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1.
Inflammopharmacology ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504222

RESUMO

AIM: This study aimed to demonstrate the role of serotonin 7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. MATERIAL AND METHOD: Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10 mg/kg as a pre-treatment. One hour after the drug treatments, 25 mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. RESULTS: We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. CONCLUSION: The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

2.
Acta Cir Bras ; 33(7): 609-618, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30110062

RESUMO

PURPOSE: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. METHODS: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. RESULTS: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). CONCLUSIONS: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.


Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Luteolina/farmacologia , Metanol/farmacologia , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Xanthorrhoeaceae/química , Animais , Relação Dose-Resposta a Droga , Glutationa/análise , Glutationa/efeitos dos fármacos , Indometacina , Masculino , Malondialdeído/análise , Ratos Wistar , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Úlcera Gástrica/patologia , Superóxido Dismutase/análise , Superóxido Dismutase/efeitos dos fármacos , Resultado do Tratamento
3.
Acta cir. bras ; 33(7): 609-618, July 2018. graf
Artigo em Inglês | LILACS | ID: biblio-949367

RESUMO

Abstract Purpose: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. Methods: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. Results: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). Conclusions: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.


Assuntos
Animais , Masculino , Úlcera Gástrica/tratamento farmacológico , Extratos Vegetais/farmacologia , Luteolina/farmacologia , Metanol/farmacologia , Xanthorrhoeaceae/química , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Úlcera Gástrica/patologia , Superóxido Dismutase/análise , Superóxido Dismutase/efeitos dos fármacos , Índice de Gravidade de Doença , Indometacina , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Wistar , Relação Dose-Resposta a Droga , Glutationa/análise , Glutationa/efeitos dos fármacos , Malondialdeído/análise
4.
Int Immunopharmacol ; 43: 227-235, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28043031

RESUMO

BACKGROUND AND AIM: Hepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation. METHODS: We therefore examined the biochemical, histopathological and molecular effects of the 5-HT7 receptor agonist and antagonist on inflammatory liver fibrogenesis in animal models of progressive cirrhosis: a mouse model induced by carbon tetrachloride (CCl4) and in Hep3b cells. RESULTS: 5-HT7 expression was observed in the liver in vivo and in vitro in CCl4-induced damage. 5-HT7 receptor agonist but not the antagonist reduced liver markers in mice and in Hep3b cells in carbon tetrachloride (CCl4) induced damage. 5-HT7 agonist, but not antagonist, protected liver tissue from oxidative stress in fibrosis. 5-HT7 agonist but not antagonist induces anti-inflammatory, anti-fibrinotic and anti-cytokine features in liver fibrosis in vivo and in vitro. CONCLUSIONS: 5-HT7 receptors have modulatory function and are an up-and-coming pharmacological target in the inflammatory fibrotic process. 5-HT7 receptor agonist LP-44 showed significant hepatoprotective effects against liver fibrosis, and LP-44 might become a useful therapeutic target for chronic liver inflammation and fibrosis.


Assuntos
Carcinoma Hepatocelular/imunologia , Inflamação , Neoplasias Hepáticas/imunologia , Fígado/metabolismo , Lesão Pulmonar/imunologia , Receptores de Serotonina/metabolismo , Animais , Tetracloreto de Carbono , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular , Fibrose , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Receptores de Serotonina/genética , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Sulfonamidas/farmacologia
5.
Biochem Genet ; 55(1): 34-47, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27586707

RESUMO

This study aimed to investigate the effects of the 5-HT7 receptor agonist (LP44) and antagonist (SB269970) on LPS-induced in vivo tissue damage and cell culture by molecular methods. This study was conducted in two steps. For in vivo studies, 24 female rats were divided into four groups. Group I: healthy; II (2nd h): LPS 5 mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5 mg/kg administered i.p.; IV (8th h): LPS 5 mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2-4 h); II LPS: 1 µg/ml E. Coli O55:B5 strain (2-4 h); III agonist (LP44) 10-9 M (2-4 h); IV antagonist (SB269970) 10-9 M (2-4 h); V LPS+agonist 10-9 M (LP44 1 µg/ml) (2-4 h); VI LPS+antagonist 10-9 M (2-4 h). In molecular analyses, we determined increased TNF-α, IL-1ß, NF-κB, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-α, iNOS, and 5-HT7 mRNA expressions in the A549 cell line. In in vitro parameters, LP44 agonist administration-related decrease was observed. Our study showed that lung 5-HT7 receptor expression is increased in LPS-induced endotoxemia. All this data suggest that 5-HT7 receptor overexpression is an important protective mechanism during LPS-induced sepsis-related cell damage.


Assuntos
Lesão Pulmonar , Receptores de Serotonina/metabolismo , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
6.
Chem Biol Interact ; 258: 266-75, 2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27645307

RESUMO

PURPOSE: Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. METHODS: Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. RESULTS: Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. CONCLUSION: Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.


Assuntos
Amidas/farmacologia , Amidas/uso terapêutico , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Animais , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Indometacina , Cinética , Masculino , Malondialdeído/metabolismo , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/enzimologia , Estômago/patologia , Úlcera Gástrica/genética , Superóxido Dismutase/metabolismo
7.
Peptides ; 82: 35-43, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27208703

RESUMO

This study investigated possible role of U-II and its receptor expression in inflammation by using UTR agonist and antagonist in carrageenan induced acute inflammation. Rats were divided into 5 groups as (1) Healthy control, (2) Carrageenan control, (3) Carrageenan +Indomethacin 20mg/kg, orally, (4) Carrageenan +AC7954 (U-II receptor agonist, intraperitoneally) 30mg/kg and (5) Carrageenan +SB657510 (UTR antagonist, intraperitoneally) 30mg/kg. 1h after drug administration, carrageenan was injected. At the 3rd hour after carrageenan injection, agonist produced no effect while antagonist 63% anti-inflammatory effect respectively. UTR and UT-II expression increased in carrageenan induced paw tissue. Antagonist administration prevented the decrease in an antioxidant system and also capable to decrease TNF-α and IL-6 mRNA expressions. This study showed the role of urotensin II receptors in the physiopathogenesis of acute inflammatory response that underlying many diseases accompanied by inflammation.


Assuntos
Inflamação/tratamento farmacológico , Receptores Acoplados a Proteínas-G/metabolismo , Urotensinas/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina/toxicidade , Cromanos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Indometacina/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/genética , Ratos , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética , Fator de Necrose Tumoral alfa/genética , Urotensinas/genética
8.
Gynecol Endocrinol ; 32(8): 675-683, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26939623

RESUMO

The aim of this study was to evaluate the effects of aliskiren, direct renin inhibitor, as an antioxidant and tissue protective agent and evaluate the molecular, biochemical, and histopathological changes in experimental ischemia and ischemia/reperfusion injury in rat ovaries. Forty-eight female rats were randomly divided into eight groups: in Group 1, only sham operation was performed. Group 2 received 100 mg/kg aliskiren and sham operated. In Group 3, 3 h-period of bilateral ovarian ischemia was applied. Group 4 received a 3-h period of ischemia followed by 3 h of reperfusion. Groups 5 and 6 received 50 and 100 mg/kg, respectively, of aliskiren and bilateral ovarian ischemia was applied (after a 3-h period of ischemia, both ovaries were surgically removed). To Groups 7 and 8, 50 and 100 mg/kg of aliskiren were administered, respectively, and the induction of ischemia was performed. At the end of a 3-h period of ischemia, bilateral vascular clips were removed, and 3 h of reperfusion continued. After the experiments, IL-1ß, IL-6, TNF-α, and iNOS mRNA expressions and SOD, GSH, MDA, renin, and angiotensin-II levels were determined and histopathological changes were examined in rat ovaries. Aliskiren treatment normalized excessive changes in cytokine and oxidative stress markers in both ischemia and ischemia/reperfusion injury. Histopathologically, treatment with aliskiren ameliorated the development of ischemia and/or ischemia/reperfusion tissue injury. This study concluded that aliskiren treatment is effective in reversing ischemia and/or ischemia/reperfusion induced ovary damage via the improvement of oxidative stress, reduction of inflammation, and suppression of the renin-angiotensin aldosterone system.


Assuntos
Amidas/farmacologia , Fumaratos/farmacologia , Isquemia/prevenção & controle , Doenças Ovarianas/prevenção & controle , Substâncias Protetoras/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Amidas/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Fumaratos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Wistar
9.
J Cell Biochem ; 117(3): 638-46, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26280784

RESUMO

Paracetamol is one of the most popular and widely used analgesic and antipyretic agents, but an overdose can cause hepatotoxicity and lead to acute liver failure. Aliskiren directly inhibits renin which downregulates the renin-angiotensin-aldosterone system (RAAS). Recent findings suggest that RAAS system takes part in the pathogenesis of liver fibrosis. We aimed to reveal the relationship between hepatotoxicity and the RAAS by examining paracetamol induced hepatotoxicity. Rats were separated into five groups as follows: control, 100 mg/kg aliskiren (p.o.), 2 g/kg paracetamol (per os (p.o.)), 2 g/kg paracetamol + 50mg/kg aliskiren (p.o.), and 2 g/kg paracetamol + 100 mg/kg aliskiren(p.o.). Samples were analyzed at the biochemical, molecular, and histopathological levels. Paracetamol toxicity increased alanine aminotransferases (ALT), aspartate aminotransferases (AST), renin, and angiotensin II levels in the serum samples. In addition, the SOD activity and glutathione (GSH) levels decreased while Lipid Peroxidation (MDA) levels increased in the livers of the rats treated with paracetamol. Paracetamol toxicity caused a significant increase in TNF-α and TGF-ß. Both aliskiren doses showed an improvement in ALT, AST, oxidative parameters, angiotensin II, and inflammatory cytokines. Only renin levels increased in aliskiren treatment groups due to its pharmacological effect. A histopathological examination of the liver showed that aliskiren administration ameliorated the paracetamol-induced liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the paracetamol group but not in other treatment groups when compared to the control group. In light of these observations, we suggest that the therapeutic administration of aliskiren prevented oxidative stress and cytokine changes and also protected liver tissues during paracetamol toxicity by inhibiting the RAAS.


Assuntos
Acetaminofen/toxicidade , Amidas/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fumaratos/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Alanina Transaminase/sangue , Amidas/uso terapêutico , Angiotensina II/sangue , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Fumaratos/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Oxidantes/metabolismo , Ratos Wistar , Renina/antagonistas & inibidores , Renina/sangue
10.
Inflammation ; 39(1): 336-346, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26412256

RESUMO

This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1ß, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.


Assuntos
Anlodipino/farmacologia , Densidade Óssea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Osteoporose/prevenção & controle , Ovariectomia , Animais , Colágeno Tipo I/biossíntese , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Feminino , Humanos , Hipertensão/tratamento farmacológico , Inflamação/patologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Osteocalcina/metabolismo , Osteopontina/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
11.
Can J Physiol Pharmacol ; 93(4): 269-74, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25730518

RESUMO

High numbers of proinflammatory cells (PMNLs), which are carried by the blood to ischemic tissue during reperfusion, are considered responsible for inducing the inflammatory response that occurs in ischemia-reperfusion (I/R) injury. Our objective was to determine the controlled reperfusion (CR) interval duration (CRID) that would minimize the injury caused by the PMNLs that infiltrate ischemic tissue. Animal groups were divided into the following groups: Sham group, ovarian I/R group (OIR), and ovarian ischemia controlled-reperfusion groups OICR-1, OICR-2, OICR-3, OICR-4, OICR-5, OICR-6, which had their ovarian artery opened and then closed for 10, 8, 6, 4, 2, or 1 s, respectively. The results show that the COX-2 activity and the gene expression decreased while the COX-1 activity and the gene expression were found to be increased in parallel to the shortening of the period in CRID. From the histopathological examinations, the findings of hemorrhage, edema, congested vascular structures, degenerated cells, and migration and adhesion of PMNLs were scaled as follows: Sham group < OICR-6 < OICR-5 < OICR-4 < OICR-3 < OICR-2 < OICR-1. The results from the histopathological assessments were consistent with the molecular and biochemical findings. In conclusion, our findings suggest that increased COX-2 activity plays a role in I/R injury of the rat ovary, and that controlled reperfusion for 3, 2, or 1 s following 2 h of ischemia may attenuate the effects of I/R injury.


Assuntos
Regulação Enzimológica da Expressão Gênica , Infiltração de Neutrófilos , Neutrófilos/imunologia , Ooforite/prevenção & controle , Ovário/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Reperfusão , Animais , Adesão Celular , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Edema/etiologia , Edema/prevenção & controle , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Ooforite/imunologia , Ooforite/metabolismo , Ooforite/patologia , Ovário/imunologia , Ovário/metabolismo , Ovário/patologia , Ratos Wistar , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo
12.
Eurasian J Med ; 47(1): 32-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25745343

RESUMO

OBJECTIVE: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. MATERIALS AND METHODS: The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. RESULTS: Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. CONCLUSION: It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its anti-ulcer effect mechanisms.

13.
Basic Clin Pharmacol Toxicol ; 117(3): 173-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25625309

RESUMO

The aim of this study was to examine the effects of carnitine on bone healing in ovariectomy (OVX) and inflammation (INF)-induced osteoporotic rats. The rats were randomly divided into nine groups (n = 8 animals per group): sham-operated (Group 1: SHAM); sham + magnesium silicate (Mg-silicate) (Group 2: SHAM + INF); ovariectomy (Group 3: OVX); ovariectomy + femoral fracture (Group 4: OVX + FRC); ovariectomy + femoral fracture + Mg-silicate (Group 5: OVX + FRC + INF); ovariectomy + femoral fracture + carnitine 50 mg/kg (Group 6: OVX + FRC + CAR50); ovariectomy + femoral fracture + carnitine 100 mg/kg (Group 7: OVX + FRC + CAR100); ovariectomy + femoral fracture + Mg-silicate + carnitine 50 mg/kg (Group 8: OVX + FRC + INF + CAR50); and ovariectomy + femoral fracture + Mg-silicate + carnitine 100 mg/kg (Group 9: OVX + FRC + INF + CAR100). Eight weeks after OVX, which allowed for osteoporosis to develop, INF was induced with subcutaneous Mg-silicate. On day 80, all of the rats in groups 4-9 underwent fracture operation on the right femur. Bone mineral density (BMD) showed statistically significant improvements in the treatment groups. The serum markers of bone turnover (osteocalcin and osteopontin) and pro-inflammatory cytokines (tumour necrosis factor α, interleukin 1ß and interleukin 6) were decreased in the treatment group. The X-ray images showed significantly increased callus formation and fracture healing in the groups treated with carnitine. The present results show that in a rat model with osteoporosis induced by ovariectomy and Mg-silicate, treatment with carnitine improves the healing of femur fractures.


Assuntos
Carnitina/uso terapêutico , Consolidação da Fratura/efeitos dos fármacos , Inflamação/complicações , Osteoporose/complicações , Absorciometria de Fóton , Animais , Densidade Óssea , Modelos Animais de Doenças , Feminino , Interleucina-1beta/sangue , Interleucina-6/sangue , Osteocalcina/sangue , Osteopontina/sangue , Ovariectomia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
14.
Mater Sci Eng C Mater Biol Appl ; 44: 246-53, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25280703

RESUMO

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.


Assuntos
Boro/química , Ácido Láctico/química , Ácido Poliglicólico/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Absorciometria de Fóton , Animais , Materiais Biocompatíveis/química , Regeneração Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Boro/farmacologia , Calcificação Fisiológica , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Imuno-Histoquímica , Ácido Láctico/farmacologia , Microscopia Eletrônica de Varredura , Osteocalcina/metabolismo , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley
15.
Int Immunopharmacol ; 23(1): 179-85, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25068826

RESUMO

The purpose of this study was to investigate the effect of etoricoxib on oxidative injury induced with ischemia-reperfusion (I/R) in rat kidney tissue in terms of biochemistry and immunohistochemistry. Male Albino Wistar rats were divided into renal I/R (RIR), 50 mg/kg etoricoxib+RIR (ETO-50), 100 mg/kg etoricoxib+RIR (ETO-100) and sham operation (SG) groups. Animals in the ETO-50 and ETO-100 groups were given etoricoxib by the oral route at dosages of 50 and 100 mg/kg, respectively. The RIR and SG groups were given distilled water as solvent. One hour after drug administration, 1h of ischemia and 3h of reperfusion were applied to the left kidneys of all rats (apart from SG) under 25 mg/kg thiopental sodium anesthesia. At the end of that time, kidneys were extracted and biochemical and immunohistochemical analyses were performed. Etoricoxib reduced, in a dose-dependent manner, levels of MDA, MPO and COX-2 that normally rise with I/R in rat kidney tissues. Etorixicob did not alter COX-1 activity at 50 and 100 mg/kg doses, but significantly prevented loss of tGSH in tissues with I/R. In addition, Bcl-2' gene expression inhibited with I/R was prevented in renal tubular and glomerular cells. Furthermore, etoricoxib significantly decreased the caspase-3 gene expression which increased with I/R. Etoricoxib significantly prevented I/R injury in a dose-dependent manner. The results of this study show that etoricoxib treatment could decrease kidney injury during IR.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Rim/efeitos dos fármacos , Piridinas/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Sulfonas/administração & dosagem , Animais , Caspase 3/genética , Caspase 3/metabolismo , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Etoricoxib , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Rim/patologia , Rim/cirurgia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
16.
J Invest Surg ; 26(6): 325-33, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23957729

RESUMO

BACKGROUND: Intestinal ischemia reperfusion (IR) is associated with morbidity and mortality. We first examined the role of levosimendan in the protection of intestine after mesenteric IR. METHODS: The rats were divided into six groups: (1) Control group; (2) Levosimendan group; (3) Ischemia group (60 min of occlusion); (4) IR group (60 min of occlusion and then 60 min reperfusion); (5) IR + 1 mg/kg levosimendan group: Levosimendan was given intraperitonally 30 min prior to the ischemia; (6) IR + 2 mg/kg levosimendan group. RESULTS: The levels of TNF-α, IL-6, and IL-1ß were found to have increased in the IR group. The serum levels of TNF-α, IL-6, and IL-1ß were found to have decreased as a result of the administration of both doses of levosimendan in the IR. Relative TNF-α and NFκB mRNA levels was decreased by administration of both doses of levosimendan in the IR. SOD activity and GSH levels for IR group were lower than, and 8-ISO levels were higher than, those of the sham-operated rat and ischemia alone group. CONCLUSIONS: Both doses of levosimendan had preventive effects on the alterations that occurred in the intestinal tissues after IR. Levosimendan administration attenuated in reperfusion injury of intestine and consequently protects intestinal mucosa and oxidant-antioxidant balance of ileum.


Assuntos
Hidrazonas/uso terapêutico , Intestinos/irrigação sanguínea , Piridazinas/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Interleucina-1beta/sangue , Interleucina-6/sangue , Intestinos/patologia , NF-kappa B/genética , RNA Mensageiro/metabolismo , Ratos , Traumatismo por Reperfusão/patologia , Simendana , Fator de Necrose Tumoral alfa/sangue
17.
Eur J Pharmacol ; 718(1-3): 469-74, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23911880

RESUMO

Osteoporosis is a high mortality and morbidity ranged skeletal disease and results in high costs of medical care in the European Union. We evaluated the possible protective effect of alpha-lipoic acid (ALA) on rat bone metabolism in ovariectomy and inflammation-mediated osteoporosis models. Groups were designed as: (1) sham; (2) sham+inflammation; (3) ovariectomy (OVX); (4) ovariectomy+ALA-25mg/kg; (5) ovariectomy+ALA-50mg/kg; (6) ovariectomy+inflammation; (7) ovariectomy+inflammation+ALA-25mg/kg; and (8) ovariectomy+inflammation+ALA-50mg/kg groups. OVX groups were allowed to recover for two months. Then, inflammation was induced in inflammation groups by subcutaneous talc injection. ALA-25mg/kg and 50mg/kg were administered to drug groups chronically. The skeletal response was assessed by bone mineral density (BMD), osteopontin and osteocalcin measurements. Pro-inflammatory cytokine measurements (interleukin (IL)-1 beta, interleukin-6, and tumor necrosis factor-alpha) were performed to observe inflammatory process. In OVX, INF and OVX+INF groups, BMD levels were lowest and osteocalcin, osteopontin, IL-1 beta, IL-6, and TNF-alpha levels were highest when compared to sham group. ALA administration increased BMD levels and decreased osteocalcin, osteopontin, IL-1 beta, IL-6, and TNF-alpha levels versus OVX and OVX+INF control groups. Both in senile and postmenopausal osteoporosis, the balance in coupling were destroyed on behalf of bone resorption. ALA had a protective effect on both senile and postmenopausal osteoporosis. The positive effect of this drug in these osteoporosis models might originate from its positive effects on bone turnover markers and cytokine levels. From this perspective, ALA may be a candidate for radical osteoporosis treatment both in senile and postmenopausal types clinically at the end of advanced studies.


Assuntos
Fêmur/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ovariectomia/efeitos adversos , Ácido Tióctico/farmacologia , Animais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Fêmur/metabolismo , Fêmur/fisiopatologia , Inflamação/complicações , Osteoporose/complicações , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Ratos , Ratos Wistar , Ácido Tióctico/uso terapêutico
18.
Eur J Pharmacol ; 715(1-3): 270-9, 2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-23742863

RESUMO

The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.


Assuntos
Carragenina/efeitos adversos , Receptores de Serotonina/metabolismo , Animais , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Citocinas/sangue , Edema/sangue , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Membro Posterior/metabolismo , Membro Posterior/patologia , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Serotonina/genética , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia
19.
Immunobiology ; 218(10): 1271-83, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23694713

RESUMO

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.


Assuntos
Pulmão/metabolismo , Receptores de Serotonina/metabolismo , Sepse/imunologia , Animais , Ceco/cirurgia , Citocinas/sangue , Pulmão/patologia , Masculino , Terapia de Alvo Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/administração & dosagem , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Wistar , Receptores de Serotonina/imunologia , Sepse/terapia , Antagonistas da Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/administração & dosagem , Sulfonamidas/administração & dosagem
20.
Int Immunopharmacol ; 16(1): 35-40, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23542012

RESUMO

Sepsis is the systemic response of an organism against microorganisms and toxins. Lithium is a therapeutic agent used for bipolar disorder and neurodegenerative disease, and it exerts pleiotropic effects on various cellular processes. The present study aimed to determine the effect of lithium on cecal ligation and puncture (CLP)-induced tissue injury in the lungs, by inhibiting the pro-inflammatory cytokine response, and the generation of reactive oxygen species (ROS) triggered by polymicrobial sepsis. Five groups of 20 rats each were used: 1) sham-operated control group; 2) CLP group; 3) 50mg/kg lithium-treated control healthy group; 4) 25 mg/kg lithium-treated CLP group; and 5) 50 mg/kg lithium-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All rat groups were killed 16 h later, and lung and blood samples were analyzed histopathologically and biochemically. The 25 and 50 mg/kg of lithium decreased the level of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and the tumor necrosis factor-α (TNF-α) in the serum, and the 8-iso-prostaglandin F2α (8-ISO) level in lung tissue. The lithium also increased the activity of superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung tissues of rats. The histopathological scores and examinations were in accordance with the biochemical results, and revealed significant differences in the inflammation scores between the sepsis group and the other groups. The CLP+lithium 50mg/kg group had the lowest inflammation score among the CLP groups. Our results indicated that the therapeutic administration of lithium prevented oxidative stress changes and cytokine changes, and also protected vital tissues.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Carbonato de Lítio/uso terapêutico , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/sangue , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Carbonato de Lítio/farmacologia , Masculino , Ratos , Ratos Wistar , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/metabolismo
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