RESUMO
PURPOSE: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. MATERIALS AND METHODS: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. RESULTS: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCL(p<0.001), carbachol(p<0.01), electrical field stimulation(p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine ß-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. CONCLUSIONS: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.
Assuntos
Sulfeto de Hidrogênio , Obstrução do Colo da Bexiga Urinária , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Trifosfato de Adenosina/uso terapêutico , Animais , Carbacol/metabolismo , Carbacol/farmacologia , Carbacol/uso terapêutico , Cistationina beta-Sintase/metabolismo , Cistationina beta-Sintase/farmacologia , Cistationina beta-Sintase/uso terapêutico , Cistationina gama-Liase/metabolismo , Cistationina gama-Liase/farmacologia , Cistationina gama-Liase/uso terapêutico , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Fator 1 Induzível por Hipóxia/farmacologia , Fator 1 Induzível por Hipóxia/uso terapêutico , Masculino , Malondialdeído , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Sulfetos , Enxofre/metabolismo , Enxofre/farmacologia , Enxofre/uso terapêutico , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Transferases/metabolismo , Transferases/farmacologia , Transferases/uso terapêutico , Bexiga Urinária , Obstrução do Colo da Bexiga Urinária/tratamento farmacológicoRESUMO
Atrazine is a herbicide widely used in the control of weeds in crops such as corn, sugar cane, and sorghum. It is often found in aquatic environments, where it can potentially endanger nontarget organisms such as microalgae. The present study evaluated atrazine toxicity to seven different species of Chlorophyceae and the tolerance of the species to the herbicide was related to morphological, photosynthetic, chlorophyll-a content and the activity of the glutathione-S-transferase enzyme (GST). The comparison of median effect concentration (EC50) values for growth inhibition indicates higher toxicity of atrazine for Pseudopediastrum boryanum and Desmodesmus communis, intermediate toxicity for Ankistrodesmus densus, Chlamydomonas puliminiorfes, and Raphidocelis subcapitata, and lower toxicity for Kirchneriella lunaris and Ankistrodesmus falcatus (EC50: 38, 42, 66, 103, 248, 1004, and 1585 µg L-1 atrazine, respectively). Principal component analysis (PCA) with algal characteristics suggested that the atrazine-sensitive algae P. boryanum and D. communis were positively associated with photosynthetic levels and negatively associated with GST activity and chlorophyll-a concentration. The PCA also suggested that the atrazine-tolerant algae A. falcatus and K. lunaris were positively associated with morphological parameters, where the larger the cell size, the more tolerant. Although it is difficult to associate a single characteristic of algae as the key factor determining the tolerance to atrazine, results presented in this work indicate that the cell area, the photosynthetic parameters (mainly saturating irradiance), chlorophyll-a content, and the biotransformation by GST in combination may be potential predictors for the differential tolerance of Chlorophyceae species to the herbicide. Environ Toxicol Chem 2022;41:1675-1685. © 2022 SETAC.