Abstract
This study investigated the potential hepatoprotective effect of oligoribonucleotides-d-mannitol complexes (ORNs-d-M) against thioacetamide (TAA)-induced hepatotoxicity in mice. The hepatoprotective activity of ORNs-d-M was evaluated in thioacetamide (TAA)-treated C57BL/6J. Results indicate that treatment with ORNs-d-M displayed a protective effect at the TAA-induced liver injury. Treatment with ORNs-d-M, starting at 0 h after the administration of TAA, decreased TAA-elevated serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT). Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx), and levels of glutathione (GSH), were enhanced with ORNs-d-M administration, while the hepatic oxidative biomarkers (TBA-reactive substances, protein carbonyl derivatives, protein-SH group) and myeloperoxidase (MPO) activity were reduced. Furthermore, genetic analysis has shown that the ORNs-d-M decreases the expression of mRNA pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), profibrogenic cytokine-transforming growth factor β1 (TGF-β1), as well as the principal protein of the extracellular matrix—collagen I. The present study demonstrates that ORNs-d-M exerts a protective effect against TAA-induced liver injury, which may be associated with its anti-inflammatory effects, inhibition of overexpression of mRNA cytokines, and direct effects on the metabolism of the toxin.
Highlights
The liver acts as the main metabolic organ where the major biochemical processes involved in maintaining the homeostasis of an organism are integrated
Acute toxic liver injury is characterized by membrane damage, oxidative stress, massive necrosis of hepatocytes, infiltration of parenchyma by neutrophils and activation of hepatic stellate cells, following an increased inflammation and damage to the liver [2]
The thioacetamide (TAA)-treated group demonstrated a notable elevation of ALT and GGT levels in serum compared to the control group (p < 0.05)
Summary
The liver acts as the main metabolic organ where the major biochemical processes involved in maintaining the homeostasis of an organism are integrated. Acute toxic liver injury is characterized by membrane damage, oxidative stress, massive necrosis of hepatocytes, infiltration of parenchyma by neutrophils and activation of hepatic stellate cells, following an increased inflammation and damage to the liver [2]. This is a key event in inducing liver damage. Activated hepatic stellate cells overexpress the components of the extracellular matrix (ECM), including fibril-forming type I and III collagens, and laminin This overexpression leads to the deposition of collagen contributing to the development of liver fibrosis [5]
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