Desferrioxamine-induced alterations in hepatic iron distribution, DNA damage and lipid peroxidation in control and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.
Desferrioxamine (DFX), an iron chelator, has been used to inhibit in vitro redox cycling of the transition iron irons that may interfere with free-radical formation, and is used clinically to treat conditions associated with iron overload. The effect of DFX on hepatic iron distribution has not been examined. Therefore, we have examined the effect of DFX on iron content and distribution, lipid peroxidation and DNA single-strand breaks in liver. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances hepatic lipid peroxidation and induces DNA damage, the ability of DFX to modulate these effects was also examined. Female Sprague-Dawley rats received 200 mg DFX kg-1 i.p. every 12 h for 10 days and 50 micrograms TCDD kg-1 p.o. on Day 4 as a single dose. All animals were killed 7 days after TCDD administration. The results demonstrate that DFX alone did not decrease hepatic iron content, but enhanced the iron distribution in mitochondria, microsomes and nuclei. A 10-day administration of DFX resulted in enhanced hepatic lipid peroxidation and DNA single-strand breaks, consistent with the alterations in iron distribution. TCDD administration produced large increases in lipid peroxidation in microsomes, nuclei and whole-liver homogenates, as well as enhanced DNA damage. However, the marked increases in lipid peroxidation produced by TCDD were attenuated by DFX, while the DNA damaging effects of TCDD and DFX were additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Wahba
Z Z
ZZ
University of Nebraska Medical Center, Omaha.
Murray
W J
WJ
Stohs
S J
SJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003676:Deferoxamine / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000033:anatomy & histology
D000072317:Polychlorinated Dibenzodioxins; D004247:DNA; D007501:Iron; D003676:Deferoxamine