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

Overview

Journal J Clin Biochem Nutr

Specialty Biochemistry

Date 2017 Jun 7

PMID 28584400

Citations 3

Authors

Yosihiji Ohta

Koji Yashiro

Koji Ohashi

Yosuke Horikoshi

Chiaki Kusumoto

Tatsuya Matsura

Affiliations

Soon will be listed here.

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 glycogenolysis and lipid peroxidation through neutrophil infiltration following mast cell degranulation in rat livers.

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