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Butylated hydroxyanisole inhibits tumor necrosis factor‐induced cytotoxicity and arachidonic acid release
Author(s) -
Brekke OleLars,
Espevik Terje,
Bjerve Kristian S.
Publication year - 1994
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02537148
Subject(s) - butylated hydroxyanisole , cytotoxicity , butylated hydroxytoluene , tbars , phospholipase a2 , arachidonic acid , chemistry , antioxidant , biochemistry , tumor necrosis factor alpha , pharmacology , biology , endocrinology , enzyme , in vitro , lipid peroxidation
The mechanisms by which the antioxidant butylated hydroxyanisole (BHA) inhibits recombinant tumor necrosis factor alpha (rTNF‐α)‐induced cytotoxicity have been studied in WEHI 164 clone 13 (WEHI) and L929 fibrosarcoma cells. When BHA was added simultaneously with rTNF‐α, it completely inhibited rTNF‐α cytotoxicity in the WEHI and L929 cells. BHA also inhibited the toxicity when added 2 h after rTNF‐α in WEHI cells, suggesting that BHA inhibits some late intracellular event(s) in rTNF‐α cytotoxicity. Pretreating WEHI cells with BHA for 4 h did not decrease the binding of rTNF‐α to its receptors as measured using flow cytometry. BHA inhibited rTNF‐α 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‐α‐induced cytotoxicity nor the rTNF‐α‐induced release of [ 3 H]arachidonic acid. By comparison, BHA completely inhibited the rTNF‐α‐induced release of arachidonic acid, suggesting that BHA somehow inhibits rTNF‐α‐induced activation of phospholipase(s). In WEHI cells, rTNF‐α increased the level of protein‐associated thiobarbituric acid reactive substances (TBARS) dose‐dependently. BHA, but not BHT, blocked rTNF‐α‐induced cytotoxicity and rTNF‐α‐induced accumulation of protein‐associated TBARS, suggesting that rTNF‐α cytotoxicity is correlated with protein‐associated TBARS. In conclusion, the results suggest that BHA blocks some post receptor event in rTNF‐α‐induced cytotoxicity, and that activation of phospholipase(s) coupled with the enzymatic formation of specific oxidized lipids could be a pivotal event in rTNF‐α‐induced cytotoxicity.