Butylated hydroxyanisole inhibits tumor necrosis factor-induced cytotoxicity and arachidonic acid release.
Lipids
; 29(2): 91-102, 1994 Feb.
Article
em En
| MEDLINE
| ID: mdl-8152351
ABSTRACT
The mechanisms by which the antioxidant butylated hydroxyanisole (BHA) inhibits recombinant tumor necrosis factor alpha (rTNF-alpha)-induced cytotoxicity have been studied in WEHI 164 clone 13 (WEHI) and L929 fibrosarcoma cells. When BHA was added simultaneously with rTNF-alpha, it completely inhibited rTNF-alpha cytotoxicity in the WEHI and L929 cells. BHA also inhibited the toxicity when added 2 h after rTNF-alpha in WEHI cells, suggesting that BHA inhibits some late intracellular event(s) in rTNF-alpha cytotoxicity. Pretreating WEHI cells with BHA for 4 h did not decrease the binding of rTNF-alpha to its receptors as measured using flow cytometry. BHA inhibited rTNF-alpha toxicity in the presence of actinomycin D and cycloheximide, indicating that neither mRNA nor protein synthesis is necessary for the BHA effect. The antioxidant butylated hydroxytoluene (BHT) and indomethacin did not inhibit the rTNF-alpha-induced cytotoxicity nor the rTNF-alpha-induced release of [3H]arachidonic acid. By comparison, BHA completely inhibited the rTNF-alpha-induced release of arachidonic acid, suggesting that BHA somehow inhibits rTNF-alpha-induced activation of phospholipase(s). In WEHI cells, rTNF-alpha increased the level of protein-associated thiobarbituric acid reactive substances (TBARS) dose-dependently. BHA, but not BHT, blocked rTNF-alpha-induced cytotoxicity and rTNF-alpha-induced accumulation of protein-associated TBARS, suggesting that rTNF-alpha cytotoxicity is correlated with protein-associated TBARS. In conclusion, the results suggest that BHA blocks some post receptor event in rTNF-alpha-induced cytotoxicity, and that activation of phospholipase(s) coupled with the enzymatic formation of specific oxidized lipids could be a pivotal event in rTNF-alpha-induced cytotoxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hidroxianisol Butilado
/
Sobrevivência Celular
/
Fator de Necrose Tumoral alfa
/
Ácido Araquidônico
Limite:
Animals
Idioma:
En
Revista:
Lipids
Ano de publicação:
1994
Tipo de documento:
Article