2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced decrease in the fluidity of rat liver membranes.
1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD)-induced lipid peroxidation has previously been demonstrated by assessing the hepatic content of thiobarbituric acid reactive substances (TBARS) as well as the NADPH-dependent microsomal formation of TBARS as well as the NADPH-dependent microsomal formation of TBARS using malondialdehyde as the standard. 2. Changes in membrane fluidity as a result of lipid peroxidation may occur. Therefore the dose- and time-dependent effects of TCDD on lipid peroxidation in mitochondrial, microsomal, and plasma membranes, and changes in membrane fluidity in these subcellular fractions, were examined. Animals were treated with either 50 or 100 micrograms TCDD/kg orally, and killed 3, 6, or 9 days post-treatment. 3. Time-dependent increases occurred in TBARS content and formation following TCDD administration for all three membranes. Similar results were observed after 50 and 100 micrograms TCDD/kg. 4. Following TCDD administration, fluorescence polarization measurements as determined by the fluorescence polarization (r) and anisotropy parameter (a.p.) values demonstrated significant decreases in membrane fluidity in all membrane fractions, indicative of membrane structural alterations. 5. Excellent inverse correlations between lipid peroxidation and membrane fluidity were observed. Thus, decreased membrane fluidity and increased membrane damage may contribute to the toxic manifestations of TCDD as a consequence of an oxidative stress.
Alsharif
N Z
NZ
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178.
Grandjean
C J
CJ
Murray
W J
WJ
Stohs
S J
SJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013816:Thermodynamics; D013950:Thymus Gland / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D011506:Proteins