The Pathophysiology of H2S in Renal Glomerular Diseases

Abstract

Renal glomerular diseases such as glomerulosclerosis and diabetic nephropathy often result in the loss of glomerular function and consequently end-stage renal disease. The glomerulus consists of endothelial cells, mesangial cells and glomerular epithelial cells also referred to as podocytes. A fine-tuned crosstalk between glomerular cells warrants control of growth factor synthesis and of matrix production and degradation, preserving glomerular structure and function. Hydrogen sulfide (H2S) belongs together with nitric oxide (NO) and carbon monoxide (CO) to the group of gasotransmitters. During the last three decades, these higher concentration toxic gases have been found to be produced in mammalian cells in a well-coordinated manner. Recently, it became evident that H2S and the other gasotransmitters share common targets as signalling devices that trigger mainly protective pathways. In several animal models, H2S has been demonstrated as a protective factor in the context of kidney disorders, in particular of diabetic nephropathy. Here, we focus on the synthesis and action of H2S in glomerular cells, its beneficial effects in the glomerulus and its action in the context of the other gaseous signalling molecules NO and CO.

The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders

“…The causes of AKI can be various factors, including sepsis, glomerulonephritis, medication (e.g., NSAIDs, cisplatin), liver failure, heart failure, ischemia and reperfusion syndrome, etc. [ 160 ]. The latter factor is one of the most frequent in the development of this pathological condition and is associated with the development of fibrosis and inflammation in the kidneys and, as a result, acute impairment of their function [ 161 ].…”

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“…However, currently available agents are still limited ( Table 1 ) and despite their considerable merits, multiple concerns were raised concerning the use of these inhibitors, specifically those targeting RIPK1. The first issue associated with RIPK1 inhibitors like wogonin and PPBICA is their low water solubility and limited bioavailability ( Baek et al, 2018 ; Liu et al, 2022 ), together with cardiovascular problems of hydrogen sulfide ( Beck and Pfeilschifter, 2022 ), all of which greatly limits the clinical application and translation of these agents. Likewise, the first identified RIPK1 inhibitor, Necrostatin-1 has somehow limited utility due to low solubility, short half-life of about 1 h along with narrow structure–activity relationship profile ( Degterev et al, 2008 ; Oliveira et al, 2018 ; Wang et al, 2019 ).…”

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“…Similar to other gasotransmitters, H 2 S is endogenously produced by different enzymes in mammalian cells ( Figure 1 D). Cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) are well-characterised enzymes of the transsulfuration pathway that produce H 2 S by a complex biochemical cascade using L-cysteine or L-homocysteine as substrates (for review see: [ 24 , 25 ]). In analogy to the enzymes involved in NO ∙ and CO synthesis, the regulation of CSE and CBS expression or activity occurs on different levels.…”