337 Asphyxial death of several tourists exploring a volcanic crater was attributed to inhalation of mixed gases containing both hydrogen sulfide and carbon dioxide. Hydrogen sulfide is a common by-product of petroleum extraction and refining, as well as a potential hazard from the breakdown of organic materials (hence, its common name, “sewer gas”) overexposure can result from work in confined spaces, submersion in manure pits, 336 or proximity to geothermal or volcanic sources. Courtney Broaddus MD, in Murray & Nadel's Textbook of Respiratory Medicine, 2022 Hydrogen Sulfide ![]() 328 These results have suggested the potential to treat sclerosis in the kidney (both glomerular sclerosis and tubulointerstitial fibrosis), as well as other diseases associated with fibrosis and TGF-β1 (e.g., pulmonary fibrosis) by stimulating H 2S or using another means to form the inactive TGF-β1 monomer. H 2S cleaves the disulfide bond in dimeric active TGF-β1, promoting the formation of inactive TGF- β1 monomer. The H 2S donor NaHS blocked the promotion of EMT by Ang II and TGF-β1 and reduced TGF-β activity. Ang II stimulated TGF-β activation and exogenous TGF-β1–induced EMT. 328 This effect was blocked by a TGF-β receptor kinase inhibitor. ![]() One study has demonstrated that Ang II stimulates EMT in renal tubular epithelial cells by increasing the level of α-smooth actin and decreasing E-cadherin. Ang II- and transforming growth factor beta 1 (TGF-β1)–induced renal tubular epithelial-mesenchymal transition (EMT) plays a pivotal role leading to renal sclerosis. Increases in TGF-β1 are associated with the development of tubulointerstitial fibrosis and glomerular sclerosis in other renal diseases and are mediated, at least in part, by Ang II. 326 H 2S also relaxes smooth muscle by activating ATP-sensitive potassium channels. 325 NaHS-induced vasorelaxation was reduced by removal of the endothelium and by inhibitors of either NO or cGMP production. Incubation with a PKG-1 inhibitor blocked NaHS-stimulated vasodilation. 325 Treatment of the aortic rings with NaHS (an H 2S donor) indicated that a cGMP-dependent protein kinase (PKG) is activated by H 2S. 324 The involvement of cGMP-dependent protein kinase-I in H 2S-induced vasorelaxation was shown in preconstricted aortic rings, with or without intact endothelium. 322 H 2S causes endothelium-dependent/cytochrome P450– dependent vasodilation and vascular smooth muscle hyperpolarization of small arterial vessels, increasing ryanodine-mediated Ca 2+ release through the activation of large conductance calcium activated potassium channels, causing membrane hyperpolarization and vasodilation. 322 Simultaneous infusion of both an inhibitor of CBS and CGL to decrease H 2S production decreased GFR and sodium and potassium excretion, but either inhibitor alone did not affect these renal functions. Infusion of l-cysteine also increases endogenous H 2S production. H 2S plays a role in renal hemodynamics, as shown by the effects of intrarenal infusion of a donor of H 2S (NaHS), which increased renal blood flow and GFR, as well as urinary sodium and potassium excretion. This response was prevented by inhibitors of both CBS and CGL in combination, whereas either inhibitor alone induced only a small decrease in H 2S. ![]() 322,323 Incubation of renal tissue homogenates with l-cysteine as a substrate yields H 2S. 321 H 2S is produced by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL) by the transsulfuration of homocysteine. H 2S generation by kidney cells is reduced in acute and chronic disease states, and H 2S donors ameliorate injury 320 but, under some conditions, H 2S may lead to kidney injury. Yu MB, BChir, in Brenner and Rector's The Kidney, 2020 Hydrogen SulfideĪ growing body of evidence has shown that H 2S, an endogenous bioactive gas synthesized in nearly all organs, plays an important role in the regulation of kidney function.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |