Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure
نویسندگان
چکیده
The present study aimed to evaluate whether thymosin α1 (Tα1) increases survival rates through the improvement of immunofunction and inhibition of hepatocyte apoptosis in rats with acute liver failure (ALF). A total of 25 rats were randomly divided into the control group (CG), the model group (MG) and the treatment group (TG). The CG received an intraperitoneal injection of saline (2 ml). The ALF rat model was established by the intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 µg/kg). The TG received an intraperitoneal injection of Tα1 (0.03 mg/kg) 1 h prior to and 30 min after modeling. The survival rates of the rats were recorded. An additional 63 rats were randomly divided into a CG (n=3), MG (n=30) and TG (n=30). Three rats were sacrificed at 3, 6, 9 and 12 h after establishment of the rat model to detect plasma alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10). Liver samples were stained with hematoxylin and eosin and TUNEL, and reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to detect B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in liver tissue. The results indicated that the survival rate of the TG was significantly higher compared with that of the MG at 24 h (P<0.05). Plasma ALT, AST and TBIL in the MG and TG increased over time (3-12 h), with ALT, AST and TBIL observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05). Hepatocellular necrosis, hemorrhage and inflammatory cell infiltration of ALF were aggravated over time (3-12 h) in the MG and TG. Notably, in the Tα1-treated rats, the hepatocytes appeared healthier with fewer apoptotic cells compared with those from the MG at the same time-points. Hepatocyte apoptotic index increased in the TG and MG, but was significantly lower in the TG compared with the MG at each time-point (P<0.05) in TUNEL assays. Plasma TNF-α and IL-10 in the MG and TG increased over time (3-12 h), with TNF-α observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05), however, IL-10 was observed to be significantly higher in the TG compared with the MG at each time-point (P<0.05). Bax mRNA expression was significantly lower in the TG compared with the MG at each time-point (P<0.05), whereas Bcl-2 was significantly higher (P<0.05). In conclusion, Tα1 improved survival rates in an ALF rat model by downregulating TNF-α and upregulating IL-10, leading to the attenuation of hepatic inflammation and hepatocyte apoptosis.
منابع مشابه
0083. Hepatoprotective effects of hydrogen sulphide against acute liver failure
Introduction Acute liver failure is a fatal syndrome attributed to massive hepatocyte apoptosis that is resistant to conventional medical therapies. Consequently, liver transplantation is required in many cases. An experimental liver failure model induced by galactosamine (Gal) and lipopolysaccharide (LPS) mimics clinical acute liver failure. In this model, LPS stimulates macrophages to release...
متن کاملHepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice.
Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously, we found that the extracts of Elaeagnus mollis leaves had favorable protective effects on acute ...
متن کاملGlyphosate Poisoning with Acute Fulminant Hepatic Failure
Background: Glyphosate containing herbicides are widely used the world over. They are marketed as nontoxic to humans, but numerous studies have showed that these glyphosate-based herbicides (GlySH) can cause multiorgan damage.1 Recent reports of animal studies on rats have raised a doubt of liver damage after long term exposure to GlySH. Case Presentation: a young male had chronic exposure to G...
متن کاملThymosin-β4 inhibits proliferation and induces apoptosis of hepatic stellate cells through PI3K/AKT pathway
Liver fibrosis is a necessary stage for chronic liver diseases, and serious threat to human health. Hepatic fibrosis is a necessary stage for chronic liver diseases. Hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Thymosin beta 4 (Tβ4) has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs, ho...
متن کاملRecent Technological Advances in Hepatogenic Differentiation of Stem Cells Relevant to Treatment of Liver Diseases
Liver failure, in an acute or chronic form, is a growing health problem ranking as one of the leading causes of death worldwide. Inborn errors of metabolism characterized by defects in hepatic enzymes or other proteins with metabolic functions, such as receptors or transporters accompanied with environmental factors involve etiology and presentation of liver failure. Currently, the only establi...
متن کامل