Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice.
We examined whether treatment with amodiaquine, a potent inhibitor of histamine N-methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice, and this improvement was partially associated with the decrease in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment. In conclusion, the present findings suggested that the elevation of endogenous histamine by amodiaquine may thus play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice.
Yokoyama
Akira
A
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Mori
Shuji
S
Takahashi
Hideo K
HK
Kanke
Toru
T
Wake
Hidenori
H
Nishibori
Masahiro
M
D000410:Alanine Transaminase / Q000097:blood; D000655:Amodiaquine / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000655:Amodiaquine; D006632:Histamine; D006637:Histamine N-Methyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase