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1.
Int J Exp Pathol ; 100(5-6): 330-336, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31777145

RESUMEN

One of the most important causes of visual loss (blindness) is glaucoma, which occurs due to the degeneration of the ganglion cells in retina. It has been shown that hydrogen sulphide (H2 S) acts an antioxidant, neuroprotective and neuromodulator and provides protection against oxidative stress and apoptosis. This study aims to examine through which apoptotic pathway H2 S acts in experimental glaucoma model. Twenty-two male wistar albino rats were used in this study. Group 1 (n = 6, control group): Intravitreal saline was given in the third week without inducing ocular hypertension (OHT) with laser photocoagulation. Group 2 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal saline was given in the third week. Group 3 (n = 8): After the induction of OHT with laser photocoagulation, intravitreal H2 S's donor sodium hydrosulphide (NaSH) 100 nmol/L was given in the third week. At the end of the 6th week, the eyes of the rats were sacrified under anaesthesia and extracted and then routine tissue follow-up was undertaken. Besides haematoxylin & eosin (H&E) staining, Bax, Bcl-2, p53 and caspase-3 activation were examined immunohistochemically in the retina and the cornea. This showed that ocular hypertension caused apoptosis through the intrinsic pathway, due to Bax and caspase-3 activation, in both retina and cornea, and that this led to DNA damage due to p53 activation. Also, we found that H2 S exposure in glaucoma distinctly suppressed Bax, caspase-3 and p53 activations in retina but that it has a limited effect on the cornea. According to these results, glaucoma caused apoptosis in the retina through intrinsic pathway, and the damage to the retina could be compensated partially by H2 S but would have limited on the cornea.


Asunto(s)
Apoptosis/efectos de los fármacos , Córnea/diagnóstico por imagen , Glaucoma/tratamiento farmacológico , Sulfuro de Hidrógeno/farmacología , Sustancias Protectoras/farmacología , Retina/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Córnea/metabolismo , Córnea/fisiopatología , Glaucoma/metabolismo , Glaucoma/fisiopatología , Sulfuro de Hidrógeno/administración & dosificación , Sulfuro de Hidrógeno/uso terapéutico , Inyecciones Intravítreas , Masculino , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/uso terapéutico , Ratas , Ratas Wistar , Retina/metabolismo , Retina/fisiopatología
2.
Drug Dev Res ; 77(1): 12-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26748675

RESUMEN

Preclinical Research Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti-inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apoptotic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dimethylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF-α contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evidenced from this study.


Asunto(s)
Antiinflamatorios/administración & dosificación , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Hígado/inmunología , Estilbenos/administración & dosificación , Animales , Antiinflamatorios/farmacología , Apoptosis , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/patología , Eritropoyetina/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Resveratrol , Estilbenos/farmacología , Estreptozocina , Factor de Necrosis Tumoral alfa/metabolismo
3.
J Surg Res ; 199(2): 393-401, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26163327

RESUMEN

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hepatopatías/prevención & control , Hígado/irrigación sanguínea , Daño por Reperfusión/prevención & control , Simvastatina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hígado/enzimología , Hígado/patología , Hepatopatías/patología , Masculino , Distribución Aleatoria , Ratas Sprague-Dawley , Daño por Reperfusión/patología
4.
J Surg Res ; 187(1): 162-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24176208

RESUMEN

PURPOSE: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model. MATERIALS AND METHODS: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses. RESULTS: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL. CONCLUSIONS: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.


Asunto(s)
Iloprost/farmacología , Músculo Esquelético/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Vasodilatadores/farmacología , Animales , Aorta Abdominal , Chaperonina 60/metabolismo , Modelos Animales de Enfermedad , Malondialdehído/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Distribución Aleatoria , Ratas , Daño por Reperfusión/patología , Superóxido Dismutasa/metabolismo
5.
Mol Biol Rep ; 41(10): 6391-5, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25034890

RESUMEN

Laparoscopic surgery techniques have been increasingly preferred to classic laparotomy by surgeons since 1987. However, this method may have some side effects on different intraabdominal organs including kidneys. The aim of this study is to evaluate the effects of different pressures of CO2 on p53 related apoptosis in kidneys. Totally 24 male rats were divided into four equal groups. CO2 is insufflated into rats' intraabdominal cavity in two different pressures of 10 and 20 mmHg during 1 h. However, in sham group, only cannula was inserted, but no gas was insufflated. After 1 h, 30 min reperfusion was applied. At last, the kidneys were excised and p53 expression and apoptosis were evaluated immunohistochemically. All the data revealed that the number of apoptotic cell in kidney' tubular cells significantly increases in proportion to CO2 pressure level. On the other hand, p53 expression was detected only in the highest pressure. Because the low CO2 pressured group' rats had no p53 expression in kidneys, we suggest that this method can be safely used for abdominal surgery. At the same time, increasing in the number of apoptotic cells parallel to pressure also suggest that CO2 pressure level and application time are very important parameters during CO2 pneumoperitoneum.


Asunto(s)
Apoptosis , Riñón/metabolismo , Neumoperitoneo/metabolismo , Neumoperitoneo/fisiopatología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis/genética , Inmunohistoquímica , Riñón/patología , Masculino , Neumoperitoneo/etiología , Ratas , Proteína p53 Supresora de Tumor/genética
6.
Mol Biol Rep ; 40(10): 5733-40, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24057237

RESUMEN

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.


Asunto(s)
FN-kappa B/antagonistas & inhibidores , Sustancias Protectoras/uso terapéutico , Pirrolidinas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Tiocarbamatos/uso terapéutico , Vejiga Urinaria/irrigación sanguínea , Vejiga Urinaria/patología , Animales , Catalasa/metabolismo , Glutatión/metabolismo , Masculino , FN-kappa B/metabolismo , Sustancias Protectoras/farmacología , Pirrolidinas/farmacología , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Tiocarbamatos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Vejiga Urinaria/efectos de los fármacos
7.
Arab J Sci Eng ; 48(1): 1031-1040, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36321067

RESUMEN

Thiophene-containing compounds have antiviral properties and may be among the drugs tested for the treatment of COVID-19 diseases. In order to better understand the molecular definition of the 1-(2´-Thiophen)-2-propen-1-one-3-(2,3,5-trichlorophenyl) molecule from thiophene-containing compounds, the physico-chemical (molecular structure analysis, spectroscopic properties, boundary orbital analysis) mechanisms underlying the protein-ligand interaction should be examined in detail. For this reason, geometric parameters, IR and UV-vis spectra, conformational analysis, electronic, NBO and NLO properties, molecular electrostatic potential map and Mulliken charge distributions of the TTCP molecule were investigated theoretically using DFT theory in the Gaussian program. Accordingly, molecular docking calculations with COVID-19 main protease (PDB 5R7Y) were performed to determine the pharmaceutical activities of the TTCP molecule against coronavirus diseases.

8.
Plant Foods Hum Nutr ; 67(3): 271-6, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22618081

RESUMEN

Fruit skin color, total phenolics, total anthocyanins, soluble solids content, titratable acidity and total antioxidant capacity in fresh fruits of a number of local and well-known fig (Ficus carica L.) genotypes and cultivars grown in northeastern Turkey were determined. TEAC (Trolox equivalent antioxidant capacity) and FRAP (ferric reducing antioxidant power) assays were used to determine total antioxidant capacity. Fruit skin color of genotypes were found to be very diverse, i.e., light green, light purple, purple, dark purple and black. The content of total phenolics, soluble solids content (SSC) and titratable acidity greatly varied in the range from 24 to 237 mg of gallic acid equivalent per 100 g fresh weight, 18.60 to 26.30 % and 0.16 to 0.47 % in local genotypes and studied cultivars. In general, total antioxidant capacities determined by two methods expressed higher values in the local fig genotypes compared with the cultivars. The results suggested that genotype is the main factor that determines difference in the composition of bioactive compounds in figs and provide information on putative health benefits locally grown genotypes.


Asunto(s)
Ácidos/análisis , Antioxidantes/análisis , Color , Ficus/genética , Frutas/química , Genotipo , Fenoles/análisis , Antioxidantes/farmacología , Cromanos/metabolismo , Dieta , Humanos , Solubilidad , Especificidad de la Especie , Turquía
9.
J Surg Res ; 167(1): 113-20, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-20080260

RESUMEN

BACKGROUND: The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1ß, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS: Creatinine, MDA, IL-1ß, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1ß, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION: Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.


Asunto(s)
Abdomen/irrigación sanguínea , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Síndromes Compartimentales/complicaciones , Doxiciclina/uso terapéutico , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Lesión Renal Aguda/metabolismo , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Doxiciclina/farmacología , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Modelos Animales , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/fisiología , Daño por Reperfusión/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo
10.
Brain Inj ; 25(10): 965-71, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21745175

RESUMEN

OBJECTIVES: The aim of this study was to determine whether intravenous immunoglobulin (IVIG) prevents cerebral vasospasm in rabbits with induced subarachnoid haemorrhage (SAH). The effect of IVIG on apoptosis in the endothelial cells of the basilar artery was also evaluated. METHODS: Eighteen New Zealand white rabbits were allocated randomly into three groups. SAH was induced by injecting autologous blood into the cisterna magna. Group 1, the control group, was subjected to sham surgery (no induction of SAH). Group 2 had SAH alone and Group 3 had SAH plus IVIG. Three days after treatment, the animals were sacrificed. The basilar artery tissues were analysed histologically and the malondialdehyde levels in the brain stem tissues were evaluated biochemically. RESULTS: Differences in the histopathological luminal areas and full wall thicknesses in the SAH plus IVIG group and the SAH group were statically insignificant (p > 0.005). The malondialdehyde level was also found to be lower in the IVIG group than in the SAH group, although this difference was not significant (p > 0.005). CONCLUSION: Although the IVIG treatment was revealed to have no vasodilator effect on the SAH-induced spastic basilar artery, it was shown to have a beneficial effect on the apoptosis of endothelial cells, probably via anti-inflammatory mechanisms.


Asunto(s)
Células Endoteliales/patología , Inmunoglobulinas Intravenosas/farmacología , Malondialdehído/metabolismo , Hemorragia Subaracnoidea/complicaciones , Vasodilatadores/farmacología , Vasoespasmo Intracraneal/etiología , Animales , Apoptosis , Arteria Basilar/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunohistoquímica , Masculino , Conejos , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/fisiopatología , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/patología , Vasoespasmo Intracraneal/prevención & control
11.
Cutan Ocul Toxicol ; 30(1): 55-60, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20973756

RESUMEN

BACKGROUND: The results of studies on the effects of retinoids on spermatogenesis are controversial. OBJECTIVES: We evaluated time- and dose-dependent effects of isotretinoin on spermatogenic activity by apoptosis, cyclin D1, E2F, p53 expressions, and Johnsen's scores. METHODS: The rats were divided into three groups. In the 1st group (n = 18), 1 mg/mL/day and in the 2nd group (n = 18) 2 mg/mL/day isotretinoin were administered for 21 days. Flower oil was given to the 3rd (n = 6) control group. On the 7th (groups 1a and 2a), 14th (groups 1b and 2b), and 21st (groups 1c and 2c) days, six rats from the 1st group and six rats from the 2nd group were sacrificed and bilateral orchiectomy was done. RESULTS: The number of cyclin D1 and E2F-positive cells decreased nonsignificantly parallel to days in the 1st group, whereas there was a statistically significant decrease in the 2nd group for the same cells. The p53-positive cells in groups 1c and 2c were increased significantly. CONCLUSIONS: Further studies on the effects of retinoids on spermatogenesis should be conducted. It may be wise to administer contraception to male patients, especially during high-dose and long-term retinoid therapy.


Asunto(s)
Fármacos Dermatológicos/toxicidad , Isotretinoína/toxicidad , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Ciclina D1/metabolismo , Relación Dosis-Respuesta a Droga , Factores de Transcripción E2F/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/patología , Espermatogénesis/fisiología , Testículo/metabolismo , Testículo/patología , Factores de Tiempo , Proteína p53 Supresora de Tumor/metabolismo
12.
J Drugs Dermatol ; 9(10): 1207-10, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20941944

RESUMEN

Wound healing is a complex process, and the role of retinoids in wounds is confusing and controversial. In this study, the authors aimed to evaluate the role of oral isotretinoin on mast cells, collagen production and remodeling in the wound healing process. In the first group 2 mg/kg/day isotretinoin dissolved in sunflower oil were administrated for 28 days. In the second group, only sunflower oil was administered. At the end of first week, four incisions were made on rats' back. In the seventh (group 1a and 2a), fourteenth (group 1b and 2b) and twenty-first (group 1c and 2c) days, the skin biopsies were taken from around of the incision areas from both groups. The authors revealed that isotretinoin administration permanently accelerates mast cell accumulation parallel to days in the wound area. The histological features of wound healing in isotretinoin administered rats were faster and better than the group 2.


Asunto(s)
Fármacos Dermatológicos/farmacología , Isotretinoína/farmacología , Mastocitos/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Colágeno/biosíntesis , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Masculino , Mastocitos/fisiología , Ratas , Ratas Sprague-Dawley
13.
Brain Inj ; 24(6): 877-85, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20433288

RESUMEN

BACKGROUND: The aim of this study was to investigate the ability of levosimendan to prevent cerebral vasospasm in a rabbit model of subarachnoid haemorrhage (SAH). ANIMALS AND METHODS: Eighteen New Zealand white rabbits were allocated into three groups randomly. SAH was induced by injecting autologous blood into the cisterna magna. (Group 1 = control:sham surgery group, Group 2 = SAH alone group, Group 3 = SAH plus levosimendan group). Histopathological examination was performed on day 3 as described. Intravenous levosimendan dose (initially 12 microg kg(-1) infusion, continuously for at least 10 minutes and then continued with a dose of 0.2 microg kg(-1) min(-1)) treatment was started after the induction of SAH. Three days later, the animals were sacrificed. RESULTS: In pathological investigation; there was statistically significant difference in luminal area and muscular wall thickness of the basilar artery between all groups (p < 0.005). Malondialdehyde level was also found significantly low in the levosimendan group compared with the SAH group. CONCLUSION: Intravenous levosimendan treatment was found effective by increasing the pathological luminal area and reducing muscular wall thickness measurements. This is the first study to show that intravenous administration of levosimendan is effective in preventing cerebral vasospasm induced by SAH in rabbits.


Asunto(s)
Hidrazonas/administración & dosificación , Piridazinas/administración & dosificación , Hemorragia Subaracnoidea/complicaciones , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/tratamiento farmacológico , Animales , Arteria Basilar/patología , Infusiones Intravenosas , Masculino , Conejos , Distribución Aleatoria , Simendán , Hemorragia Subaracnoidea/patología , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/patología
14.
Curr Ther Res Clin Exp ; 71(3): 186-98, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24683264

RESUMEN

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and ß-cell lymphoma 2 (ßcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1ß, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of ßcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.

15.
Biol Res ; 42(2): 175-81, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19746262

RESUMEN

Methanolic extracts of eight Salvia species, namely S. aethiopis, S. candidissima, S. limbata, S. microstegia, S. nemorosa, S. pachystachys, S. verticillata, and S. virgata, sampled from Eastern Anatolia in Turkey, were screened for their possible antioxidant activities by two complementary test systems, namely DPPH free radical scavenging and beta-carotene/linoleic acid. Total phenolic content of the extracts of Salvia species were performed Folin-Ciocalteu reagent and gallic acid used as standard. A wide variation has been observed among species in terms of antioxidant activity and total phenolic content. In both DPPH and beta-carotene system, the most active plant was Salvia verticillata with a value of IC50=18.3 microg/ml and 75.8%, respectively. This species also has the highest total phenolic content (167.1 mgGAE/g DW). The total amount of phenolics was between 50.3 to 167.1 mgGAE/g DW among species. A positive linear correlation was observed between total phenolic content and antioxidant activity of the extracts. The results suggest that the extract of Salvia species, notably Salvia verticillata with the highest antioxidant activity, can be used as natural antioxidants in the food industry.


Asunto(s)
Antioxidantes/farmacología , Fenoles/análisis , Extractos Vegetales/farmacología , Salvia/química , Compuestos de Bifenilo , Depuradores de Radicales Libres/farmacología , Picratos , Salvia/clasificación , Turquía , beta Caroteno
16.
Chem Biodivers ; 6(12): 2302-10, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20020464

RESUMEN

The oil obtained by hydrodistillation from the aerial parts of Artemisia incana (L.) Druce from Turkey was analyzed by GC and GC/MS. Sixty-three compounds were characterized, representing 97.2% of the total components detected, and camphor (19.0%), borneol (18.9%), 1,8-cineole (14.5%), bornyl acetate (7.8%), camphene (4.9%), and alpha-thujone (4.8%) were identified as predominant components. The essential oil was also tested for its antimicrobial activity against 44 different foodborne microorganisms, including 26 bacteria, 15 fungi, and 3 yeast species. The essential oil of A. incana exhibited considerable inhibitory effects against all bacteria, fungi, and yeast species tested. However, the oil showed lower inhibitory activity against the tested bacteria than the reference antibiotics.


Asunto(s)
Antiinfecciosos/química , Artemisia/química , Aceites Volátiles/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Cromatografía de Gases , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología
17.
Langenbecks Arch Surg ; 393(6): 877-82, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18057955

RESUMEN

BACKGROUNDS AND AIMS: Laparoscopic surgery techniques have been increasingly preferred to classic laparotomy by surgeons since 1987. However, this method has some important adverse effects on intra-abdominal organs. The aim of this study is to evaluate the effects of different pressures of CO(2) on apoptosis and p53 expression in cells in liver and spleen. METHODS: In total, 30 male Sprague-Dawley rats were used in the study. CO(2) was insufflated into the intra-abdominal cavity via angiocatheter cannule by an insufflator in two different pressures of 10 and 20 mm Hg for 60 min. However, in the control group, only cannule was inserted into the intra-abdominal cavity, but no gas was insufflated. After 60 min, the rats were killed and laparotomy was applied. The liver and spleen were excised. The samples were histologically processed and immunohistochemistry was applied. RESULTS: All the data revealed that the number of apoptotic cells in liver and spleen increases in proportion to CO(2) pressure level. No p53 expression was detected in both organs. CONCLUSION: CO(2) pressure level and application time may affect on cells living in liver and spleen. High pressure and/or long application time may cause releasing of cytokines and superoxide radicals from these organs' cells, and transient or serious organ dysfunctions may occur.


Asunto(s)
Apoptosis/genética , Laparoscopía , Hígado/patología , Neumoperitoneo Artificial , Bazo/patología , Proteína p53 Supresora de Tumor/genética , Presión del Aire , Animales , Expresión Génica/genética , Etiquetado Corte-Fin in Situ , Masculino , Ratas , Ratas Sprague-Dawley
18.
J Laparoendosc Adv Surg Tech A ; 18(3): 365-71, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18503368

RESUMEN

BACKGROUND: Laparoscopic surgical techniques have been increasingly preferred to classic laparotomy by surgeons since 1987. The pneumoperitoneum is often used to facilitate the intra-abdominal field, but it carries the risk of its ischemic potential and has differences [l2]of metabolic, inflammatory, and infectious consequences, depending on the pressure set and kind of gas used. However, the mechanisms related with the cell injury observed after laparoscopy are still unknown. The aim of this study was to evaluate the effects of different pressures of CO(2) on apoptosis and p53 expression in small and large intestines and the stomach. MATERIALS AND METHODS: In total, 30 Sprague-Dawley male rats were used in the study. CO(2) is insufflated into the intra-abdominal cavity through a angiocatheter cannule by an insufflator set at two different pressures of 10 and 20 mm Hg during 60 minutes. In the control group, the cannule was inserted into the intra-abdominal cavity without any other surgical procedure and no gas was insufflated. After 60 minutes, the rats were sacrificed and a laparotomy was performed. The small and large intestines and stomach were excised. The samples were histologically processed and an immunohistochemical analysis was performed. RESULTS: The results of the study revealed that the number of apoptotic cells in intra-abdominal organs we studied increased in proportion to the CO(2) pressure level. However, the p53 expression was detected only in the stomach. CONCLUSIONS: Our study showed that the number of apoptotic cells rises in parallel to the increase in intra-abdominal pressure following the CO(2) pneumoperitoneum in rat large and small intestine and stomach. Although the apoptosis was activated by the p53 pathway in the stomach, it was not so in the large and small intestine.


Asunto(s)
Apoptosis , Dióxido de Carbono/efectos adversos , Genes p53/genética , Intestinos/fisiopatología , Neumoperitoneo Artificial/efectos adversos , Estómago/fisiopatología , Animales , Expresión Génica , Inmunohistoquímica , Masculino , Modelos Animales , Presión/efectos adversos , Ratas , Ratas Sprague-Dawley
19.
Adv Med Sci ; 63(2): 347-352, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30092503

RESUMEN

PURPOSE: Folic acid is an essential vitamin participating in DNA synthesis and repair. Recently folic acid has been shown to stimulate DNA-repair capacity in dermal fibroblasts in response to injury. Thus, the present study aimed to investigate the effects of topical folinic acid, a 5-formyl derivative of tetrahydrofolic acid, on wound healing using rat wound model. MATERIALS AND METHODS: A rat wound model was established, and the wound healing was evaluated by macroscopic and histological analyses among vehicle control, 2.5% folinic acid, 1% folinic acid, and dexpanthenol treatment groups. While an image-analysis program was used to evaluate macroscopic wound closure, connective tissue properties, mast cell numbers, and the expressions of matrix metalloproteinase 1 (MMP-1) and 9 (MMP-9) were evaluated by microscopy. RESULTS: The 2.5% folinic acid-treated group exhibited enhanced wound healing by increased reepithelialization, neo-vessel formation, inflammatory cell migration, collagen deposition and progressive mast cell increase. Furthermore, 2.5% folinic acid induced higher expressions of MMP-1 and MMP-9. CONCLUSIONS: Folinic acid enhances both macroscopic and microscopic wound healing in rat wound model.


Asunto(s)
Leucovorina/administración & dosificación , Leucovorina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Animales , Dermis/patología , Modelos Animales de Enfermedad , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/patología , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas Sprague-Dawley
20.
Drug Des Devel Ther ; 12: 1347-1352, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29861626

RESUMEN

AIM: The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ) on lung injury after myocardial ischemia/reperfusion (I/R). MATERIALS AND METHODS: Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group), left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 µg/kg) (IRL) group, and I/R-thymoquinone (0.2 mL/kg) (IRTQ) group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies. RESULTS: Increased expression of p53 and Bax was observed (4+), especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+). H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to be at an (1+, 2+) intensity that was usually weak and diffuse in multiple areas. Bcl 2 was not found to be expressed in any of the tissues. H&E staining revealed that that the lungs were severely damaged in the I/R group, with the walls of the channels and alveoli thickened and edematous, and also an intense inflammatory cell migration was observed. Immunohistochemical staining was more prominent in inflammatory areas and structures around the terminal bronchioles. CONCLUSION: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ. We suggest that findings of this study be elucidated with further large-scale clinical studies.


Asunto(s)
Benzoquinonas/uso terapéutico , Hidrazonas/uso terapéutico , Lesión Pulmonar/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Piridazinas/uso terapéutico , Animales , Benzoquinonas/administración & dosificación , Hidrazonas/administración & dosificación , Inmunohistoquímica , Inyecciones Intraperitoneales , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Piridazinas/administración & dosificación , Ratas , Ratas Wistar , Simendán , Proteína X Asociada a bcl-2/análisis , Proteína X Asociada a bcl-2/biosíntesis
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