1,721,169 research outputs found
Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment
No full textAim: To investigate the effect of tadalafil in rats administered with daily dutasteride. Methods: Twenty-four Sprague-Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D + T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined. Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D + T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p = .01) whereas group D + T had the highest iNOS (p<.001). ELISA revealed similar outcomes in terms of NOS enzyme isoform levels. The mean of smooth muscle to collagen ratio was the lowest in group D (p < .001) and it was similar among group C and group D + T (p = .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D + T (p>.05). Group D and group D + T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D + T. Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis
Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents
No full textThree novel series of 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid derivatives namely 4-substituted-1,2,4-triazoline-3-thiones (4a-g); 2-substituted- 1.3.4-thiadiazoles (5a-g) and 2-substituted- 1,3,4-oxadiazoles (6a-g) have been synthesized. Twenty-one of the newly synthesized compounds were tested against various bacteria, fungi, yeast species and virus. In addition, we have replaced the carboxylic acid group of diflunisal with heterocycles and the anti-inflammatory activity of heterocycles reported here. Compound (5d) showed activity against Escherichia coli Al and Streptococcuspyogenes ATCC-176 at a concentration of 31.25 mu g/mL, whereas cefepime, the drug used as standard, has been found less active against the bacteria mentioned above. Compound (4b) has exhibited activity against Aspergillus variecolor and Trichophyton rubrum at a concentration of 31.25 and 15.25 mu g/mL, whereas Amphotericin B, the drug used as standard, has been found less active against the yeast and fungi. The highest antiviral activity was found in the 1,3,4-thiadiazole derivative (5a) having a methyl group at 2nd position against Sindbis virus at 9.6 mu g/mL. Compound (4c) exhibited the highest anti-inflammatory activity (73.03%) whereas diflunisal, the drug used as standard, has been found less active (24.16%). Compound (5f) presented similar antinociceptive activity with the standard drug (paw withdrawal latency was 19.21 s compared to that of diflunisal which was 19.14 s, in hot plate test). (c) 2007 Elsevier Masson SAS. All fights reserved
Tadalafil Preserves Penile Nitric Oxide Synthase from Detrimental Effect of Paroxetine in Rats
Full text linkObjective: Paroxetine is a commonly prescribed SSRI that can impair erectile function in animal models via inhibition of nitric oxide synthase (NOS). Tadalafil potentiates nitric oxide (NO)-mediated responses in isolated trabecular smooth muscle and penile erection. The purpose of this study was to evaluate the impact of co-administering tadalafil with paroxetine on penile NOS levels in rats. Materials and Methods: A total of 30 male Sprague-Dawley rats were divided into 3 groups as control (Group-C), paroxetine (Group-P) and paroxetine plus tadalafil (Group-P+T). After 28 days of treatment, rats were sacrificed and their penile tissues were harvested for analysis. NOS isoform protein levels and immunoreactivity scores of NOS were assessed. Statistical significance level was set at p<0.05. Results: Neuronal NOS (nNOS) levels were significantly decreased in group-P, compared with group-C (p<0.001). In comparison, rats in group-P+T had significantly higher nNOS levels compared to group-P (p<0.001). Endothelial NOS (eNOS) and inducible NOS (iNOS) levels were significantly higher in group-P compared with group-C (p<0.01). The levels of eNOS and iNOS in group-P+T were similar to group-C. Conclusion: Daily treatment with tadalafil prevented chronic paroxetine-induced changes in all three NOS isoform levels. Tadalafil treatment may therefore be a useful therapy in men with paroxetine-associated erectile dysfunction
Chard (Beta vulgaris var. cicla) extract improved hyperglycemia-induced oxidative stress and surfactant-associated protein alterations in rat lungs
No full textContext: Chard is used as an antidiabetic agent by the diabetic patients in Turkey. Objective: The effect of chard extract [Beta vulgaris L. var. cicla (Chenopodiaceae)] on the antioxidant system and the expression of surfactant-associated proteins (SP) in the lungs of hyperglycemic rats were examined. Materials and methods: Hyperglycemia was induced by a single dose of streptozotocin (60 mg/kg) provided intraperitoneally. Fourteen days after the rats were rendered hyperglycemic, the chard (2 g/kg/d), insulin (6 U/kg/d), and chard plus insulin (as mentioned above) were administered to rats for 45 d. On day 60, rats' lungs were removed. Oxidative stress parameters and SP expression were assayed. Results: The lungs of hyperglycemic rats were characterized by the induced lipid and protein oxidation, elevated myeloperoxidase and xanthine oxidase activities, decreased glutathione levels, and reduced tissue factor and antioxidant enzymes activities (catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase). Chard treatment alone and chard treatment combined with insulin were capable of achieving a regression of pulmonary oxidative stress, by inhibiting lipid and protein oxidation, and restoring the antioxidant system of hyperglycemic rats. SP-A expressions were significantly unchanged in all groups, whereas pro-SP-C and SP-D expressions were reduced in hyperglycemic rats. Pro-SP-C and SP-D levels were increased by chard and insulin administrations alone and combined in hyperglycemic rats. Discussion and conclusion: All treatments have a positive effect on the surfactant and antioxidant systems of the lungs of hyperglycemic rats. The best therapeutic effect was provided by treatment with chard extract alone in the compensation of hyperglycemic symptoms
Chard (Beta vulgaris L. var. cicla) extract ameliorates hyperglycemia by increasing GLUT2 through Akt2 and antioxidant defense in the liver of rats
No full textChard is a plant used as an alternative hypoglycemic agent by diabetic people in Turkey. The aim of this study was to examine the molecular mechanism of hypoglycemic effects of chard extract. Male Sprague-Dawley rats (6-7 months old) were divided into five groups for this investigation: (1) control, (2) hyperglycemic, (3) hyperglycemic+chard, (4) hyperglycemic + insulin, (5) hyperglycemic + chard + insulin. Fourteen days after animals were rendered hyperglycemic by intraperitoneal injection of 60 mg/kg streptozotocin, the chard water extract (2 g/kg/day) or/and insulin (6 U/kg/day) was administered for 45 days. Hypoglycemic effect of chard extract was demonstrated by a significant reduction in the fasting blood glucose and increased glycogen levels in liver of chard extract-treated hyperglycemic rats. Moreover, activity of adenosine deaminase, which is suggested as an important enzyme for modulating the bioactivity of insulin, was decreased by chard treatment. Immunostaining analysis showed increased nuclear translocation of Akt2 and synthesis of GLUT2 in the hepatocytes of chard or/and insulin-treated hyperglycemic rats. The oxidative stress was decreased and antioxidant defense was increased by chard extract or/and insulin treatment to hyperglycemic rats according to the decreased malondialdehyde formation, the activities of catalase, superoxide dismutase, myeloperoxidase and increased glutathione levels. These findings suggest that chard extract might improve glucose response by increasing GLUT2 through Akt2 and antioxidant defense in the liver. (C) 2013 Elsevier GmbH. All rights reserved
Apocynin and dimethyl sulfoxide synergistically protect against ischemia-reperfusion injury in a rat hind limb ischemia-reperfusion model
No full textBackground Acute ischemia and reperfusion in extremities ignite a complicated inflammatory cycle and lead to damage in the extremities and target tissues. Methods Rats were randomly divided into four groups. Each experimental group contained eight rats. Group 1 was the sham surgery group. Group 2 was the control I/R group with intraperitoneal serum physiologic (SP) treatment. Group 3 was the I/R group with vehicle treatment (8% DMSO). Group 4 was the I/R group with 20 mg/kg apocynin (vehicle 8% DMSO). The potential protective effects of apocynin and vehicle (DMSO) in the rat hind limb ischemia-reperfusion model were evaluated by measuring the levels of plasma pro-inflammatory cytokines and oxidative stress markers in muscle tissue. Results The results revealed that both apocynin and vehicle (DMSO) alone increased the antioxidative capacity of ischemic tissue and reduced the levels of plasma proinflammatory cytokines compared to control I/R group. There was a statically more significant effect in the apocynin (vehicle 8% DMSO)-treated group 4. Conclusions We observed that apocynin and DMSO synergistically prevent the I/R injury in rat hind limb ischemia-reperfusion injury model and meaningfully decrease the inflammatory parameters
Tocilizumab's effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer's model
No full textNeuroinflammation plays pivotal roles in the pathogenesis of Alzheimer's disease (AD). IL-6 is pleiotropic cytokine which plays significant pathological role in inflammatory diseases and causes prolonged inflammation. Additionally, IL-6 activates microglia cells and enhances the accumulation of amyloid-beta peptides. Moreover, IL-6 signal transduction is mediated by membrane-bound and soluble IL-6 receptors. Tocilizumab which is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody binds to both of these receptors and inhibits IL-6 signaling by this route. The objective was to investigate tocilizumab's potential effects in the treatment of AD. Male Sprague-Dawley rats were divided into three groups: sham (control), streptozotocin (STZ), and tocilizumab-STZ. We used a single dose of intracerebroventricular (ICV) tocilizumab, beginning 1 h prior to injection of STZ for 3 weeks. The rats in STZ and tocilizumab-STZ groups were given ICV-STZ (3 mg/kg). Behavioral parameters were evaluated on days 17-20 and the rats were sacrificed on day-21 to examine histopathological changes. STZ injection caused significant decrease in the mean escape latency in passive avoidance and also declined the performance improvement in Morris water maze tests. Tocilizumab-STZ group significantly improved learning and spatial memory functions by increasing RLT in the passive avoidance and by shortening escape latency in reaching the platform in the Morris water maze. Histopathological changes were examined using hematoxylin and eosin and immunohistochemical (IHC) stainings. IHC analysis revealed that while protein expressions of amyloid- (3.5 +/- A 0.2) and IL-6 (2.9 +/- A 0.4) showed intense immune-positivity in STZ group, amyloid- (1.3 +/- A 0.1) and IL-6 (1.5 +/- A 0.2) immunoreactivities were substantially decreased in tocilizumab treatment group. We conclude that tocilizumab treatment attenuated significantly STZ-induced cognitive impairment and histopathological changes. Further studies would be desirable to investigate clinically relevant protective effects of tocilizumab in AD
Local Delivery of Chitosan/VEGF siRNA Nanoplexes Reduces Angiogenesis and Growth of Breast Cancer In Vivo
No full textVascular endothelial growth factor (VEGF) is the important angiogenic factor associated with tumor growth and metastasis in a wide variety of solid tumors. The aim of this study is to investigate the tumor suppressive effect of chitosan/small interfering RNA (siRNA)-VEGF nanoplexes in the rat breast cancer model. Chitosan/siRNA nanoplexes (siVEGF-A, siVEGFR-1, siVEGFR-2) and NRP-1 were prepared in a 15 to1 ratio and injected (intratumorally) into the breast-tumor-bearing Sprague-Dawley rats. Tumor volumes were measured during 21 days. To investigate the effect of chitosan/siRNA nanoplexes on VEGF expression in tumors, VEGF was analyzed with immunohistochemistry and western blotting. The mRNA levels of VEGF in tumor samples were determined with real-time PCR (RT-PCR). After siRNA treatment, a marked reduction in tumor volumes was measured in complex-injected rats (97%). Free siRNA injection showed lower tumor inhibition. Reduction of VEGF protein was also shown with western blotting and immunohistochemistry. Similar results were obtained with RT-PCR also. These results indicate that the chitosan/siRNA targeting to VEGF nanoplexes have a remarkably suppressive effect on VEGF expression and tumor volume in breast cancer model of rats
The Effects of Riluzole on Neurological, Brain Biochemical, and Histological Changes in Early and Late Term of Sepsis in Rats
No full textObjective. One of the underlying mechanisms of sepsis is thought to be the oxidative damage due to the generation of free radicals. Glutamate, the major excitatory amino acid in the brain, is known to play an important role in blood brain barrier (BBB) permeability, brain edema, and oxidative damage in pathological conditions. Riluzole, a glutamate release inhibitor, has been shown to have neuroprotective effects in several animal models. The aim of our study was to investigate the putative protective effect of riluzole against sepsis-induced brain injury. Methods. Sepsis was induced by cecal ligation and puncture in Wistar albino rats. Sham operated (control) and sepsis groups received either saline or riluzole (6 mg/kg, s.c.) 30 min after the surgical procedure, and every 12 h as continuing treatment. The effect of riluzole on the survival rate, weight loss, fever, leukocyte count, brain edema, BBB permeability, oxidative damage, and histological observations were evaluated for early (6 h) and late (48 h) phase of sepsis. Results. Riluzole, when administered 6 mg/kg s.c., diminishes the sepsis-induced augmentation in weight loss, body temperature, brain edema, increase in BBB permeability, oxidative damage, and brain injury that is observed histologically. Besides increasing the survival rate in sepsis, it has also improved neurological examination scores and the prognosis of the disease. Conclusion. According to the results of this study, riluzole appears to have a protective effect for sepsis-induced encephalopathy. (C) 2009 Elsevier Inc. All rights reserved
Ischemic colitis of the colon in streptozotocin-induced diabetic rats
No full textThis study focuses on two inflammatory diseases, viz., diabetes mellitus (DM) that causes serious complications such as retinopathy, nephropathy, and neuropathy, and ischemic colitis which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings
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