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

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 (approximately 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 trans-plancental 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.

Evaluation of turmeric (Curcuma longa) effect on biochemical and pathological parameters of liver and kidney in chicken aflatoxicosis

“…The reason of elevation in hepatic enzyme activities (ALT and AST) in chickens receiving aflatoxin could be the hepatic damage and leakage of enzymes in the bloodstream. Similar data have been reported previously (Fatemi et al, 2006;Hashem & Mohamed, 2009;Quezada et al, 2002). Although in the present study, a diet containing 3 ppm aflatoxin significantly increased serum AST and ALT but this finding is in contrast to the finding of Huff et al (1992) that has reported aflatoxin caused a decrease in the activity of AST.…”

Meta-analytical study of productive and nutritional interactions of mycotoxins in growing pigs

“…These links represent the primary biochemical lesion produced by aflatoxins and determine the reduction in protein biosynthesis and, consequently, in the animal growth. Conversely, aflatoxin-epoxide can also be connected with glutathione, constituting an important way of detoxification of this composite (Fatemi et al, 2006). However, the level of glutathione in the cells is dependent on the availability of cysteine, an amino acid partially formed by methionine.…”

Chemopreventive effects of caraway powder and oils to suppress 1, 2- dimethylhydrazine-induced colon carcinogenesis

“…Increase in CYP450 activity in DMH-treated rats confirming its role in detoxification of DMH as a carcinogen [6][7][8][9]. Also, induction of GST activity, one of the main biotransformation enzymes in phase II detoxification pathway, in liver of DMH treated rats may be due to its effective role in detoxification of carcinogenic metabolite of DMH [10,45]. In this connection, caraway seeds as well as oils decrease the hepatic CYP450 elevated in DMH treated rats.…”