No contribution to lipopolysaccharide-induced hepatic damage in galactosamine-sensitized mice

Fusako Takayama, Toru Egashira, Yasumitsu Yamanaka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

To investigate the role of nitric oxide (NO) in hepatitis-induced endotoxemia, we injected mice intraperitoneally with 250 mg/kg galactosamine (GalN) and 1 mg/kg lipopolysaccharide (LPS) separately and in combination. NO synthesis increased in a dose-dependent manner with LPS. NO generation at 5 hr after administration of LPS was greater than that at 24 hr. Enhancement of NO generation was demonstrated in mice administered GalN and LPS in combination. A nitrosyl-heme signal in 10,000 g supernatant of liver homogenate, due to cytochrome P450 (P450) combining with NO, NO-P450, was detected at more than ten hr and even more after administration of LPS by electron spin resonance (ESR) measurements at 77°K. The strongest NO-P450 signal and most extreme elevation of aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum and of lysosomal enzyme activity in plasma were observed in the GalN+LPS group. Their potency was greater than in the 10 mg/kg LPS group, which was even greater than in the LPS 1 mg/kg group. The aniline hydroxylase activity was inversely proportional to NO-P450 signal intensity. It appears that NO might contribute to LPS-induced hepatic damage in GalN-sensitized mice through degeneration and inactivation of liver microsomal enzymes by binding P450 active sites.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalJournal of Toxicological Sciences
Volume24
Issue number1
Publication statusPublished - Feb 1999
Externally publishedYes

Fingerprint

Galactosamine
Lipopolysaccharides
Nitric Oxide
Liver
Ketoglutaric Acids
Transaminases
Cytochrome P-450 Enzyme System
Aniline Hydroxylase
Endotoxemia
Electron Spin Resonance Spectroscopy
Enzyme activity
Aspartate Aminotransferases
Alanine Transaminase
Heme
L-Lactate Dehydrogenase
Aspartic Acid
Alanine
Hepatitis
Paramagnetic resonance
Catalytic Domain

Keywords

  • Cytochrome P450
  • Detoxification
  • Electron spin resonance
  • Galactosamine-sensitized LPS-treated
  • Nitrosyl-heme complex
  • NO

ASJC Scopus subject areas

  • Toxicology

Cite this

No contribution to lipopolysaccharide-induced hepatic damage in galactosamine-sensitized mice. / Takayama, Fusako; Egashira, Toru; Yamanaka, Yasumitsu.

In: Journal of Toxicological Sciences, Vol. 24, No. 1, 02.1999, p. 69-75.

Research output: Contribution to journalArticle

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