RESUMO
Aims. The study aimed to examine whether hydrogen sulfide (H2S) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. Results. H2S levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known H2S-producing enzymes in kidney, cystathionine γ-lyase (CSE) and cystathionine-ß-synthase (CBS), decreased significantly during ageing. Chronic H2S donor (NaHS, 50 µmol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition. These protective effects may relate to transcription factor Nrf2 activation and antioxidant proteins such as HO-1, SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS treatment. Furthermore, the expression of H2S-producing enzymes changed with exogenous H2S administration and contributed to elevated H2S levels in the ageing kidney. Conclusions. Endogenous hydrogen sulfide production in the ageing kidney is insufficient. Exogenous H2S can partially rescue ageing-related kidney dysfunction by reducing oxidative stress, decreasing collagen deposition, and enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide production may also contribute to the beneficial effects of NaHS treatment.
Assuntos
Envelhecimento/metabolismo , Sulfeto de Hidrogênio/metabolismo , Rim/efeitos dos fármacos , Sulfetos/farmacologia , Transporte Ativo do Núcleo Celular , Fatores Etários , Envelhecimento/sangue , Envelhecimento/patologia , Envelhecimento/urina , Animais , Apoptose/efeitos dos fármacos , Colágeno/metabolismo , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Fibrose , Heme Oxigenase-1/metabolismo , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/urina , Rim/metabolismo , Rim/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Sulfetos/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/metabolismoRESUMO
Aims. To examine whether hydrogen sulfide (H2S) generation changed in ageing diabetic mouse hearts. Results. Compared to mice that were fed tap water only, mice that were fed 30% fructose solution for 15 months exhibited typical characteristics of a severe diabetic phenotype with cardiac hypertrophy, fibrosis, and dysfunction. H2S levels in plasma, heart tissues, and urine were significantly reduced in these mice as compared to those in controls. The expression of the H2S-generating enzymes, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, was significantly decreased in the hearts of fructose-fed mice, whereas cystathionine-ß-synthase levels were significantly increased. Conclusion. Our results suggest that this ageing diabetic mouse model developed diabetic cardiomyopathy and that H2S levels were reduced in the diabetic heart due to alterations in three H2S-producing enzymes, which may be involved in the pathogenesis of diabetic cardiomyopathy.
Assuntos
Envelhecimento , Sulfeto de Hidrogênio/metabolismo , Miocárdio/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Glucose/farmacologia , Coração/efeitos dos fármacos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/farmacologia , Sulfurtransferases/metabolismoRESUMO
The UK Health and Safety Executive has investigated several incidents of workplace accidents involving hydrogen sulphide exposure in recent years. Biological monitoring has been used in some incidents to determine the cause of unconsciousness resulting from these incidents and as a supporting evidence in regulatory enforcement. This paper reports on three case incidents and discusses the use of biological monitoring in such cases. Biological monitoring has a role in identifying hydrogen sulphide exposure in incidents, whether these are occupational or in the wider environment. Sample type, time of collection and sample storage are important factors in the applicability of this technique. For non-fatal incidents, multiple urine samples are recommended at two or more time points between the incident and 15 h post-exposure. For routine occupational monitoring, post-shift samples should be adequate. Due to endogenous levels of urinary thiosulphate, it is likely that exposures in excess of 12 ppm for 30 min (or 360 ppm/min equivalent) would be detectable using biological monitoring. This is within the Acute Exposure Guideline Level 2 (the level of the chemical in air at or above which there may be irreversible or other serious long-lasting effects or impaired ability to escape) for hydrogen sulphide.