Compound 48/80, a mast cell degranulator, causes oxidative damage by enhancing Vitamin C synthesis via reduced glutathione depletion and lipid peroxidation through neutrophil infiltration in rat livers

Yosihiji Ohta, Koji Yashiro, Koji Ohashi, Yosuke Horikoshi, Chiaki Kusumoto, Tatsuya Matsura

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

In this study, we examined whether compound 48/80 (C48/80), a mast cell degranulator, causes hepatic oxidative damage in rats. Serum and liver biochemical parameters were determined 0.5, 3 or 6 h after a single treatment with C48/80 (0.75 mg/kg). Serum histamine and serotonin levels increased 0.5 h after C48/80 treatment but diminished thereafter. Increases in serum Vitamin C (VC) and transaminases and hepatic hydrogen peroxide, lipid peroxide, and myeloperoxidase levels and a decrease in hepatic reduced glutathione level occurred 0.5 h after C48/80 treatment and further proceeded at 3 h, but these changes diminished at 6 h. Serum lipid peroxide and hepatic VC levels increased 3 h after C48/80 treatment. Hepatic glycogen level decreased 0.5 h after C48/80 treatment and further decreased at 3 h. Pre-administered ketotifen diminished all these changes found at 3 h after treatment, while pre-administered NPC 14686 diminished these changes except changes in serum histamine and serotonin levels. Hepatocellular apoptosis observed at 3 h after C48/80 treatment was attenuated by pre-administered ketotifen and NPC 14686. These results indicate that C48/80 causes oxidative damage by enhancing VC synthesis via reduced glutathione depletion-dependent glycogenosis and lipid peroxidation through neutrophil infiltration following mast cell degranulation in rat livers.

Original languageEnglish
Pages (from-to)187-198
Number of pages12
JournalJournal of Clinical Biochemistry and Nutrition
Volume60
Issue number3
DOIs
Publication statusPublished - 05-2017

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry

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