Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice.
Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
Developmental Research Department, Sanwa Kagaku Kenkyusho Co., Ltd, Mie, Japan.
S
S
Yokochi
Y
Y
Ishiwata
H
H
Hashimoto
F
F
Ninomiya
T
T
Suzuki
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001219:Aspartate Aminotransferases / Q000097:blood; D018845:CD11 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003354:Corynebacterium Infections / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005857:Germanium; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000276:immunology; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011422:Propionates; D011425:Propionibacterium acnes
D000907:Antibodies, Bacterial; D018845:CD11 Antigens; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D011422:Propionates; D005857:Germanium; D018664:Interleukin-12; C066750:propagermanium; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase