Hydrogen sulfide ameliorates chronic renal failure in rats by inhibiting apoptosis and inflammation through ROS/MAPK and NF-κB signaling pathways

Abstract

Chronic renal failure (CRF) is a major public health problem worldwide. Hydrogen sulfide (H2S) plays important roles in renal physiological and pathophysiological processes. However, whether H2S could protect against CRF in rats remains unclear. In this study, we found that H2S alleviated gentamicin-induced nephrotoxicity by reducing reactive oxygen species (ROS)-mediated apoptosis in normal rat kidney-52E cells. We demonstrated that H2S significantly improved the kidney structure and function of CRF rats. We found that H2S decreased the protein levels of Bax, Caspase-3, and Cleaved-caspase-3, but increased the expression of Bcl-2. Treatment with H2S reduced the levels of malondialdehyde and ROS and increased the activities of superoxide dismutase and glutathione peroxidase. H2S significantly abolished the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38 in the kidney of CRF rats. Furthermore, H2S decreased the expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-10, and monocyte chemoattractant protein-1, as well as the protein levels of p50, p65, and p-p65 in the kidney of CRF rats. In conclusion, H2S could ameliorate adenine-induced CRF in rats by inhibiting apoptosis and inflammation through ROS/mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.

Candesartan and epigallocatechin‐3‐gallate ameliorate gentamicin‐induced renal damage in rats through p38‐MAPK and NF‐κB pathways

“…NF‐κB represents a cornerstone of the inflammatory process during nephrotoxicity that is activated in response to ROS . A recent study indicated that the expression of NF‐κB was upregulated in the kidney of rats administered gentamicin . This result is in accordance with our study.…”

“…Notably, ROS has been demonstrated to activate mitogen‐activated protein kinases (MAPK) pathway, which consecutively mediates apoptotic cell death . Some studies have shown that redox‐sensitive biological signaling agents, such as nuclear factor‐kappa B (NF‐κB) and its upstream‐related kinases including p38‐MAPK, as well as activation of apoptosis, are involved in nephrotoxicity caused by gentamicin .…”

“…Notably, ROS has been demonstrated to activate mitogen‐activated protein kinases (MAPK) pathway, which consecutively mediates apoptotic cell death . Some studies have shown that redox‐sensitive biological signaling agents, such as nuclear factor‐kappa B (NF‐κB) and its upstream‐related kinases including p38‐MAPK, as well as activation of apoptosis, are involved in nephrotoxicity caused by gentamicin . So, as a result, the use of different agents mitigating oxidative stress, inflammation, and apoptosis or an agent that has several mechanisms of action may successfully present a promising preventive strategy against gentamicin‐induced nephrotoxicity …”

Early urinary biomarkers of renal tubular damage by a high‐salt intake independent of blood pressure in normotensive rats

“…Until now, it has been widely accepted that a relatively high level of ROS causes redox imbalance, which induces cell apoptosis or necrosis under a wide variety of physiological and pathological conditions . Recent studies have proven that ROS can activate MAPKs, and apoptotic cell death induced by ROS is mediated by the p38MAPK pathway in lung and renal cells. Interestingly, in the kidney of CKD rats, the levels of ROS were markedly increased, the activities of anti‐oxidative enzymes, SOD and GSH‐Px, were significantly decreased, and ROS could induce apoptosis …”

“…Recent studies have proven that ROS can activate MAPKs, and apoptotic cell death induced by ROS is mediated by the p38MAPK pathway in lung and renal cells. Interestingly, in the kidney of CKD rats, the levels of ROS were markedly increased, the activities of anti‐oxidative enzymes, SOD and GSH‐Px, were significantly decreased, and ROS could induce apoptosis …”