Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure

Abstract

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.

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

“…The present meta-analysis showed that the biochemical variables, including ALT, ALB, AST, TBIL and A/G, which were significantly improved by combination therapy during Tα1 add-on, compared with ETV monotherapy, thus indicating that the combination treatment have a better effect on improving the function of hepatocytes and remission of hepatic damage. Yang XL [15] found that Tα1 could protect liver of rat against damage via down-regulating TNF-α and up-regulating IL-10, resulting in the relief to hepatic inflammation and hepatocyte apoptosis, which was also in line with our findings.…”

“…Tα1 is a synthetic polypeptide consisting of 28 amino acids, which can not only reduce hepatic inflammation, but also trigger the maturation in lymphocytes and promote T-helper 1 (Th1) response [14,15]. Tα1 has reflected good therapeutic activities and little side effect with viral hepatitis [16][17][18][19].…”

The clinical efficacy and adverse effects of Entecavir plus Thymosin alpha-1 combination therapy versus Entecavir Monotherapy in HBV-related cirrhosis: a systematic review and meta-analysis

“…The results indicated that the combination treatment had a better effect on the improvement in the function of hepatocytes and remission of hepatic damage. Yang XL [15] found that Tα1 could protect liver of rat against damages via down-regulating TNF-α and upregulating IL-10, and result in a relief of hepatic inflammation and hepatocyte apoptosis, which was also in line with our findings.…”

The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

“…The results indicated that the combination treatment had a better effect on the improvement in the function of hepatocytes and remission of hepatic damage. Yang XL [15] found that Tα1 could protect liver of rat against damages via down-regulating TNF-α and up-regulating IL-10, and result in a relief of hepatic in ammation and hepatocyte apoptosis, which was also in line with our ndings.…”

“…Tα1 is a synthetic polypeptide consisting of 28 amino acids, which can not only reduce hepatic in ammation, but also promote the maturation in T lymphocytes and the activation of T-helper 1 (Th1) [14,15]. Tα1 has shown good therapeutic activities and has rarely caused adverse reactions such as transient muscular atrophy, multiple joint pains with edema and rash in patients with viral hepatitis [16][17][18][19].…”