Abstract:
:Aflatoxin B1(AFB1)-glutathione(GSH) conjugation is the major pathway for the detoxification of aflatoxin metabolites. This reaction is catalysed by GSH S-transferase (GST) and play a major role in modulation of AFB1 adduct formation to nuclear DNA. Changes recorded in hepatic GST activity during development of rats can alter the balance between AFB1-GSH conjugation and AFB1-DNA adduct formation. Measurment of cytosolic GST using 1-chloro-2,4-dinitrobenzene (CDNB) as the substrate showed that the enzyme activity is initially lower in weanling tissues as compared to that of adults. But nevertheless hepatic and renal cytosolic GST activity is increased significantly in growing rats pretreated with AFB1. Kinetic studies of AFB1-GSH conjugate formation in kidneys and livers of the two-age groups of rats treated with a single i.p. dose of AFB1 (400 microg/kg b.w.) revealed that at the end of 24 h of AFB1 administration the rate of the conjugate formation in kidneys of immature rats was approximately twice of that measured in adults. Age-related differences in the GST activity as well as AFB1-GSH conjugation was more pronounced in kidneys. The conjugate formation in kidneys of growing rats during 6-24 h following AFB1 administration shows that urinary excretion of aflatoxin metabolites is relatively rapid in growing rats. The major portion of the AFB1-GSH is formed in liver but contribution of the renal tissue to the formation of detoxification metabolites can not be ruled out. These data demonstrate that aflatoxin metabolites are eliminated more efficiently from kidneys of a growing rat. AFB1-induced GST induction in renal tissues of growing animals during 24 h of the carcinogen administration could be considered as an important mechanism for GSH conjugate formation and aflatoxin detoxification. Therefore GST induction in response to hepatotoxic drugs can confer resistance to young animals being exposed for the first time to such drugs. It is also worthmentioning that the GST activity measured before AFB1 administration does not reflect the rate of AFB1 detoxification via GSH conjugation.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Allameh A,Farahani M,Zarghi Adoi
10.1016/s0047-6374(00)00105-6subject
Has Abstractpub_date
2000-05-18 00:00:00pages
73-83issue
1-2eissn
0047-6374issn
1872-6216pii
S0047-6374(00)00105-6journal_volume
115pub_type
杂志文章abstract::This paper presents evidence derived from the selective use of codons in ca. 40 eukaryotic genes (or messages derived from them) that codon usage is one of the most conserved features of messages for specific cell products. The theory has been developed by several investigations that the kinds of products of many if n...
journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
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journal_title:Mechanisms of ageing and development
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更新日期:2002-11-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(83)90072-6
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(83)90051-9
更新日期:1983-03-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(00)00169-x
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2006.09.002
更新日期:2006-12-01 00:00:00