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

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  • Ohta Yosihiji
    Department of Chemistry, Fujita Health University School of Medicine
  • Yashiro Koji
    Department of Chemistry, Fujita Health University School of Medicine
  • Ohashi Koji
    Department of Clinical Biochemistry, Faculty of Medical Chemistry, Fujita Health University School of Health Sciences
  • Horikoshi Yosuke
    Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Totorri University Faculty of Medicine
  • Kusumoto Chiaki
    Department of Gastroenterology, Nippon Kokan Fukuyama Hospital
  • Matsura Tatsuya
    Division of Medical Biochemistry, Department of Pathophysiological and Therapeutic Science, Totorri University Faculty of Medicine

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Abstract

<p>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 glycogenolysis and lipid peroxidation through neutrophil infiltration following mast cell degranulation in rat livers.</p>

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