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Azathioprine hepatotoxicity and the protective effect of liquorice and glycyrrhizic acid
Author(s) -
Wu YueTing,
Shen Chong,
Yin Jian,
Yu Jinpeng,
Meng Qin
Publication year - 2006
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.1920
Subject(s) - azathioprine , glutathione , pharmacology , intracellular , viability assay , chemistry , antioxidant , in vitro , biochemistry , medicine , pathology , enzyme , disease
This study aimed to evaluate the responses of human hepatocytes to azathioprine hepatotoxicity in comparison with the well‐studied azathioprine hepatotoxicity in rat hepatocytes and the effects of protective agents to suppress azathioprine hepatotoxicity. Azathioprine presented its hepatotoxicity at clinically relevant concentrations (lower than 10 µ m ) in primary rat hepatocytes after 48 h of treatment as shown by a severe decrease in cell viability as well as intracellular GSH depletion. However, primary human hepatocytes exhibited only significant intracellular GSH depletion after treatment with azathioprine at these clinically relevant concentrations, while a reduction in cell viability by 29% was only evidenced after 48 h of treatment with azathioprine at the high concentration of 50 µ m . In addition, a monolayer culture of primary rat hepatocytes was used as an in vitro model to examine the protective effects of antihepatotoxic drugs including glutathione (GSH), N‐acetylcysteine (NAC, a GSH precursor), liquorice and glycyrrhizic acid (GA), a major bioactive component of liquorice, against hepatotoxicity of 1 µ m azathioprine. It was found that both liquorice and GA showed substantial protection according to assays of cell viability and intracellular GSH, while neither GSH nor NAC had such a protective function. Similarly, GA protected human hepatocytes from intracellular GSH depletion on exposure to 1 µ m azathioprine. These results implied that GA or liquorice could be considered as potent protection agents against azathioprine hepatotoxicity. Copyright © 2006 John Wiley & Sons, Ltd.