Comparative study on the toxicity of methyl linoleate-9,10-ozonide and cumene hydroperoxide to alveolar macrophages.
In the present study the in vitro toxicities of methyl linoleate-9,10-ozonide (MLO) and cumene hydroperoxide (CumOOH), a model peroxidative agent, are compared. This was carried out using the inhibition of alveolar macrophage phagocytosis as an assessment of in vitro toxicity. Both agents, MLO and CumOOH caused a dose-dependent decrease in the phagocytosing activity of alveolar macrophages isolated from rat lungs. MLO was found to be three times more toxic than CumOOH. Supplementation of macrophages with vitamin C resulted in a decrease of their sensitivity towards MLO and an increase of their sensitivity towards CumOOH, suggesting that different mechanisms underlie the toxic effects of the compounds concerned. This was supported by the data on GSH and vitamin E depletion. In both cases, depletion of the antioxidant was more extensive on exposure to CumOOH. In addition, following GSH depletion, the sensitivity of the macrophages towards CumOOH was more increased than towards MLO. Further, MLO was not able to enhance the peroxide formation from methyl linoleate (ML), whereas CumOOH initiated the peroxide formation of ML. The results of ESR spin trap experiments further supported that MLO-induced toxicity is independent of lipid peroxidation. From all this it is concluded that both mechanisms known to be of importance for peroxide-induced cell toxicity, i.e., depletion of cellular GSH levels and/or lipid peroxidation are not the main processes causing MLO toxicity in vitro.
Hempenius
R A
RA
Dept. of Toxicology, Agricultural University, Wageningen, The Netherlands.
Rietjens
I M
IM
Grooten
H N
HN
de Vries
J
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001555:Benzene Derivatives / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000138:chemical synthesis / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000975:Antioxidants; D001555:Benzene Derivatives; D005609:Free Radicals; D008041:Linoleic Acids; C052559:methyl linoleate ozonide; C007164:cumene hydroperoxide