Abstract：
:Acetaminophen (APAP) is the most widely used analgesic and its overdose, intentional or unintentional, is known to cause massive oxidative stress and liver tissue damages characterized by hepatocellular apoptosis and hemorrhagic necrosis, leading to acute liver failure (ALF). There has been great interest in the use of antioxidant and anti-inflammatory drugs for the effective treatment of ALF. Manganese porphyrin (MnP), a nonpeptidyl mimic of superoxide dismutase is a promising compound with antioxidant activity, but its application is curtailed by a short half-life in blood. We have recently developed a new family of biodegradable and antioxidant polymeric prodrug, poly(vanillyl alcohol-co-oxalate) (PVAX), which is able to scavenge H2O2 and release antioxidant and anti-inflammatory vanillyl alcohol. In this work, we developed MnP-loaded PVAX particles and evaluated their potential as antioxidant and anti-inflammatory therapeutic agents for APAP-induced ALF. PVAX particles and MnP showed synergistic antioxidant and anti-inflammatory activities in macrophages stimulated with LPS (lipopolysaccharide). Animal studies using a mouse model of APAP-induced ALF revealed that MnP-loaded PVAX particles significantly reduced the serum ALT level and protected liver damages. We anticipated that MnP-loaded PVAX particles have great potential as a therapeutic agent for oxidative stress-associated diseases such as APAP-induced ALF.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Ko E,Jeong D,Kim J,Park S,Khang G,Lee Ddoi
10.1016/j.biomaterials.2014.01.048subject
Has Abstractpub_date
2014-04-01 00:00:00pages
3895-902issue
12eissn
0142-9612issn
1878-5905pii
S0142-9612(14)00064-7journal_volume
35pub_type
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