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


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.
Lu
Long-Sheng
LS
Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Wu
Chau-Chung
CC
Hung
Li-Man
LM
Chiang
Meng-Tsan
MT
Lin
Ching-Ting
CT
Lin
Chii-Wann
CW
Su
Ming-Jai
MJ
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood; D022781:Hepatocytes; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000517:prevention & control; D008107:Liver Diseases / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D019255:NADPH Oxidases; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000098:Acetophenones; D000975:Antioxidants; D002784:Cholesterol; C056165:acetovanillone; D019255:NADPH Oxidases