RESUMO
ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Assuntos
Animais , Masculino , Ratos , Pirazinas/uso terapêutico , Obstrução Ureteral/complicações , Fator 2 Relacionado a NF-E2/uso terapêutico , Nefropatias/tratamento farmacológico , Tionas , Tiofenos , Obstrução Ureteral/patologia , Obstrução Ureteral/tratamento farmacológico , Fibrose/etiologia , Fibrose/tratamento farmacológico , Imuno-Histoquímica , Caderinas/sangue , Ratos Wistar , Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/sangue , Hidroxiprolina/sangue , Nefropatias/etiologia , Nefropatias/patologia , Óxido Nítrico/sangueRESUMO
ABSTRACT Objectives: To evaluate protective effects of darbepoetin and tadalafil against ischemia-reperfusion injury in ipsilateral and contralateral testicle. Materials and Methods: Thirty 3-month-old adult male Wistar-Albino rats were randomly divided into 5 groups (A-E). Sham operation was performed in the first group. In Group B, rats did not received any medication after creating 720 degrees torsion of the left testis. The rats in Group C, D and E received darbepoetin, tadalafil, and darbepoetin/tadalafil combination 30 minutes after creating 720 degrees torsion of the left testis, respectively. The testes of rats in these three groups were detorsioned at 90 minutes after drug administration. Both testes were removed at 30 minutes after detorsion. Results: There were significant differences between the groups in terms of the degree of histopathological damage, Johnsen score, fibrosis score and caspase-3 immunoreactivity in the torsioned testes (p: 0.000). The results for each parameter in the left testes were significantly better in the darbepoetin / tadalafil combination group. Similarly, there were also significant differences in the contralateral testes (p: 0.000). Conclusion: The active substances darbepoetin and tadalafil that were used as a combination had protective effects on both testes and produced out better results in preserving testicular histology. Especially in cases where it is not possible to rescue the torsioned testis, this result was more noticeable in the contralateral testis.
Assuntos
Animais , Masculino , Ratos , Torção do Cordão Espermático/tratamento farmacológico , Vasodilatadores/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Tadalafila/administração & dosagem , Darbepoetina alfa/administração & dosagem , Torção do Cordão Espermático/patologia , Xilazina/administração & dosagem , Imuno-Histoquímica , Distribuição Aleatória , Ratos Wistar , Modelos Animais de Doenças , Ketamina/administração & dosagemRESUMO
OBJECTIVES: To evaluate protective effects of darbepoetin and tadalafil against ischemiareperfusion injury in ipsilateral and contralateral testicle. MATERIALS AND METHODS: Thirty 3-month-old adult male Wistar-Albino rats were randomly divided into 5 groups (A-E). Sham operation was performed in the first group. In Group B, rats did not received any medication after creating 720 degrees torsion of the left testis. The rats in Group C, D and E received darbepoetin, tadalafil, and darbepoetin/ tadalafil combination 30 minutes after creating 720 degrees torsion of the left testis, respectively. The testes of rats in these three groups were detorsioned at 90 minutes after drug administration. Both testes were removed at 30 minutes after detorsion. RESULTS: There were significant differences between the groups in terms of the degree of histopathological damage, Johnsen score, fibrosis score and caspase-3 immunoreactivity in the torsioned testes (p: 0.000). The results for each parameter in the left testes were significantly better in the darbepoetin / tadalafil combination group. Similarly, there were also significant differences in the contralateral testes (p: 0.000). CONCLUSION: The active substances darbepoetin and tadalafil that were used as a combination had protective effects on both testes and produced out better results in preserving testicular histology. Especially in cases where it is not possible to rescue the torsioned testis, this result was more noticeable in the contralateral testis.
Assuntos
Darbepoetina alfa/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Torção do Cordão Espermático/tratamento farmacológico , Tadalafila/administração & dosagem , Vasodilatadores/administração & dosagem , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Ketamina/administração & dosagem , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Torção do Cordão Espermático/patologia , Xilazina/administração & dosagemRESUMO
INTRODUCTION: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. MATERIALS AND METHODS: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-ß1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. RESULTS: TGF-ß1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. CONCLUSIONS: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.
Assuntos
Nefropatias/tratamento farmacológico , Fator 2 Relacionado a NF-E2/uso terapêutico , Pirazinas/uso terapêutico , Obstrução Ureteral/complicações , Animais , Caderinas/sangue , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Fibrose/etiologia , Hidroxiprolina/sangue , Imuno-Histoquímica , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Tionas , Tiofenos , Fator de Crescimento Transformador beta1/sangue , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/patologiaRESUMO
Introduction/Objective: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. Materials and Methods: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56μmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). Conclusions: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.
Assuntos
Animais , Masculino , Anti-Inflamatórios/farmacologia , Sulfeto de Hidrogênio/farmacologia , Insuficiência Renal/prevenção & controle , Obstrução Ureteral/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Creatinina/sangue , Modelos Animais de Doenças , Fibrose , Glutationa/análise , Sulfeto de Hidrogênio/uso terapêutico , Rim/patologia , Malondialdeído/análise , Óxido Nítrico/análise , Estresse Oxidativo , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Fatores de Tempo , Ureia/sangue , Obstrução Ureteral/complicaçõesRESUMO
INTRODUCTION: Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. MATERIALS AND METHODS: 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). RESULTS: There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005). CONCLUSION: We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.
Assuntos
Acetatos/uso terapêutico , Cisteína/antagonistas & inibidores , Rim/efeitos dos fármacos , Antagonistas de Leucotrienos/uso terapêutico , Quinolinas/uso terapêutico , Insuficiência Renal/prevenção & controle , Obstrução Ureteral/complicações , Acetatos/farmacologia , Animais , Creatinina/sangue , Ciclopropanos , Fibrose/prevenção & controle , Glutationa/análise , Rim/patologia , Antagonistas de Leucotrienos/farmacologia , Leucotrienos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Óxido Nítrico/análise , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Quinolinas/farmacologia , Ratos Wistar , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/patologia , Reprodutibilidade dos Testes , Sulfetos , Resultado do Tratamento , Ureia/sangueRESUMO
Introductıon Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. Mateirıals and Methods 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005). Conclusıon We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO. .
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/química , Carcinoma Ductal de Mama/química , Proteínas de Ligação a DNA/análise , Transição Epitelial-Mesenquimal , Receptor alfa de Estrogênio/análise , Fatores de Transcrição/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Caderinas/análise , Carcinoma Ductal de Mama/patologia , Imuno-Histoquímica , Valor Preditivo dos Testes , Prognóstico , Análise Serial de Tecidos , beta Catenina/análiseRESUMO
INTRODUCTION/OBJECTIVE: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. MATERIALS AND METHODS: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56 µmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). RESULTS: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). CONCLUSIONS: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.