Abstract
Sepsis-induced acute kidney injury (AKI) is a severe complication of sepsis and an important cause of mortality in septic patients. Previous investigations showed that methane had protective properties against different diseases in animal models. This study is aimed at investigating whether methane-rich saline (MRS) has a protective effect against sepsis-induced AKI. Sepsis was induced in wild-type C57BL/6 mice by cecal ligation and puncture (CLP), and the mice were divided into three groups: a sham control group (sham), a surgery group with saline intraperitoneal injection (i.p.) treatment (CLP + NS), and a surgery group with MRS i.p. treatment (CLP + MRS). 24 h after the establishment of the sepsis, the blood and kidney tissues of mice in all groups were collected. According to the serum levels of blood urea nitrogen (BUN) and creatinine (CRE) and a histologic analysis, which included hematoxylin-eosin (H&E) staining and periodic acid-Schiff (PAS) staining, MRS treatment protected renal function and tissues from acute injury. Additionally, MRS treatment significantly ameliorated apoptosis, based on the levels of apoptosis-related protein makers, including cleaved caspase-3 and cleaved PARP, and the levels of Bcl-2/Bax expression and TUNEL staining. In addition, the endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP)/caspase-12 apoptosis signaling pathway was significantly suppressed in the CLP + MRS group. The levels of inflammation and oxidative stress were also reduced after MRS treatment. These results showed that MRS has the potential to ameliorate sepsis-induced acute kidney injury through its anti-inflammatory, antioxidative, and antiapoptosis properties.
Highlights
Sepsis-induced acute kidney injury (AKI) is a severe complication of sepsis and a leading cause of mortality in intensive care unit (ICU) patients
Recent research has suggested that apoptosis and immune suppression, especially the apoptosis of tubular cells, may Oxidative Medicine and Cellular Longevity be involved in the pathological process of septic AKI, which is quite different from the other types of AKI [7]
Elevated levels of blood urea nitrogen (BUN) and CRE were observed after the establishment of the cecal ligation and puncture (CLP) model, confirming that the sepsis model was successfully constructed (Figure 1)
Summary
Sepsis-induced acute kidney injury (AKI) is a severe complication of sepsis and a leading cause of mortality in intensive care unit (ICU) patients. The morbidity of acute renal injury can be up to 70%, and approximately 5% of these patients progress to acute renal failure during their hospital stays. The overall ICU mortality rate of acute renal failure is approximately 50%, and 15% of survivors continued to rely on renal replacement therapy (RRT) after they were discharged. The leading cause of acute kidney injury is sepsis, which contributes to the 50% of the incidence [1,2,3,4]. Despite advances in clinical treatment and intensive care, there is currently no specific therapy for septic AKI; the early onset of RRT may reduce mortality [5]. Recent research has suggested that apoptosis and immune suppression, especially the apoptosis of tubular cells, may Oxidative Medicine and Cellular Longevity be involved in the pathological process of septic AKI, which is quite different from the other types of AKI [7]
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