Effect of repeated administration of hexabromobenzene and 1,2,4,5-tetrabromobenzene on the levels of selected cytochromes in rat liver.
OBJECTIVE
Hexabromobenzene (HBB) is a flame retardant, which added to polymers, plastics, textiles, wood or paper, decreases the amount of carbon monoxide and heat release during fire. HBB is also formed as a result of decabromodiphenyl oxide pyrolysis or natural decabromobiphenyl ether debromination as the effect of photolysis. 1,2,4,5-Tetrabromobenzene (1,2,4,5-tetraBB) is a compound formed in the body as a metabolite of HBB. Both these compounds may appear in the environment and human tissue. The purpose of the study was to estimate the effect of repeated administration of HBB and 1,2,4,5-tetraBB on the levels of selected cytochromes in rat liver.


METHODS
The investigated compounds were administered intragastrically in three different doses for 7, 14, 21 or 28 days. Relative liver mass was estimated as well as total concentration of cytochromes P-450 and EROD (CYP 1A) and PROD (CYP 2B) activity in rat liver. Concentration of cytochromes P-450 was determined in microsomal fraction (using the spectrometric method). EROD and PROD were detected by fluorimetric method.


RESULTS
Repeated administration of 1,2,4,5-tetraBB and HBB (in the highest dose) was found to increase relative liver mass. After 1,2,4,5-tetraBB administration, total liver concentration of cytochromes P-450 increased even by several times, depending on the volume and number of doses. Less pronounced alterations were found after repeated administration of HBB. Exposure to HBB resulted in a tenfold increase in EROD activity (after 14-28 days) and a significantly lower increase in PROD activity. 1,2,4,5-TetraBB increased EROD activity by 2-3 times and PROD activity by maximum 2 times.


CONCLUSIONS
Following the experiments, it may be stated that HBB and 1,2,4,5-tetraBB are inductors of microsomal enzymes system. 1,2,4,5-TetraBB more than HBB increases the level of total concentration of cytochromes and induces isoform CYP 2B (PROD). Administration of HBB resulted in the increase in CYP 1A (EROD) activity comparable to that after 3-methylcholanthrene.
Bruchajzer
Elzbieta
E
Department of Toxicology, Faculty of Pharmacy, Medical University, Lódź, Poland. ebruchajzer@pharm.am.lodz.pl
Frydrych
Barbara
B
Szymańska
Jadwiga A
JA
D000818:Animals; D001969:Bromobenzenes / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001969:Bromobenzenes; D005411:Flame Retardants; C110818:1,2,4,5-tetrabromobenzene; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; C017363:hexabromobenzene