Abstract
Both oxidative stress (OS) and inflammation are two fundamental pathological processes of acute liver injury (ALI). The current work is to investigate the effect and possible mechanism of Uncaria rhynchophylla (UR) on thioacetamide- (TAA-) induced ALI in rats. UR (100 and 200 mg/kg) was orally administrated with TAA (200 mg/kg of bodyweight, intraperitoneal injection) for 3 consecutive days. ALI was confirmed using histological examination and the factors associated with OS and liver function activity measured in serum. Moreover, expressions of inflammation and collagen-related proteins were measured by the Western blot analysis. Myeloperoxidase (MPO), which mediates OS in the ALI control group, was manifested by a significant rise compared with the normal group. UR significantly reduced AST, ALT, and ammonia levels in serum. The nuclear factor-κB (NF-κB) activation induced by TAA led to increase both inflammatory mediators and cytokines. Whereas, UR administration remarkably suppressed such an overexpression. UR supplementation improved matrix metalloproteinases (MMPs) such as MMP-1, -2, and -8. In contrast, tissue inhibitors of metalloproteinases- (TIMP-) 1 level increased significantly by UR treatment. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously by UR treatment. UR may ameliorate the effects of TAA-induced ALI in rats by suppressing both OS through MPO activation and proinflammatory factors through NF-κB activation. In conclusion, UR exhibited a potent hepatoprotective effect on ALI through the suppression of OS.
Highlights
A recent study reported the distribution of matrix metalloproteinases (MMPs)-1, matrix metallopeptidase- (MMP-)2, and MMP-8 is related to inflammatory disease
Rabbit polyclonal antibodies against hemeoxygenase1 (HO-1); goat polyclonal antibodies against tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β); mouse monoclonal antibodies against inhibitor of nuclear factor kappa B alpha (IκBα), nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), nuclear factor-kappa B p65 (NF-κBp65), and tissue inhibitors of metalloproteinases (TIMP)-1; and mouse polyclonal antibodies against phosphoinhibitor of nuclear factor kappa B alpha (p-IκBα), cycloxygenase-2 (COX-2), matrix metallopeptidase- (MMP-) 1, MMP-2, MMP-8, histone, and β-actin were purchased from Santa Cruz Biotechnology, Inc. (Dallas, TX, USA)
Our results in this study revealed that Uncaria rhynchophylla (UR) significantly inhibited the expression of MMP-1, -2, and -8 (p < 0.01, p < 0.001, and p < 0.01, respectively); otherwise, it significantly elevated tissue inhibitors of metalloproteinases- (TIMP-)1 (p < 0.05). e data suggested that UR improved TAAinduced acute liver injury through the inhibition of extracellular matrix (ECM) degradation
Summary
E liver is composed of several cell types including hepatocytes, Kupffer cells, stellate cells, biliary epithelial cells, and liver sinusoidal endothelial cells Each of these cell types possesses special functions and cooperatively regulates hepatic function, such as the balance of metabolism [1]. Acute liver injury (ALI) has been reported to cause by various reasons, which can induce inflammation and necrosis of liver cells [2]. A series of inflammatory response is mediated by the activation of NF-κB, which plays as an important inducer of inflammation and regulates inflammatory response [7, 8]. A recent study reported the distribution of MMP-1, MMP-2, and MMP-8 is related to inflammatory disease These factors’ regulation is considered important to maintain the balance between MMPs and their tissue inhibitors (TIMPs) for tissue homeostasis [11].
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