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1.
Phytomedicine ; 55: 191-199, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668429

RESUMO

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-α and IL-1ß 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-α, IL-1ß 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.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Alcaloides de Veratrum/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/metabolismo , Carragenina/toxicidade , Avaliação Pré-Clínica de Medicamentos/métodos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Enzimas/metabolismo , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Ratos Sprague-Dawley , Rizoma/química , Fator de Necrose Tumoral alfa/metabolismo , Veratrum/química , Alcaloides de Veratrum/administração & dosagem , Alcaloides de Veratrum/isolamento & purificação
2.
J Cell Biochem ; 117(2): 308-19, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25941092

RESUMO

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.


Assuntos
Acetilcisteína/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Úlcera Gástrica/tratamento farmacológico , Acetilcisteína/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carragenina , Catalase/metabolismo , Avaliação Pré-Clínica de Medicamentos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Glutationa Transferase/metabolismo , Indometacina , Peroxidação de Lipídeos , Estresse Oxidativo , Peroxidase/metabolismo , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/enzimologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Superóxido Dismutase/metabolismo
3.
Chem Biodivers ; 12(11): 1756-67, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26567953

RESUMO

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.


Assuntos
Álcoois/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Indometacina/farmacologia , Líquens/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Álcoois/química , Álcoois/isolamento & purificação , Álcoois/metabolismo , Animais , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Líquens/química , Peroxidação de Lipídeos/efeitos dos fármacos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Úlcera Gástrica/metabolismo
4.
J Food Sci ; 77(11): H224-30, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23057764

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Indometacina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Estômago/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Glutationa/análise , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Estômago/patologia , Superóxido Dismutase/metabolismo
5.
Mediators Inflamm ; 2012: 438912, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22665951

RESUMO

The possible role of ß-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the ß-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 ß-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 ß-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 ß-2 adrenergic receptors in inflammatory and hyperalgesic conditions.


Assuntos
Albuterol/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Carragenina/toxicidade , Edema/tratamento farmacológico , Edema/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/tratamento farmacológico , Animais , Edema/induzido quimicamente , Glutationa/metabolismo , Hiperalgesia/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
6.
Eur J Pharmacol ; 674(2-3): 171-8, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22119377

RESUMO

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.


Assuntos
Anisóis/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Óleos Vegetais/farmacologia , Próteses e Implantes/efeitos adversos , Titânio/efeitos adversos , Animais , Caspases/metabolismo , Contagem de Células , Glutationa/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Azeite de Oliva , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Coelhos , Superóxido Dismutase/metabolismo
7.
Cardiology ; 119(4): 235-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22041688

RESUMO

OBJECTIVES: Menopause has a negative effect on cardiovascular functions. However, very little is known of the overall effect of menopause on the cardiac ultrastructure or the pathophysiological basis of this. METHODS: A group of 12-week-old female Sprague Dawley rats were randomly allocated to healthy control (n = 6) and ovariectomy groups (n = 6). Twelve weeks after ovariectomy, the rats' cardiac tissues were histopathologically analyzed for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of glutathione (GSH) and lipid peroxidation (LPO)]. RESULTS: When compared to the control group, the ovariectomy group showed cardiomyopathic changes. In tissue, activities of CAT (185 ± 2.4 vs. 112 ± 1.4 mmol/min/mg tissue; p < 0.05), SOD (153 ± 1.0 vs. 146 ± 0.7 mmol/min/mg tissue; p < 0.05) and MPO (19 ± 0.8 vs. 8.6 ± 0.11 µmol/min/mg tissue; p < 0.05) and LPO levels (32.1 ± 0.77 vs. 14.4 ± 0.20 nmol/g tissue; p < 0.05) were significantly increased in the ovariectomy group when compared to the control group. However, GSH levels (3.43 ± 0.02 vs. 3.73 ± 0.01 nmol/g tissue; p < 0.05) were significantly lower in the ovariectomy group when compared to the control group. CONCLUSION: Using an experimental animal model, we were able to demonstrate that menopause causes cardiomyopathic changes, and we propose that these changes could be mediated by oxidative stress.


Assuntos
Cardiomiopatias/etiologia , Menopausa/fisiologia , Estresse Oxidativo/fisiologia , Animais , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Catalase/metabolismo , Feminino , Glutationa/metabolismo , Peroxidação de Lipídeos/fisiologia , Miocárdio/enzimologia , Miocárdio/patologia , Ovariectomia , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
8.
J Invest Surg ; 24(6): 283-91, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22047201

RESUMO

ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone-treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries.


Assuntos
Enteropatias/prevenção & controle , Intestinos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Testosterona/farmacologia , Animais , Masculino , Orquiectomia , Estresse Oxidativo/efeitos dos fármacos , Ratos
9.
ScientificWorldJournal ; 11: 1341-56, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21789470

RESUMO

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.


Assuntos
Acetatos/farmacologia , Ceco/lesões , Citocinas/metabolismo , Substâncias Protetoras/farmacologia , Quinolinas/farmacologia , Animais , Modelos Animais de Doenças , Glutationa/metabolismo , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Peróxidos Lipídicos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/prevenção & controle , Miocárdio/metabolismo , Miocárdio/patologia , Peroxidase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sepse/metabolismo , Sepse/mortalidade , Sepse/patologia , Superóxido Dismutase/metabolismo
10.
Pharmacol Rep ; 63(2): 518-26, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21602607

RESUMO

A gastroprotective effect occurs when α(2) receptors are innervated. The dextro isomer of medetomidine, dexmedetomidine, is a highly selective α(2)-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 mm(2), respectively, the ulcerous area was 52.1 ± 4.5 mm(2) in the indomethacin control group and 0.5 ± 0.2 mm(2) in the famotidine group. In conclusion, the α(2)-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 α(2)-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.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Indometacina/toxicidade , Úlcera Gástrica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Antioxidantes/metabolismo , Dexmedetomidina/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Famotidina/farmacologia , Masculino , Oxidantes/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
11.
Eur J Obstet Gynecol Reprod Biol ; 157(1): 94-100, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21439711

RESUMO

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 3h 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 3h of reperfusion continued. Group 7 received a sham operation plus 2mg/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, stromal 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.


Assuntos
Antioxidantes/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Ovário/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Edema/prevenção & controle , Feminino , Glutationa/metabolismo , Hemorragia/prevenção & controle , Hormônio do Crescimento Humano/administração & dosagem , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Isquemia/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ativação de Neutrófilo/efeitos dos fármacos , Ovário/irrigação sanguínea , Ovário/metabolismo , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo , Torção Mecânica
12.
Br J Nutr ; 105(1): 31-43, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21073761

RESUMO

α-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily absorbed and bioavailable compound capable of scavenging a number of free radicals, and it has been used for treating diseases in which oxidative stress plays a major role. The present study was designed to gain a better understanding for the positive effects of ALA on the models of acute and chronic inflammation in rats, and also determine its anti-oxidative potency. In an acute model, three doses of ALA (50, 100 and 200 mg/kg) and one dose of indomethacin (25 mg/kg) or diclofenac (25 mg/kg) were administered to rats by oral administration. The paw volumes of the animals were calculated plethysmometrically, and 0·1 ml of 1 % carrageenan (CAR) was injected into the hind paw of each animal 1 h after oral drug administration. The change in paw volume was detected as five replicates every 60 min by plethysmometry. In particular, we investigated the activities of catalase, superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited anti-inflammatory effects on both acute and chronic inflammations, and a strongly anti-oxidative potency on linoleic acid oxidation. Moreover, the administration of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity, (3) the increases of GST and iNOS activities and the amount of LPO and (4) the decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion, these results suggest that the anti-inflammatory properties of ALA, which has a strong anti-oxidative potency, could be related to its positive effects on the antioxidant system in a variety of tissues in rats.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Edema/prevenção & controle , Enzimas/metabolismo , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Ácido Tióctico/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Carragenina , Fibra de Algodão , Modelos Animais de Doenças , Edema/induzido quimicamente , Membro Posterior , Inflamação/induzido quimicamente , Inflamação/metabolismo , Ácido Linoleico/metabolismo , Masculino , Ratos , Ratos Wistar , Ácido Tióctico/farmacologia
13.
Fertil Steril ; 95(4): 1360-6, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20850724

RESUMO

OBJECTIVE: To reveal the effects of montelukast as an antioxidant and tissue protective agent and study the biochemical and histopathologic changes in experimental ischemia and ischemia-reperfusion (I/R) injury in rat ovaries. DESIGN: Experimental study. SETTING: Experimental surgery laboratory in a university department. ANIMAL(S): Forty-eight rats with experimentally induced ovarian torsion. INTERVENTION(S): Group 1: sham; Group 2: ovarian ischemia; Group 3: a 30-hour period of ischemia followed by a 3-hour reperfusion. Groups 4 and 5: rats administered 10 and 20 mg/kg doses of montelukast before a half-hour of ischemia, then ovarian ischemia applied; after a 3-hour period of ischemia, the bilateral ovaries removed. Groups 6 and 7: 3-hour period of ovarian ischemia applied, then 2.5 hours after the ischemia induction, rats given montelukast. Group 8: sham operation and 20 mg/kg of montelukast; at the end of a 3-hour period of ischemia, 3-hours of reperfusion continued. MAIN OUTCOME MEASURE(S): Measurement of ovarian tissue concentrations of superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and myeloperoxidase (MPO) activity; and histopathologic examination of all ovarian rat tissue. RESULT(S): Montelukast treatment normalized changes of LPO and MPO and stimulated an overproduction of endogenous SOD and GSH. The results of the histologic parameters showed that treatment with montelukast in the I/R group of rats ameliorated the development of ischemia and reperfusion tissue injury. CONCLUSION(S): Montelukast at different doses attenuates ovarian I/R-induced ovary tissue injury in rats.


Assuntos
Acetatos/uso terapêutico , Doenças Ovarianas/patologia , Doenças Ovarianas/prevenção & controle , Substâncias Protetoras/uso terapêutico , Quinolinas/uso terapêutico , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Acetatos/farmacologia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Feminino , Doenças Ovarianas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia , Quinolinas/farmacologia , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo
14.
J Surg Res ; 169(1): 67-75, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20080253

RESUMO

BACKGROUND: The rat sepsis model in the present study was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or together, on the response of pro-inflammatory mediators and oxidative response. MATERIALS AND METHODS: Polymicrobial sepsis was induced using cecal ligation and two-hole puncture. Diabetes was induced in the female Wistar albino rats using intraperitoneal administration of aqueous alloxan monohydrate at a single dose of 150 mg/kg body weight. The rats were divided into five groups: sham control: group 1, ovariectomy: group 2, ovariectomy + sepsis: group 3, ovariectomy + diabetes: group 4, and ovariectomy + diabetes + sepsis: group 5. RESULTS: In lung, heart, and liver tissues, the levels of myeloperoxidase (MPO) and lipid peroxidation (LPO) were higher for the groups 3, 4, and 5 than in control group. In heart and liver tissues, superoxide dismutase (SOD) and catalase (CAT) activities were higher for the groups 3, 4, and 5 than control group. In lung tissue SOD activities were higher for the groups 3, 4, and 5 than in control group. Diabetes + ovariectomy caused a significant increase in serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in comparison to the sham group. The strongest production of TNF-α and IL-6 in serum was observed in the group 5. CONCLUSIONS: Hyperglycemia and ovariectomy (postmenopausal period) severely increased serum cytokines and oxidant levels with the stages of our sepsis model. The lung tissue was most affected by diabetes and ovariectomy under sepsis conditions. Ovariectomy leading to estrogen deficiency results in general changes in metabolism, which are seen in the liver, lungs, and heart with diabetes under sepsis conditions.


Assuntos
Antioxidantes/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Ovariectomia , Sepse/metabolismo , Aloxano , Animais , Catalase/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Feminino , Hiperglicemia/metabolismo , Peroxidação de Lipídeos/fisiologia , Peroxidase/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue
15.
J Pharm Pharmacol ; 62(1): 85-90, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20723003

RESUMO

OBJECTIVES: Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. METHODS: We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. KEY FINDINGS: Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. CONCLUSIONS: These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione.


Assuntos
Antiulcerosos/farmacologia , Eritropoetina/farmacologia , Famotidina/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/administração & dosagem , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Eritropoetina/administração & dosagem , Famotidina/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Glutationa/metabolismo , Indometacina/toxicidade , Masculino , Oxidantes/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
16.
Ren Fail ; 32(5): 592-602, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20486843

RESUMO

OBJECTIVES: Sepsis model was used to understand the role of sustained hyperglycemia and ovariectomy, either separately or concomitantly, on the response of the activity of the nuclear factor kappa B (NF-kappaB) and the oxidative response in kidney. SUBJECTS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Diabetes was induced in female rats using administration of alloxan. The rats were divided into five groups: sham control (group 1), ovariectomy (group 2), ovariectomy + sepsis (group 3), ovariectomy + diabetes (group 4), and ovariectomy + diabetic + sepsis (group 5). RESULTS: In kidney tissues, the levels of lipid peroxidation (LPO) and glutathione (GSH) and the activity of catalase (CAT) were higher for groups 3, 4, 5 than the control groups. Superoxide dismutase (SOD) activity was lower for groups 3, 4, 5 than the control groups. We determined that CLP produced injury evident in the kidneys of rats when compared to the control group, whereas the severity of the injury was higher in the diabetes + ovariectomy + CLP group when compared to the CLP group. In immunohistochemical staining, we determined that CLP operation increased NF-kappaB activation. In the ovariectomized, septic, and diabetic group, NF-kappaB activation was significantly higher than other groups. CONCLUSIONS: Hyperglycemia and ovariectomy severely increased NF-kappaB activation and oxidant levels with the stages of our sepsis model. Ovariectomy resulted in general changes in metabolism, which are seen in the kidney with diabetes under sepsis conditions.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Sepse/metabolismo , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Peso Corporal , Creatinina/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Feminino , Imuno-Histoquímica , Rim/patologia , Ovariectomia , Ratos , Ratos Wistar , Sepse/complicações , Sepse/patologia
17.
Naunyn Schmiedebergs Arch Pharmacol ; 381(5): 455-66, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20349047

RESUMO

The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group II, a sham operation +10 mg/kg atorvastatin; group III, bilateral ovarian ischemia; and groups IV and V, bilateral ovarian ischemia +5 and 10 mg/kg atorvastatin before 30 min of ischemia, respectively (after a 3-h period of ischemia, the bilateral ovaries were surgically removed); group VI, 3-h period of ischemia followed by 3-h reperfusion; groups VII and VIII received 5 and 10 mg/kg atorvastatin, respectively, 2.5 h after the induction of ischemia, and at the end of a 3-h period of ischemia, bilateral vascular clips were removed and 3-h reperfusion continued. After the experiments, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity and levels of glutathione (GSH) and lipid peroxidation (LPO) were determined, and histopathological changes were examined in all rat ovarian tissue. Ischemia and I/R increased the LPO level and MPO activity while decreasing the SOD activity and GSH level significantly in comparison to the sham group. The 5- and 10-mg/kg doses of atorvastatin before ischemia and I/R reversed the trend in LPO level and MPO activity. The levels of SOD and GSH were decreased by ischemia and I/R. The administration of atorvastatin before ischemia and I/R treatments also reversed the trend in the SOD and GSH levels. In the I/R plus atorvastatin groups, although minimal vascular dilation in the ovary stoma and some degenerative cell clusters were seen, most of the cellular structures showed no pathological changes. Administration of atorvastatin is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.


Assuntos
Antioxidantes/farmacologia , Ácidos Heptanoicos/farmacologia , Ovário/efeitos dos fármacos , Pirróis/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/administração & dosagem , Atorvastatina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Ácidos Heptanoicos/administração & dosagem , Isquemia/tratamento farmacológico , Isquemia/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ovário/patologia , Peroxidase/efeitos dos fármacos , Peroxidase/metabolismo , Pirróis/administração & dosagem , Ratos , Ratos Wistar , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo
18.
Shock ; 33(5): 479-84, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19823117

RESUMO

One of the common lethal complications of septic shock, a major cause of morbidity and mortality in patients with severe trauma and so on, is acute lung injury. alpha-Lipoic acid (ALA), with antioxidant properties, is a popular agent. Thus, we investigated the potential protective effects of ALA (200 mg/kg) on sepsis-induced acute lung injury. Rats were exposed to cecal ligation and puncture (CLP) to induce sepsis. Rat groups were designed as (a) sham operated, (b) sham operated + ALA treated, (c) CLP applied, (d) CLP + ALA treated. Sixteen hours after CLP induction, serum samples and lung tissues were obtained for biochemical and histopathological examination. alpha-Lipoic acid decreased the serum levels of inflammatory cytokines such as TNF-alpha and IL-6, which increased after CLP. Increased activity of nuclear factor kappaB in septic lung tissues was decreased by ALA. alpha-Lipoic acid improved the decreased antioxidant activity and alleviated the increased oxidant activity, which occurred after CLP application. We can suggest that ALA showed beneficial effects by decreasing nuclear factor kappaB activation in lung tissues, resulting in decreased serum levels of TNF-alpha and IL-6, and also increasing the antioxidant capacity of the lungs.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , NF-kappa B/metabolismo , Sepse/complicações , Ácido Tióctico/uso terapêutico , Lesão Pulmonar Aguda/fisiopatologia , Animais , Ceco/lesões , Ceco/patologia , Modelos Animais de Doenças , Interleucina-6/sangue , Ligadura/efeitos adversos , Masculino , Punções/efeitos adversos , Ratos , Ratos Wistar , Sepse/tratamento farmacológico , Sepse/mortalidade , Fator de Necrose Tumoral alfa/sangue
19.
Fertil Steril ; 93(4): 1299-307, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19200977

RESUMO

OBJECTIVE: To evaluate the effects of telmisartan as an antioxidant and for its tissue protective properties and to study the biochemical and histopathologic changes in experimental ischemia and ischemia/reperfusion injuries in rat ovaries. DESIGN: Experimental study. SETTING: Experimental surgery laboratory in a university department. ANIMAL(S): Forty-eight female adult rats. INTERVENTION(S): I: sham operation; II: bilateral ovarian ischemia; III: 3 h ischemia + 3 h reperfusion. IV and V: Rats were administered 10 and 20 mg/kg doses of telmisartan, respectively, before 0.5 h of ischemia, and then ovarian ischemia was applied; after 3 h of ischemia, the ovaries were removed. VI and VII: 3 h ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of telmisartan; at the end of 3 h of ischemia, the ovaries were removed and a 3 h reperfusion followed. MAIN OUTCOME MEASURE(S): Superoxide dismutase, inducible nitric oxide synthase, and myeloperoxidase activity in rat ovarian tissue; and histopathologic changes in the ovarian tissue of the rats. RESULT(S): Ischemia and ischemia-reperfusion increased the inducible nitric oxide synthase and myeloperoxidase activity while decreasing the super oxide dismutase activity significantly in comparison with the sham group. Before ischemia and ischemia/reperfusion, telmisartan reversed the trend in inducible nitric oxide synthase activities and the level of myeloperoxidase. CONCLUSION(S): telmisartan is effective in reversing tissue damage induced by ischemia/reperfusion in ovaries.


Assuntos
Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Ovário/irrigação sanguínea , Ovário/patologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Feminino , Óxido Nítrico Sintase Tipo II/metabolismo , Ovário/metabolismo , Ovário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peroxidase/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Superóxido Dismutase/metabolismo , Telmisartan
20.
J Nat Med ; 64(1): 42-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19830512

RESUMO

The anti-inflammatory effects of the methanol extract of the lichen species Peltigera rufescens (Weis.) Humb (MEPR) (Peltigeraceae) on acute (carrageenan-induced) and chronic (cotton pellet granule) phases of inflammation were investigated. The MEPR was capable of reducing carrageenan-induced inflammation and showed a potent antiproliferative effect (63.5%) in the chronic inflammation model. Inflammation is related to neutrophil infiltration and the production of neutrophil-derived mediators and free radicals. The MEPR reduced the myeloperoxidase and inducible nitric oxide synthase (NOS) activities, which were increased by carrageenan injection. Carrageenan injection also increased the lipid peroxidation (LPO) as compared with untreated paw tissues. The administration of MEPR, diclofenac, and indomethacin reduced the LPO in paw tissues through amelioration of the antioxidant defense systems. Neutrophil infiltration and neutrophil-derived free radicals in tissues therefore appeared to play an important role in the inflammation process induced by carrageenan. The anti-inflammatory effect of MEPR could be attributed to its reducing effect on the neutrophil-derived free radicals and its ameliorating effect on the antioxidant defense systems.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Líquens/química , Extratos Vegetais/farmacologia , Doença Aguda , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Carragenina , Doença Crônica , Diclofenaco/farmacologia , Modelos Animais de Doenças , Indometacina/farmacologia , Inflamação/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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