the Al-treated group there were irregularities in the nuclear membrane, some damaged mitochondria, a decrease in the number of ribosomes, and an increase in the number of lysosomes in the sertoli cell cytoplasm. In the primary spermatocyte cytoplasm, there was an increase in the rough endoplasmic reticulum. In the Al plus vitamin E group, the spermatogeneic cells and the sertoli cell cytoplasm showed an almost normal appearance. The ultrastructure of the testis in the vitamin E alone group showed a normal appearance. In conclusion, vitamin E antagonizes the toxic effects of Al at the histological level, thus potentially contributing to an amelioration of the testis histology in the Al-treated rats. The associated biochemical parameters merit further investigation. Copyright © American College of Toxicology.

This study investigated the effect of rifampin on the thickness of capsules around silicone implants by bactericidal activity against Stapylococcus epidermidis. Silicone blocks (1 x 1 cm) were placed into pockets created for each of the 40 rats included in the study. In group 1, the operation was performed under aseptic conditions. In group 2, standard S. epidermidis was inoculated into the pocket, whereas rifampin and S. epidermidis were applied in group 3. In group 4, only rifampin was applied topically on implants. After 12 weeks, the peri-implant capsules were removed and examined under a photomicroscope and a scanning electron microscope. The mean thickness of the capsules was 63.307 microm in group 1, 111.538 microm in group 2, 43.076 microm in group 3, and 30.384 mum in group 4. The differences between groups 2 and 3 and groups 2 and 4 were found to be statistically significant (p < 0.001). Rifampin appears to be an agent for preventing peri-implant capsule formation.

Introduction: Our goal was to investigate the effects of arsenic sulfur (AsS) on the detrusor smooth muscle reactivity. Material and Methods: AsS (100 ppm µg/g) in drinking water was administered for 2 weeks to two groups of female Wistar rats. The contractile responses of urinary bladders to electrical field stimulation, carbachol, ATP and KCl, and the relaxant responses to ATP, adenosine and isoproterenol were examined. Urinary bladder strips were collected for light microscopic examination. Results: Our results demonstrate that oral inorganic AsS exposure induced enhanced contractile and reduced relaxant responses in rats. We hypothesize that AsS is involved in deficiencies of isolated urinary bladder in rats. Conclusion: These functional and morphological changes may be important as an intermediate link in urinary bladder oncogenesis induced by AsS.

Can, Belgin/0000-0002-0469-7998 WOS: 000223898600007 PubMed: 15263828 Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46+/-0.45 vs. 0.80+/-0.14 mmol/l, means+/-SD, p

It is known that streptozotocin (STZ)-induced diabetes causes functional and structural alterations in some types of tissue and organ. A number of methods have been used to characterize the properties of diabetic tissues and their diagnosis. Selenium compounds, playing an antioxidant role, can restore some altered metabolic parameters and diminished functions in experimental diabetes. The first aim of the present study was to investigate the effects of STZ-induced diabetes on structural properties of rat long bones. Electron and light microscopic observations showed deleterious alterations in the structure of the diabetic rat long bones, the most prominent effect being in osteocytic cells. Fine cytoplasmic processes of the osteocytes seemed to be shortened, and diabetes affected the normal cytoplasmic processes in a negative manner. The second aim of the present study was to evaluate the effects of sodium selenite treatment for 4 wk on the long bones of the diabetic rats. Electron and light microscopic observations demonstrated that sodium selenite treatment prevented the STZ-induced structural as well as ultrastructural changes in the long bones of the rats. In conclusion, this study first showed that a period of 5-wk diabetes was enough to cause some important and degenerative changes in the structure of the bone tissues, and, second, it demonstrated that sodium selenite treatment of the diabetic rats could normalize these alterations.