Enhanced effect of recombinant human soluble thrombomodulin by ultrasound irradiation in acute liver failure

Abstract

The administration of recombinant human soluble thrombomodulin (rhsTM) significantly improves liver inflammation and increases the survival rate of patients with acute liver failure (ALF). However, rhsTM is dose-dependently correlated to the risk of bleeding. Recently, ultrasound (US) was found to enhance the effect of various drugs. Thus, the present study aimed to determine the enhancement effect of US irradiation on rhsTM in ALF. rhsTM (1 mg/kg) and US (1 MHz, 0.3 W/cm 2 ) were irradiated to the liver of lipopolysaccharide/D-galactosamine-induced ALF mice model. The post-treatment aspartate aminotransferase, alanine aminotransferase, and high-mobility group box 1 levels were significantly lower in the rhsTM + US group than in the rhsTM alone group. Histopathological findings revealed significantly reduced liver injury and apoptosis in the rhsTM + US group. By contrast, US irradiation had no effect on rhsTM and TNF-α concentration in the liver tissue. In conclusion, US irradiation enhanced the effect of rhsTM in the ALF mice model. However, further studies must be conducted to determine the exact mechanism of such enhancement effect.

Changes in platelet levels and prognosis in patients with acute liver failure and late-onset hepatic failure

“…[24] Administration of rTM can attenuate the inflammatory response and liver injury in a model of acute liver injury. [25,26] Interestingly, suppression of the inflammatory response by thrombomodulin occurs independently of coagulation inhibition. [24] The administration of rTM to ALF patients may suppress the inflammatory pathway by modulating platelet and monocyte activation in the liver.…”

The Role of IL-35 in the Pathophysiological Processes of Liver Disease

“…Interleukin-35 and Acute Liver Injury Failure ALF, also known as a life-threatening clinical syndrome of fulminant liver failure, has the common characteristic of the activation of inflammatory cells (Hoshino et al, 2020). The overall survival of ALF patients was 67%, and approximately 30% of these patients had an experience of liver transplantation operation (Mohamadi-Zarch et al, 2020).…”

Interleukin-35 and Thymoquinone nanoparticle-based intervention for liver protection against paracetamol-induced liver injury in rats

“…Earlier revisions illustrated that IL-35 has various roles in disease pathogenesis such as rheumatoid arthritis ( Ning et al, 2015 ), autoimmune encephalomyelitis, uveitis ( Wang et al, 2014 ), Hashimoto’s thyroiditis ( Yilmaz et al, 2016 ), multiple low dose streptozotocin ( Singh et al, 2015 ), allergic rhinitis ( Suzuki et al, 2017 ), liver disease ( Yang et al, 2020a ), cardiovascular diseases ( Posadas-Sánchez et al, 2017 ), and asthma ( Kanai et al, 2017 ). Anti-inflammatory and pro-inflammatory processes are involved in the developing liver disorders, suggesting that IL-35 may produce a noteworthy effect in the advance of liver diseases via immunosuppressive regulations ( Hu et al, 2021 , Hoshino et al, 2020 ).…”