Monochloramine produces reactive oxygen species in liver by converting xanthine dehydrogenase into xanthine oxidase

Journal Article · Tue Sep 15 04:00:00 EDT 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.06.006· OSTI ID:21272652

Sakuma, Satoru ^[1]; Miyoshi, Emi; Sadatoku, Namiko; Fujita, Junko; Negoro, Miki ^[1]; Arakawa, Yukio ^[2]; Fujimoto, Yohko ^[1]

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1. Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)
2. Clinical Laboratory of Practical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

In the present study, we assessed the influence of monochloramine (NH{sub 2}Cl) on the conversion of xanthine dehydrogenase (XD) into xanthine oxidase (XO) in rat liver in vitro. When incubated with the partially purified cytosolic fraction from rat liver, NH{sub 2}Cl (2.5-20 {mu}M) dose-dependently enhanced XO activity concomitant with a decrease in XD activity, implying that NH{sub 2}Cl can convert XD into the reactive oxygen species (ROS) producing form XO. The NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion in the rat liver cytosol was completely inhibited when added in combination with an inhibitor of NH{sub 2}Cl methionine (25 {mu}M). A sulfhydryl reducing agent, dithiothreitol at concentrations of 0.1, 1 and 5 mM also dose-dependently reversed the NH{sub 2}Cl (5 {mu}M)-induced XD/XO interconversion. These imply that NH{sub 2}Cl itself acts on the XD/XO interconversion, and that this conversion occurs at the cysteine residues in XD. Furthermore, using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate, it was found that NH{sub 2}Cl could increase ROS generation in the cytoplasm of rat primary hepatocyte cultures, and that this increase might be reversed by an XO inhibitor, allopurinol. These results suggest that NH{sub 2}Cl has the potential to convert XD into XO in the liver, which in turn may induce the ROS generation in this region.

• OSTI ID: 21272652
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 239; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CYSTEINE
CYTOPLASM
DOSES
IN VITRO
INJURIES
LIVER
METHIONINE
OXIDASES
RATS
REDUCING AGENTS