Format

Send to

Choose Destination
Acta Pharmacol Sin. 2014 Dec;35(12):1527-36. doi: 10.1038/aps.2014.119. Epub 2014 Nov 24.

Resveratrol effectively attenuates α-naphthyl-isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms.

Author information

1
1] Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China [2] Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
2
Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
3
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
4
1] Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China [2] State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Abstract

AIM:

α-Naphthylisothiocyanate (ANIT) is a well-characterized cholestatic agent for rats. The aim of this study was to examine whether resveratrol could attenuate ANIT-induced acute cholestasis and liver injury in rats.

METHODS:

SD rats were treated with resveratrol (15 or 30 mg/kg, ip) or a positive control drug ursodeoxycholic acid (100 mg/kg, po) for 5 consecutive days followed by a single dose of ANIT (60 mg/kg, po). Bile flow, and serum biochemical markers and bile constituents were measured 48 h after ANIT administration. Hepatic levels of oxidative repair enzymes (glutathione peroxidase, catalase and MnSOD), myeloperoxidase activity, TNF-α, IL-6 and ATP content, as well as the expression of liver transporter genes and proteins were assayed.

RESULTS:

ANIT exposure resulted in serious cholestasis and liver injury, as shown by marked neutrophil infiltration in liver, dramatically increased serum levels of ALT, AST, GGT, ALP, TBA, TBIL, IBIL and DBIL, and significantly decreased bile excretion and biliary output of GSH and HCO3(-). ANIT significantly increased TNF-α and IL-6 release and myeloperoxidase activity, decreased mitochondrial biogenesis in liver, but had little effect on hepatic oxidative repair enzymes and ATP content. Furthermore, ANIT significantly decreased the expression of Mrp2, FXR and Cyp7a1, markedly increased Mrp3 expression in liver. Pretreatment with resveratrol attenuated ANIT-induced acute cholestasis and liver injury, and other pathological changes. Pretreatment with ursodeoxycholic acid was less effective.

CONCLUSION:

Resveratrol effectively attenuates ANIT-induced acute cholestasis and liver injury in rats, possibly through suppression of neutrophil infiltration, as well as upregulation of expression of hepatic transporters and enzymes, thus decreasing accumulation of bile acids.

PMID:
25418378
PMCID:
PMC4261123
DOI:
10.1038/aps.2014.119
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center