Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

Abstract

As a convenient, effective and economical kidney replacement therapy for end‐stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long‐term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose‐induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen‐rich peritoneal dialysate. In addition, in vitro studies of high glucose‐induced peritoneal fibrosis were performed using MeT‐5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti‐peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.

Mitochonic acid-5 ameliorates chlorhexidine gluconate-induced peritoneal fibrosis in mice

“…Oxidative stress triggers inflammatory conditions, including macrophage infiltration in the peritoneum, and mitochondria are a major site for the production of reactive oxygen species (ROS) [6,14,24,25]. As for the mechanism of the effects of MA-5 on mitochondria, previous studies have shown that MA-5 binds to mitofilin, an inner mitochondrial membrane protein, and induces ATP synthase oligomerization, supercomplex formation, and a conformational change in cristae [26].…”

“…Mitochondrial dysfunction has been reported to cause peritoneal fibrosis via increased oxidative stress [6,[12][13][14], and MA-5 recovers mitochondrial function by reducing oxidative stress in kidney tissues and cardiac myocytes [18]. Therefore, we assessed the mitochondrial component expression level in the peritoneal tissues by performing immunohistochemistry of ATP5a1 and UCP2, both of which play an important role in mitochondrial function (Fig.…”

“…Mitochondrial dysfunction causes increased oxidative stress and plays an important role in fibrosis in organs such as the lungs [7,8], liver [9,10], and kidneys [11] by increasing the production of cytokines, such as transforming growth factor β (TGF-β), by macrophages and the activation of myofibroblasts. Additionally, mitochondrial dysfunction contributes to peritoneal fibrosis by increasing oxidative stress [6,[12][13][14].…”

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient’s Health)

“…Terawaki et al [ 131 ] could reduce peritoneal and systemic oxidative stress without any side effects by single administration of H2-enriched dialysate. Hongtao et al [ 132 ] recently showed that in a mouse model, after the induction of peritoneal fibrosis by a high-glucose solution, treatment with hydrogen-rich peritoneal dialysate exerted an antiperitoneal fibrotic effect, suggested to occur through the ROS/PTEN/AKT/mTOR pathway. These observations highlight the need for H2–PD clinical trials in the future.…”

Status and factors related to post‐traumatic growth in continuous ambulatory peritoneal dialysis: A multi‐centre study

“…Types of PD include intermittent peritoneal dialysis, continuous cycling PD and continuous ambulatory peritoneal dialysis (CAPD). CAPD, a method of uninterrupted dialysis, is one of the main treatment options for end-stage renal disease (Lu et al, 2020). Although CAPD is effective in eliminating metabolic waste and correcting acid, alkali, water and electrolyte-related disorders, it often disrupts daily routines, hinders quality of life and elicits a range of emotional experiences (Ruiz et al, 2017).…”