Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia

Long Sheng Lu, Chau Chung Wu, Li Man Hung, Meng Tsan Chiang, Ching Ting Lin, Chii Wann Lin, Ming Jai Su

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)529-537
Number of pages9
JournalLiver International
Volume27
Issue number4
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Fingerprint

Hypercholesterolemia
Cholesterol
Liver
Diet
Wounds and Injuries
NADP
Oxidoreductases
acetovanillone
Evans Blue
Glutathione Disulfide
Thiobarbituric Acid Reactive Substances
Cholesterol Esters
Liver Function Tests
Fatty Liver
Aspartate Aminotransferases
Alanine Transaminase
Drinking Water
Oxidation-Reduction
Glutathione
Alkaline Phosphatase

Keywords

  • Apocynin
  • Cholesterol
  • Gp91
  • Liver injury
  • NADPH oxidase

ASJC Scopus subject areas

  • Hepatology

Cite this

Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia. / Lu, Long Sheng; Wu, Chau Chung; Hung, Li Man; Chiang, Meng Tsan; Lin, Ching Ting; Lin, Chii Wann; Su, Ming Jai.

In: Liver International, Vol. 27, No. 4, 05.2007, p. 529-537.

Research output: Contribution to journalArticle

Lu, Long Sheng ; Wu, Chau Chung ; Hung, Li Man ; Chiang, Meng Tsan ; Lin, Ching Ting ; Lin, Chii Wann ; Su, Ming Jai. / Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia. In: Liver International. 2007 ; Vol. 27, No. 4. pp. 529-537.
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AB - 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.

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