Basic Research
Copyright ©The Author(s) 2002. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2002; 8(4): 728-733
Published online Aug 15, 2002. doi: 10.3748/wjg.v8.i4.728
Hepatoprotective role of ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice
Guo-Liang Zhang, Ye-Hong Wang, Wei Ni, Hui-Ling Teng, Zhi-Bin Lin
Guo-Liang Zhang, Ye-Hong Wang, Wei Ni, Hui-Ling Teng, Zhi-Bin Lin, Department of Pharmacology, School of Basic Medical Sciences, Beijing University, Beijing 100083, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No.39770861, No.30171097; Beijing University Center For Human Disease Genomics Research Foundation, No.2000-A-1; and JANSSEN Science Research Foundation
Correspondence to: Dr. Guo-Liang Zhang, Department of Pharmacology, School of Basic Medical Sciences, Beijing University, Beijing 100083, China.
Telephone: +86-10-62091421 Fax: +86-10-62015681
Received: March 12, 2002
Revised: April 15, 2002
Accepted: April 23, 2002
Published online: August 15, 2002

AIM: To examine the effect of ganoderma lucidum polysaccharide (GLP) on the immune liver injury induced by BCG infection, and investigate the relationship between degrees of hepatic damage and NO production in mice.

METHODS: Immune hepatic injury was markedly induced by BCG-pretreatment (125 mg·kg-1, 2-week, iv) or by BCG-pretreatment plus lipopolysaccharide (LPS, 125 μg·kg-1, 12-hour, iv) in mice in vivo. Hepatocellular damage induced by BCG-pretreated plus inflammatory cytokines mixture (CM), which was included TNF-α, IL-1β, IFN-γ and LPS in culture medium in vitro. Administration of GLP was performed by oral or incubating with culture medium at immune stimuli simultaneity. Liver damage was determined by activity of alanine aminotransferase (ALT) in serum and in hepatocytes cultured supernatant, by liver weight changes and histopathological examination. NO production in the cultured supernatant was determined by the Griess reaction. Moreover, inducible nitric oxide synthase (iNOS) protein expression was also examinated by immunohistochemical method.

RESULTS: Immune hepatic injury was markedly induced by BCG or BCG plus inflammatory cytokines in BALB/c mice in vivo and in vitro. Under BCG-stimulated condition, augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well as granuloma forming and inflammatory cells soakage were observed by microscopic analysis within liver tissues. Moreover, NO production was also increased by BCG or/and CM stimuli in the culture supernatant, and a lot of iNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of GLP significantly mitigated hepatic tumefaction, decreased ALT enzyme release and NO production in serum/supernatant, improved the pathological changes of chronic and acute inflammation induced by BCG-stimuli in mice. Moreover, the immunohistochemical result showed that GLP inhibited iNOS protein expression in BCG-immune hepatic damage model.

CONCLUSION: The present study indicates that NO participates in immune liver injury induced by Mycobacterium bovis BCG infection. The mechanisms of protective roles by GLP for BCG-induced immune liver injury may be due to influence NO production in mice.

Keywords: $[Keywords]