The sirtuin 1 activator SRT1720 alleviated endotoxin-induced fulminant hepatitis in mice

Abstract

The metabolic sensor sirtuin 1 (SIRT1) also functions as a checkpoint in inflammation, and SRT1720 is a highly active and selective SIRT1 activator shown to alleviate inflammatory injury in several recent experimental studies. In the present study, the potential effects and underlying mechanisms of SRT1720 on lipopolysaccharide (LPS)-induced fulminant hepatitis in D-galactosamine (D-Gal)-sensitized mice were investigated. The results indicated that treatment with SRT1720 inhibited LPS/D-Gal-induced elevation of ALT and AST, alleviated the histological abnormalities, suppressed the induction of TNF-α and IL-6, mitigated the phosphorylation of JNK, downregulated the activities of caspase 8, caspase 9 and caspase 3, decreased the level of cleaved caspase 3, reduced the TUNEL-positive cells, and improved the survival rate of the LPS/D-Gal-exposed mice. These data indicated that treatment with the SIRT1 activator SRT1720 alleviated LPS/D-Gal-induced fulminant hepatitis, which might be attributed to the suppressive effects of SRT1720 on TNF-α production and the subsequent activation of the apoptosis cascade.

The role of sirtuin1 in liver injury: molecular mechanisms and novel therapeutic target

“… Kemelo et al (2014) demonstrated a reduction in SIRT1 levels during lipopolysaccharide (LPS)-induced ALI, leading to impaired hepatic function. Subsequently, Zhou et al (2021) corroborated the protective effects of SIRT1 in ALI models. While the majority of investigations have demonstrated the ameliorative impact of SIRT1 activation on liver injury, certain studies have reported a contrasting perspective, suggesting that SIRT1 may contribute to disease progression and exacerbate tissue damage ( Cui et al, 2016 ).…”

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease

“…After equilibrating for 10 min at room temperature, TUNEL reaction solution was added for incubation. After 1 h, the nucleus was re-stained with DAPI, and finally the film was taken 22 .…”

SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease

“…Although the direct effect of activating SIRT1 has been questioned previously [ 62 ], its biological functions in treating different disease models have been intensively studied. For instance, it has been shown to treat cancer [ 10 ], inflammation [ 33 ], ischemia [ 82 ], hepatitis [ 96 ], osteoarthritis [ 59 ], and neurodegeneration [ 6 ], such as Alzheimer's disease. However, the effect of SRT1720 on PD has rarely been studied.…”