Abstract
ObjectiveTo evaluate the impact of mesenchymal stem cells (MSCs) against hepatic I/R injury and explore the role of N-acetyltransferase 8 (NAT8) in the process.MethodsWe investigated the potential of injected MSCs systemically via the tail vein in healing injuried liver of the SD rat model of 70% hepatic I/R injury by measuring the biochemical and pathologic alterations. Subsequently, we evaluated the expression levels of NAT8 by western blotting in vivo. Concurrently, hydrogen peroxide (H2O2)-induced apoptosis in the human normal liver cell line L02 was performed in vitro to evaluate the protective effects of MSC conditioned medium (MSC-CM) on L02 cells. In addition, we downregulated and upregulated NAT8 expression in L02 cells and induced apoptosis by using H2O2 to study the protective role of NAT8.ResultsMSCs implantation led to a significant reduced liver enzyme levels, an advanced protection in the histopathological findings of the acutely injured liver and a significantly lower percentage of TUNEL-positive cells, which were increased after I/R injury. In vitro assays, MSC-CM inhibited hepatocyte apoptosis induced by H2O2. Moreover, overexpression or downregulation of NAT8 prevented or aggravated hepatocyte apoptosis induced by H2O2, respectively.ConclusionsMSC transplantation provides support to the I/R-injured liver by inhibiting hepatocellular apoptosis and stimulating NAT8 regeneration.
Highlights
Ischemia/reperfusion (I/R) injury is responsible for hepatocellular damage during clinical procedures such as liver surgery, hepatic artery ligation, and liver transplantation [1]
The rats were laparotomized after being anesthetized with intraperitoneal pentobarbital sodium (40 mg/kg) and a sterile pediatric vessel loop was placed around the portal triad for 30 min to induce total hepatic ischemia and mesenteric congestion
Characterization of Mesenchymal stem cells (MSCs) After several passages, the adherent cells from umbilical cords (UCs) could form a monolayer of typical fibroblastic and plastic-adherent cells (Fig. 1A)
Summary
Ischemia/reperfusion (I/R) injury is responsible for hepatocellular damage during clinical procedures such as liver surgery, hepatic artery ligation, and liver transplantation [1]. The current therapeutic strategies, comprising pharmacological, genetic, and surgical interventions, for liver damage restoration are limited by side effects and scientific controversies [4]. Mesenchymal stem cells (MSCs) have been reported to show great promise as a novel strategy for the treatment of I/R injury of the intestine [5], liver [6], and kidney [7]. Several studies have suggested that at least some of the therapeutic beneficial effects of MSCs are mediated by its paracrine factors secreted, such as growth factors, cytokines, and chemokines [8,9]. Despite the extensive knowledge regarding the paracrine effects of MSCs, little is known about the influence of MSCs on enzyme expression in the liver
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