Carcinogen-induced, free radical-mediated reduction in microsomal membrane fluidity: reversal by indole-3-propionic acid.
Chromium (Cr) is a well established carcinogen, with Cr(III) accounting for much of the intracellular oxidative damage that this transition metal induces. Indole-3-propionic acid (IPA), a melatonin-related molecule, is a reported antioxidant and free radical scavenger. Concentration (1, 10, 100, 500, or 1000 microM) and time (15, 30, 45, 60, or 90 min)-dependent effects of Cr(III) in the presence of H2O2 (0.5 mM), as well as the protective effect of IPA on Cr(III)-induced alterations in membrane fluidity (the inverse of membrane rigidity), as an index of membrane damage, were estimated by fluorescence spectroscopy. Cr(III), in a concentration- and a time-dependent manner, decreased membrane fluidity, with marked effects at a concentration of 500 microM and 60 min of incubation. IPA (5, 3, or 1 mM) prevented the Cr(III)-induced decrease in membrane fluidity. It is concluded that the carcinogen Cr(III), in the presence of H202, generates free radicals, which decrease membrane fluidity in rat microsomal membranes. Membrane alterations are pharmacologically prevented by the antioxidant IPA.
Karbownik
M
M
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, USA.
Garcia
J J
JJ
Lewiński
A
A
Reiter
R J
RJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002857:Chromium / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002273:Carcinogens; D005609:Free Radicals; D007211:Indoles; D002857:Chromium; C015292:indolepropionic acid; D006861:Hydrogen Peroxide