Usnea longissima, a medically important lichen growing up in forests in Anatolia (Turkey). In this study, the gastroprotective effect of usnic acid (UA) was investigated using an indomethacin (IND)-induced gastric ulcer model in rats. While 25, 50, 100 and 200 mg/kg UA doses were dissolved in 2 ml of olive oil (OO) and administered to rats, only OO was given to one group. In addition, lansoprazole (LAN) and ranitidine (RAN) and IND were dissolved in water and administered to rat groups. IND administration caused very high levels of damage to rat stomachs. On the other hand, when four doses of UA, OO, RAN and LAN were administered, it was determined that hyperemias in the stomach of rats was significantly reduced. After macroscopic analysis of gastric tissues, the activities of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (iNOS and cNOS) enzymes as well as glutathione (GSH) and lipid peroxidation (LPO) levels were determined in these tissues. After IND application, it was detected increases in MPO, CAT and iNOS activities in gastric tissues and decreases in SOD, cNOS and GSH amounts. Four doses of UA, OO, RAN and LAN applications reversed the trend, bringing them closer to healthy levels.

In this study, total antioxidant activity (TAC), phenolic compound amounts (TPC) and reduction power (RP) of Syzygium aromaticum and Glycyrrhiza glabra species, widely used worldwide and our country, were investigated. Ethanol-water and methanol extracts of each type of spice samples were obtained by using the literature methods. In the ethanol-water extracts of S. aromaticum and G. glabra the TAC levels were determined to be at the highest level. When the TPC and RP between extracts listed, it was detected as methanol < ethanol-water. It was concluded that types of spices used as experimental materials thanks to TAC, TPC and RP could be priority in several in vivo and in vitro biological activity studies.

Background: Veratrum, hellebore is an important plant species of the Liliaceae family and jervine is the characteristic steroidal alkaloid constituent of Veratrum album. Purpose: In the current study, anti-inflammatory and antioxidant effects of jervine isolated from NH4OH-benzene extract of V. album rhizomes were investigated on CAR induced paw edema in rats. Methods/Study design: In inflammatory study, 50, 100, 200 and 400 mg/kg doses of jervine, 25 mg/kg doses of DIC and IND were orally administered, and the volume of the foots were measured up to their knee arthrosis by plethismometer. After one hour of the oral administration of the all treatments, 0.1 ml of CAR solution (1%) was injected into the foot of the all rat groups and the volume of the foots were measured during 5 h after CAR injection. GPx, SOD, GR, MPO, CAT enzymes activities and GSH, LPO levels of the supernatants of paw homogenates and inflammation biomarkers such as TNF-alpha and IL-1 beta in the rats serums were also estimated. Results: According to the present results, jervine exerted 50.4-73.5% anti-inflammatory effects in carrageenan induced paw edema. Inflammation biomarkers such as TNF-alpha, IL-1 beta and MPO that increased by CAR injection were suppressed by the administrations of all doses of jervine, IND and DIC. In all paw tissues, LPO levels as indicator of oxidative tissue damage were found to be high in CAR-treated group and it was found to be decreased in all doses of jervine. Conclusion: Jervine, DIC and IND reduced the negative effects of CAR due to increasing effects on the SOD, CAT, GSH, GPx and GR antioxidants.

Sesame oil (SO) is a component of the traditional health food in India as well as in oriental countries and has long been thought to possess the ability to prevent various diseases. We examined the protective effects of sesame oil against acute gastric mucosal damage induced in rats by nonsteroidal anti-inflammatory drug indomethacin (IND). We also intended to determine the relation between antiulcer effect of SO and its antioxidant properties by biochemical evaluation. In this study a total of 5 rat groups were used for ulcer experiment. Antiulcer effects of SO have been investigated on 24 hour fasted 5 rat groups with indomethacine (IND)-induced ulcer model in the presence of positive (Famotidine, FAM), negative (untreated IND group) and intact control groups. In ulcer experiments, two doses of SO exerted significant anti-ulcerogenic effects. In gastric tissues, sesame oil administration decreased the level of LPO and activities of CAT, GR, MPO which were increased after IND application. Furthermore, SO increased the level of GSH which decreased in ulcerous stomach tissues when compared to healthy rat group. We determined that SO has anti-ulcerative effect and this effect are related to antioxidative properties of sesame oil.

N‐acetyl cysteine (NAC), a metabolite of sulphur‐containing amino acid cysteine, is used as an antioxidant and a mucolytic agent. Therefore, we aimed to investigate anti‐inflammatory and anti‐ulcerative effects of NAC. We also intended to determine the relation between antiulcer effect of NAC and its antioxidant properties by biochemical evaluation. In this study a total of 15 rat groups (n = 6 per group) were used for inflammation and ulcer experiments. Anti‐inflammatory effects of NAC have been investigated on six rat groups with carrageenan (CAR)‐induced paw oedema model. Antiulcer effects of NAC have been investigated on 24 h fasted nine rat groups with IND‐induced ulcer model in the presence of positive (LAN, RAN, FAM, and OMEP), negative (untreated IND group) and intact control groups. In biochemical analyses of stomach tissues; glutathione S‐transferase (GST), catalase (CAT), myeloperoxidase (MPO), and superoxide dismutase (SOD) enzyme activities and lipid peroxidation (LPO) and the glutathione (GSH) levels were determined. All doses of NAC exerted significant anti‐inflammatory effect; even the effect of 900 mg/kg NAC was similar with that of DIC and IND. In gastric tissues NAC administration decreased the level of LPO and activity of CAT, which were increased by IND. Furthermore, NAC increased the GSH level and SOD and GST activities, which decreased in ulcerous stomach tissues. Only MPO activity increased in both IND and NAC groups when compared to healthy rat group. We determined that NAC has both anti‐inflammatory and anti‐ulcerative effects. J. Cell. Biochem. 117: 308–319, 2016. © 2015 Wiley Periodicals, Inc.

Two lichen metabolites, rhizonaldehyde (1) and rhizonyl alcohol (2), were isolated from the acetone extract of Lobaria pulmonaria by chromatographic methods, and their chemical structures were determined by UV/VIS, IR, and 1D- and 2D-NMR spectroscopic methods. The gastroprotective and in vivo antioxidant activities of extracts of L. pulmonaria and its metabolites, 1 and 2, were investigated in indomethacin-induced ulcer models in rats. The gastric lesions were significantly reduced by acetone, hexane, and CHCl3 extracts, with 75.3-41.5% inhibition. Rhizonyl alcohol (2) significantly reduced the gastric lesions with an inhibition rate of 84.6-42.8%, whereas rhizonaldehyde (1) significantly increased the gastric lesions. Antioxidant parameters and myeloperoxidase activities were also evaluated in the gastric tissues of the rats. Indomethacin caused oxidative stress, which resulted in lipid peroxidation in gastric tissues by decreasing the levels of the antioxidants as compared to healthy rat tissues. In contrast to indomethacin, all extracts and rhizonyl alcohol (2) caused a significant decrease in lipid peroxidation levels and an increase in antioxidant parameters, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase, and reduced glutathione in gastric tissues. The administration of rhizonyl alcohol (2) also resulted in a decrease in gastric myeloperoxidase activity increased by indomethacin. The gastroprotective effect of rhizonyl alcohol (2) can be attributed to its antioxidant properties and its suppressing effect on neutrophil infiltration into gastric tissues.

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.

The possible role of β -2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β -2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β -2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β -2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β -2 adrenergic receptors in inflammatory and hyperalgesic conditions.

In this study, the antiulcer activity of lacidipine was investigated on indomethacin-induced gastric ulcer model and it was examined whether the antiulcer effect of lacidipine was related to oxidant/antioxidant parameters in rats. Anti-ulcerative effects of lacidipine were investigated on an indomethacin-induced gastric ulcer model in rats. The antiulcer capability of lacidipine was compared to 20 mg kg(-1) famotidine. Results showed that lacidipine prevented the formation of indomethacin-induced ulcers at 2 and 4 mg kg(-1) doses significantly. Enzymatic and non-enzymatic antioxidant parameters, such as total glutathione, superoxide dismutase and glutathione peroxidase, were found low and enzymatic and non-enzymatic oxidant parameters, such as myeloperoxidase and malondialdehyde, were found high in the gastric tissues of indomethacin-given rats. Indomethacin acts through not only the inhibition of the synthesis of cytoprotective prostaglandins but also by affecting enzymatic and non-enzymatic, oxidant and anti-oxidant mechanisms.

The aim of this study was to determine the effects of diabetes mellitus, ovarian aging, ovarian aging plus diabetes mellitus, and the oxidative stress generated by these conditions on the lungs of rats, using histopatological and biochemical parameters. In the diabetic group, some abnormalities like bronchial hyperplasia, edema, haemorrhage, pulmonary capillary dilatation, breakdown of alveoli, mononuclear inflammatory cells, and moderate immunoreactivity were observed. Although, the results obtained from the ovariectomy group were similar to those of the diabetic group, haemorrhagic area and an increase in apoptotic cell density were observed more in this group compared to the diabetic group. In the last group, both immunoreactivity rate and the degree of abnormal structure were more remarkable compared to the other groups. Our biochemical results confirmed the histological findings. Conclusively, increase in the reactive oxygen species (ROS) levels of the cell, regardless of whatever reason, may lead to many other functional failures as well produce some disease conditions. Our results suggested that oxidative load increased in rats with ovariectomy-induced menopause with or without diabetes; however, enzymatic free radical defense mechanisms were damaged in the diabetic rats. The results also suggested that the antioxidant ability of the female sex hormone acts as a protective factor against diabetes.

We aimed to investigate how Diabetes Mellitus (DM) affects myeloperoxidase activity, antioxidant status, and lipid peroxidation using biochemical approaches in heart, liver, and lung and serum cytokine analyses, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in rat with sepsis induced by a cecal ligation and puncture-induced (CLP) sepsis. The rats were divided into four groups: control group, diabetic group, sepsis group, and diabetic+sepsis group. DM was induced in the male Wistar albino rats by administration of alloxan. Polymicrobial sepsis was induced by cecal ligation and two-hole puncture. After alloxan administration, all groups of rats were allowed to recover for 1 month. CLP model was applied after 1 month recovery to group 3 and 4. IL-6 and TNF-α, were measured. Effects of antioxidant defenses on the DM and/or sepsis process, the antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) were evaluated in heart, lung and liver tissues. The oxidant levels, such as lipid peroxidation (LPO) and myeloperoxidase (MPO) levels were also evaluated in tissues. We demonstrated DM to augment the level of oxidant and proinflammatory cytokines in lung, liver, and heart and also to exacerbate oxidative injury as assessed by increased LPO and MPO, and decreased GSH and SOD levels in a sepsis model. DM increased levels of proinflammatory cytokines while DM also resulted in significantly increased levels of proinflammatory cytokines following CLP. DM-increased plasma proinflammatory cytokines levels correlated positively with tissue oxidant levels, such as MPO and LPO levels in a rat abdominal sepsis model, based on CLP, which resulted in the exacerbation of oxidative organs injury.

Gastroprotective effects of α-lipoic acid (ALA) against oxidative gastric damage induced by indomethacin (IND) have been investigated. All doses (50, 75, 100, 150, 200, and 300 mg/kg body weight) of ALA reduced the ulcer index with 88.2% to 96.1% inhibition ratio. In biochemical analyses of stomach tissues, ALA administration decreased the level of lipid peroxidation (LPO) and activities of myeloperoxidase (MPO) and catalase (CAT) in gastric tissues, which were increased after IND application. ALA also increased the level of glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) that were decreased in gastric damaged stomach tissues. In conclusion, the gastroprotective effect of ALA could be attributed to its ameliorating effect on the antioxidant defense systems.

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

BACKGROUND:Diabetes mellitus (DM) has a negative effect on cardiovascular functions. Little, however, is known of the overall effect of DM on the cardiac histology or the pathophysiological basis of this.AIM:We aimed to investigate the role of oxidative stress on the pathogenesis of diabetic cardiomyopathy in an experimental model.MATERIALS AND METHODS:12 week-old female Sprague Dawley rats were randomly allocated into a healthy control group (n=6) and an DM group (n=6). After 12 weeks of alloxan induced DM, the groups' cardiac tissues were histopathologically analyzed and examined for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of reduced glutathione (GSH) and lipid peroxidation (LPO)].RESULTS:When compared to the control group, the DM group showed cardiomyopathic changes. In the DM group, activities of CAT (144 +/- 0.9 vs. 112 +/- 1.4, p < 0.05) and LPO amount (27.0 +/- 0.74 vs. 14.4 +/- 0, 20, p < 0.05) were significantly increased whereas activities of SOD (142 +/- 0.2 vs. 146 +/- 0.7, p < 0.05) and amount of GSH (3.48 +/- 0.01 vs. 3.73 +/- 0.01, p < 0.05) were significantly decreased when compared to the control group. Besides, activities of MPO (7.3 +/- 0.02 vs. 8.6 +/- 0.11, p < 0.05) were comparable between groups.CONCLUSIONS:Using the experimental animal model, we were able to demonstrate that DM causes cardiomyopathic changes, and we propose that these changes could be mediated by an oxidative stress.

Objective: To evaluate the effects of growth hormone (GH) as an antioxidant and tissue-protective agent and analyse the biochemical and histopathological changes in rat ovaries due to experimental ischemia and ischemia/reperfusion injury.Study design: Forty-eight adult female rats were randomly divided into eight groups. In Group 1, a period of bilateral ovarian ischemia was applied. In Groups 2 and 3, 1 and 2 mg/kg of GH was administered, and 30 min later, bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 1 and 2 mg/kg of GH, respectively, 2.5 h after the induction of ischemia. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. Group 7 received a sham operation plus 2 mg/kg of GH. Group 8 received a sham operation only. After the experiments, superoxide dismutase and myeloperoxidase activity and levels of glutathione and lipid peroxidation were determined, and histopathological changes were examined in all rat ovarian tissue.Results: Ischemia and ischemia/reperfusion decreased superoxide dismutase activity and glutathione levels in ovarian tissue, but increased lipid peroxidation levels and myeloperoxidase activity significantly in comparison to the sham group. The 1 and 2 mg/kg doses of GH before ischemia and ischemia/reperfusion decreased lipid peroxidation levels and myeloperoxidase activity in the experimental groups. The administration of GH before ischemia and ischemia/reperfusion treatments also increased superoxide dismutase and glutathione levels. The histopathological findings also suggested a protective role of GH in ischemia/reperfusion injury. That is, ovarian tissues in the ischemia groups showed histopathological changes, such as haemorrhage, cell degeneration, and necrotic and apoptotic cells, but these changes in the GH groups were lesser. Moreover, in the ischemia/reperfusion groups, acute inflammatory processes such as neutrophil adhesion and migration, apoptotic and degenerative cells, stroma I oedema and haemorrhage - were present. However, the ovarian tissues of the IR + GH (1 mg) group had minimal apoptotic cells, and the IR + GH (2 mg) group had no apoptotic cells. In addition, the general ovarian histological structures of these groups were similar to those of the healthy control group.Conclusions: The administration of GH is protective against ischemia and/or ischemia/reperfusion-induced ovarian damage. This protective effect can be attributed to the antioxidant properties of GH. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

A gastroprotective effect occurs when α2 receptors are innervated. The dextro isomer of medetomidine, dexmedetomidine, is a highly selective α2-adrenoreceptor agonist. The aim of this study was to investigate whether dexmedetomidine has an antiulcerative effect and to show whether the antiulcer mechanism of dexmedetomidine is linked with oxidant/antioxidant parameters. The antiulcerative effect of dexmedetomidine was studied in an indomethacin-induced ulcer model, and some oxidant/antioxidant parameters were measured in these gastric tissues. Whereas the average ulcerous areas for the groups that received 10, 25, 50, and 100 μg/kg dexmedetomidine doses were 29±4.2,8±2.1,0±0 and 0 ± 0 mm2, respectively, the ulcerous area was 52.1 ± 4.5 mm2 in the indomethacin control group and 0.5 ±0.2 mm2 in the famotidine group. In conclusion, the α2-adrenoreceptor agonist dexmedetomidine showed a significant antiulcerative effect in rat gastric tissue at all doses. This antiulcerative effect is stronger with increasing dosage; at the 50 and 100 μg/kg doses, no ulcerous areas were observed. In light of these results, we conclude that there is a correlation between antiulcer mechanisms and α2-receptor activation. In rats given dexmedetomidine, all of the investigated antioxidant parameters increased, except for catalase (CAT). Conversely, aside from myeloperoxidase (MPO), all oxidant parameters decreased. Therefore, oxidant/antioxidant parameters play a role in the antiulcer mechanism of dexmedetomidine.

Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD-treated CLP group; (iii) CLP group; and (iv) sham-operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil-treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham-operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)-α level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP-induced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-α.