RGD Reference Report - Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia. - Rat Genome Database

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Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia.

Authors: Lu, LS  Wu, CC  Hung, LM  Chiang, MT  Lin, CT  Lin, CW  Su, MJ 
Citation: Lu LS, etal., Liver Int. 2007 May;27(4):529-37.
RGD ID: 1601171
Pubmed: PMID:17403193   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1478-3231.2007.01451.x   (Journal Full-text)

Background: This study addressed the effects of apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, on hepatic oxidative burden and liver injury during diet-induced hypercholesterolaemia. Methods and Results: Male Wistar rats were fed a 4% cholesterol-enriched diet for 3 weeks. Apocynin was administered in drinking water concurrently. The high-cholesterol diet (HC) significantly increased the serum level of cholesterol and hepatic cholesterol ester deposition, and these parameters were similar between the HC and high-cholesterol diet plus apocynin (HCA) groups. The HC group showed abnormal liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (Alk-P)] as well as increased Evans blue extravasation and macrophages infiltration. Apocynin treatment could suppress these inflammation-related parameters. In vivo measurement of NADPH-derived cellular autofluorescence suggested that HC increased oxidative stress in hepatocytes. Biochemical analysis of redox status including thiobarbituric acid reactive substances, reduced glutathione, and oxidized glutathione also confirmed the phenomenon. Apocynin treatment was able to alleviate these indices of oxidative burden owing to HC. Furthermore, apocynin-abrogated HC induced gp91(phox) expression, suggesting the involvement of NADPH oxidase in the pathogenesis. Conclusions: We concluded that apocynin suppressed NADPH oxidase activation and subsequent liver injuries owing to high-cholesterol intake in rats. The impacts of cholesterol metabolism disorders on pathogenesis and progression of steatohepatitis warrant further clinical investigation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypercholesterolemia  ISOAlpl (Rattus norvegicus)1601171; 1601171 RGD 
Hypercholesterolemia  IEP 1601171 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Alpl  (alkaline phosphatase, biomineralization associated)

Genes (Mus musculus)
Alpl  (alkaline phosphatase, liver/bone/kidney)

Genes (Homo sapiens)
ALPL  (alkaline phosphatase, biomineralization associated)


Additional Information