Format

Send to

Choose Destination
Int Immunopharmacol. 2016 Jun;35:53-60. doi: 10.1016/j.intimp.2016.03.023. Epub 2016 Mar 25.

Alpha-lipoic acid protects mice against concanavalin A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.

Author information

1
Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
2
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.
3
Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: lijinbaoshanghai@163.com.
4
Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: deng_x@yahoo.com.

Abstract

BACKGROUND:

Alpha-lipoic acid (α-LA), which exits in almost all types of prokaryotic and eukaryotic cells, is a key regulator of energy metabolism in mitochondria. This study was designed to explore the protective effect of α-LA against concanavalin A (Con A)-induced hepatitis in mice and explore the potential mechanism.

METHODS:

Acute autoimmune hepatitis was induced by intravenous (IV) injection of Con A (15mg/kg) in C57BL/6 mice. α-LA (100mg/kg) was administered four days before Con A injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological change of the liver tissue were measured. Serum cytokine TNF-α, IL-6, IFN-γ and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the liver were detected by RT-PCR. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) in liver were determined using commercial kits. Phosphorylated NF-κB p65, IκBα and phosphorylated MAPK were measured by Western blot.

RESULTS:

Con A injection induced severe immune responses and extensive hepatocellular apoptosis within 12h. Pretreatment of α-LA markedly reduced the serum ALT and AST activity and the increase of plasma TNF-α, IL-6, IFN-γ and IL-10. In addition, α-LA pretreatment decreased the tissue MPO activity and lipid peroxidation, but increased SOD and GSH levels. α-LA inhibited the phosphorylation of NF-κB p65, IκBα and JNK.

CONCLUSION:

Pretreatment of α-LA markedly attenuated Con A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.

KEYWORDS:

Alpha-lipoic acid; Concanavalin A-induced hepatitis; Reactive oxygen species

PMID:
27018751
DOI:
10.1016/j.intimp.2016.03.023
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center