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Changes in hepatic cytosolic glutathione S-transferase activity and expression of its class-P during prenatal and postnatal period in rats treated with aflatoxin B1

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Abstract

The effect of aflatoxin B1 (AFB1) on the expression of glutathione S-transferase-P (GST-P) which is the major isoform of GST in developmental stages has been investigated in rat liver during prenatal and postnatal stages. Following administration of AFB1 (0, 0.5, 1.0, 2.0, 3.0 or 4.0 mg/kg bw) injected I.P on day 8.5 of gestation the number of dead or reabsorbed fetuses and malformed embryos were recorded. Then the fetal livers were processed for measurement of total GST and GST-P activities, using 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (ETA) as substrates respectively. RT-PCR using rat GST-P specific primers was performed on mRNA extracted from livers. Besides, the effects of AFB1 on hepatic GST and GST-P were assessed in groups of suckling rats directly injected with the toxin. The results show that a single dose of AFB1 (1.0 or 2.0 mg/kg bw) caused approximately 50–60% depletion in fetal liver GST towards CDNB. Postnatal experiments revealed that liver GST (using CDNB as substrate) was significantly induced (~40%) in suckling rats injected with a single dose of AFB1 (3.0 mg AFB1/kg) 24 h before killing. Liver GST-P expression was unaffected due to AFB1 exposures of rats before and after the birth. This finding was substantiated by western blotting and RT-PCR techniques. These data suggest that AFB1-related induction in rat liver total GST after birth may be implicated in protective mechanisms against AFB1. In contrast, inhibition of this enzyme in fetal liver following placental transfer of the carcinogen may explain high susceptibility of fetal cells to transplancental aflatoxins. Furthermore, lack of influence of AFB1 on GST-P expression in developmental stages can role out the involvement of this class of GST in AFB1 biotransformation.

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Authors and Affiliations

  1. Department of Biochemistry Faculty of Medical Science, Tarbiat Modarres University, P.O. Box 14115-331, Tehran, Iran

    Faezeh Fatemi, Abdolamir Allameh, Abolfazl Dadkhah, Somayeh Kazemnejad & Roya Sharifi

  2. Department of Biotechnology Faculty of Medical Science, Tarbiat Modarres University, P.O. Box 14115-331, Tehran, Iran

    Mehdi Forouzandeh

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  1. Faezeh Fatemi
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  2. Abdolamir Allameh
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  3. Abolfazl Dadkhah
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  4. Mehdi Forouzandeh
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  5. Somayeh Kazemnejad
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Correspondence to Abdolamir Allameh.

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Fatemi, F., Allameh, A., Dadkhah, A. et al. Changes in hepatic cytosolic glutathione S-transferase activity and expression of its class-P during prenatal and postnatal period in rats treated with aflatoxin B1. Arch Toxicol 80, 572–579 (2006). https://doi.org/10.1007/s00204-006-0076-2

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