scholarly journals Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy

2016 ◽  
Vol 310 (11) ◽  
pp. R1011-R1019 ◽  
Author(s):  
Manuel Rey-Funes ◽  
Ignacio M. Larrayoz ◽  
Juan C. Fernández ◽  
Daniela S. Contartese ◽  
Federico Rolón ◽  
...  

Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats ( n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue–PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy.

Author(s):  
Juan Carlos Fernández ◽  
Rafael Peláez ◽  
Manuel Rey-Funes ◽  
Manuel Soliño ◽  
Daniela S. Contartese ◽  
...  

2013 ◽  
Vol 91 (10) ◽  
pp. 797-803 ◽  
Author(s):  
Nergiz Hacer Turgut ◽  
Tijen Kaya Temiz ◽  
Bülent Turgut ◽  
Baris Karadas ◽  
Mesut Parlak ◽  
...  

The present study was designed to investigate the effects of YC-1, a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, a NO donor, on smooth muscle responses in the preeclampsia model with suramin-treated rats and on the levels of cyclic guanosine monophosphate (cGMP) of thoracic aorta rings isolated from term-pregnant rats. Rats of 2 groups, control group and suramin group, were given intraperitoneal injection of saline or suramin, respectively. Suramin injection caused increased blood pressure, protein in urine, and fetal growth retardation. Thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction and papaverine relaxation responses were similar. Relaxation responses of YC-1 and DEA/NO decreased in suramin group. In both groups in the presence of ODQ, a sGC inhibitor, the relaxation responses of YC-1 and DEA/NO decreased. The cGMP content was determined by radioimmunoassay technique. The content of cGMP in the suramin group decreased. In the presence of YC-1 and DEA/NO in both groups, cGMP content increased, but in ODQ-added groups, there was a significant decrease. We conclude that in preeclampsia, the decrease of relaxation responses and the decrease of cGMP content could be due to the reduction in stimulation of sGC and the decrease in cGMP levels.


2013 ◽  
Vol 33 (3) ◽  
pp. 230-239 ◽  
Author(s):  
M A Ahbab ◽  
Ü Ündeğer ◽  
N Barlas ◽  
N Başaran

Phthalates are diester derivatives of phthalic acid widely used in many commercial applications. The aim of this study is therefore to evaluate possible genotoxicity of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) at different concentrations using single-cell gel electrophoresis (comet) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assays in testes samples of male rat pups. DCHP and DHP in corn oil were administered to the pregnant rats by gavage at the doses of 0 (vehicle), 20, 100, and 500 mg kg−1 day−1 from gestational day 6 (GD6) to GD19. After delivery, male rats were allowed to grow until prepubertal, pubertal, and adulthood. At necropsy, the blood samples were collected from heart and were excised immediately. The apoptotic cells of prepubertal, pubertal, and adult testis were detected using TUNEL assay. The comet assay was performed on blood lymphocytes and testes samples of adult male rats. The comet assay results showed that tail length, tail intensity, olive tail moment (OTM), and percentage of DNA present in tail were higher when DHP content was increased. Judging from the values of OTM and percentage of DNA, DHP could significantly induce DNA breakage at doses of 100 and 500 mg kg−1 day−1 compared with the control group. An increase in TUNEL-positive cells of prepubertal, pubertal, and adult testicular cells was observed in the treated groups. In conclusion, prenatal exposure to DHP and DCHP may possess genotoxic risk to testicular cells of rats at all stages of development, even at adulthood.


2016 ◽  
Vol 3 (4) ◽  
pp. 563-567
Author(s):  
Семенова ◽  
M. Semenova ◽  
Ковешникова ◽  
E. Koveshnikova

Objective of research: To estimate the effect of new combination drugs Aversect Forte and Aversect Combi on rats. Materials and methods: The present experiment for the evaluation of eventual embyotoxic and teratogenic properties of drugs Aversect Forte and Aversect Combi was conducted on 32 female and 8 male rats based on the current methodological guidelines. Pregnant female rats were divided into 2 experimental and 2 control groups. Drugs were applied between the 7th and the 14th day of pregnancy taking into account the highest sensitivity of embryos towards different types of influence within this time period. Aversect Forte and Aversect Combi were injected to pregnant rats subcutaneously at a dose of 0,3 mg a.i./kg of individual body weight. Rats from the control group received a forming mixture in comparable volume. Within the whole period of pregnancy, we observed the general clinical condition of female rats. Results and discussion: Effects of new domestic preparations Aversect Forte and Aversect Combi on the antenatal development of the rat via subcutaneous injection of preparations to female rats at a dose of 0,3 mg a.i./kg between the 7th and the 14th day of pregnancy were estimated. The test preparations did not cause any external and internal developmental anomalies; indicators of embryo death, mass and dimensions of embryos were at the actual level of control and physiological parameters for that type of animals.


Author(s):  
Rima Benatoui ◽  
Abdelmadjid Bairi ◽  
Abdelkrim Tahraoui

Objective: During the last decade, the role of the β-carboline alkaloid harmine has essentially been studied with regard to its anxiolytic effect, as it was done in our laboratory; therefore, this study has been progressed to cover the effect of this alkaloid on pregnant wistar rats.Methods: The molecule was used at doses of 10 mg/kg, 15 mg/kg, pregnant female rats were divided into three groups according to the stage of pregnancy: first, second, and the third week of pregnancy. Each group has been subdivided into seven subgroups: control group, two treated groups with harmine, acute footshock stress at 1,2mA, sub-acute footshock stress at 0,4mA, psychological stress, and the treated group that footshocked after with 1,2mA, all groups were carried out open field test, plus maze test and light/dark box test.Results: Thigmotaxis is reflected by the significant increase in the traveled distance in peripheral area in the open field of the three groups ‘weeks’ at dose of 10 mg/kg, the enhancement in the number and time of rearing, at both doses, during the second and the last week, the significant increase in the number of entries ‘in open arms’ in plus-maze during the first and third weeks at 15 mg/kg, and the significant decreased in time spent in the light compartment of the light/dark box at the same dose of all groups ‘weeks’ were noticed, which confirm the anxiolytic effect of the alkaloid, even in the case of the footschock stressed pregnant rats of all groups ‘weeks’ that enhancement of number of enties into open arms during the plus maze test.Conclusion: So we can conclude that the anxiolytic effect of harmine not shortening to male rats, but expands to female pregnant wistar rats, and establishes its effect by diminishing time in light compartment of light/dark box and number of entries in open arms of plus maze, in other hand, the increase in the number and the time of rearing reflects the enhancement of exploratory behavior.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.


Author(s):  
Eman A. Al-Rekabi ◽  
Dheyaa K. Alomer ◽  
Rana Talib Al-Muswie ◽  
Khalid G. Al-Fartosi

The present study aimed to investigate the effect of turmeric and ginger on lipid profile of male rats exposed to oxidative stress induced by hydrogen peroxide H2O2 at a concentration of 1% given with consumed drinking water to male rats. Methods: 200 mg/kg from turmeric and ginger were used, and the animals were treatment for 30 days. Results: the results showed a significant increase in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), whereas it explained a significant decrease in high density lipoprotein (HDL) of male rats exposed to oxidative stress when compared with control group. the results showed a significant decrease in cholesterol, triglycerides, (LDL), (VLDL), whereas it explained a significant increase in (HDL) of rats treated with turmeric and ginger at dose 200 mg/kg when compared with male rats exposed to oxidative stress.


Author(s):  
А.В. Солин ◽  
А.Ю. Ляшев ◽  
Ю.Д. Ляшев

Цель исследования - сравнительный анализ влияния селективных агонистов отдельных классов опиоидных рецепторов на белковосинтетическую функцию печени, развитие цитолитического и холестатического синдромов у крыс, подвергшихся частичной гепатэктомии. Методика. Работа выполнена на 152 крысах-самцах Вистар массой 200-250 г. Частичную гепатэктомию выполняли по методу, описанному Higgins G.M. и Anderson R.M. с удалением 70% ткани печени. В плазме крови определяли концентрации общего белка, альбуминов, общего билирубина, активность аланинтрансаминазы (АЛТ), аспартаттрансаминазы (АСТ), лактатдегидрогеназы (ЛДГ) традиционными методами. Опиоиды: DAGO в дозе 6,3 мкг/кг, DSLET в дозе 10,0 мкг/кг, динорфин А (1-13) в дозе 20,1 мкг/кг, вводили внутрибрюшинно ежедневно 1 раз в сутки в течение 5 сут. эксперимента в объеме 0,2 мл. Контрольным животным аналогично вводили физраствор. Результаты. Удаление 70% ткани печени у крыс-самцов Вистар сопровождается развитием печеночной недостаточности, проявляющейся гипербилирубинемией, гипоальбуминемией, гипопротеинемией, повышением активности трансаминаз и лактатдегидрогеназы. Применение селективных агонистов опиоидных рецепторов у крыс, которым моделировали частичную гепатэктомию, оказывало гепатопротективное действие и снижало выраженность проявлений печеночной недостаточности, начиная с 3-х сут. после резекции. Активность трансаминаз, лактатдегидрогеназы и концентрация общего билирубина у животных, которым вводили опиоиды, были существенно ниже, чем в контрольной группе. Содержание общего белка и альбуминов было статистически значимо выше в группах, которые получали исследованные пептиды, по сравнению с контрольной группой на 7-е сут. после частичной гепатэктомии. Наиболее выраженное действие проявлял селективный агонист опиоидных мю-рецепторов DAGO. По нашему мнению, такое влияние пептидов объясняется присущими им антиоксидантным и антигипоксическим эффектами, что снижает повреждающее действие оперативного вмешательства на печень. Более выраженное влияние DAGO связано, по-видимому, с особенностями распределения опиоидных рецепторов или устойчивостью пептида к действию эндопептидаз благодаря модификациям в молекуле пептида. Заключение. Применение опиоидов стимулирует восстановление функциональной активности печени после частичной гепатэктомии. Наибольший эффект отмечается при введении мю-агониста DAGO. Aim. The aim of the study was to compare effects of selective agonists of opioid receptors from different classes on the protein-synthesizing function of liver and development of cytolytic and cholestatic syndromes in rats after partial hepatectomy. Methods. The study was conducted on 152 Wistar male rats weighing 200-250 g. The animals were subjected to partial hepatectomy according to the Higgins and Anderson method. Concentrations of total protein, albumin, total bilirubin, and activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were measured in plasma using standard methods. The opioids, DAGO (6.3 mg/kg), DSLET (10.0 mg/kg), and dynorphin A (1-13) (20.1 mg/kg), were injected in 0.2 ml of saline daily for 5 days. Control animals were injected with 0.2 ml of saline for 5 days. Results. Resection of 70% of liver tissue resulted in development of liver failure as evidenced by hyperbilirubinemia, hypoalbuminemia, hypoproteinemia, and increased transaminase and lactate dehydrogenase activities. Selective agonists of opioid receptors administered to the rats after partial hepatectomy exerted a hepatoprotective effect and alleviated the signs of liver failure beginning from the 3 day after resection. Transaminase and lactate dehydrogenase activities were significantly lower in opioid-treated rats than in the control group. Levels of total protein and albumins were significantly higher in the groups injected with the study peptides compared to the control group on the 7 day after partial hepatectomy. The selective agonist of opioid m-receptors, DAGO, exerted the most pronounced effect. Apparently, the similar effects of peptides were due to their antioxidant and anti-hypoxic action, which alleviated the detrimental effect of liver surgery. The more pronounced effect of DAGO apparently resulted from peculiarities of opioid receptors distribution or peptide resistance to endopeptidase action due to modifications of the peptide molecule. Conclusion. Administration of opioids stimulated restoration of liver functional activity after partial hepatectomy. Injections of the m-agonist, DAGO, produced the most pronounced effect.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


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