The oxidative damage of butenolide to isolated erythrocyte membranes.
Butenolide (CAS No. 16275-44-8), a mycotoxin produced by several Fusarium species, has been shown to be a potential risk factor for animal and human health. This study was undertaken to investigate the potential oxidative damage of butenolide to biomembranes in vitro using the erythrocyte membrane model. Following exposure of isolated rat erythrocyte membranes to butenolide, the extent of oxidative damage was assessed by measuring lipid peroxidation, -SH groups content, Ca2+/Mg2+-ATPase and Na+/K+-ATPase activities, and conformational changes in membrane proteins. It was observed that butenolide resulted in a significant lipid peroxidation, revealed by a concentration-dependent increase in the level of thiobarbituric acid reactive substances (TBARS). Similarly, this toxin induced a concentration-dependent decrease in the content of membrane total -SH groups, as well as free -SH groups. Membrane-bound enzymes were also impaired by the toxin, demonstrated by the marked inhibition of the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase. Conformational changes in membrane proteins were determined using electron paramagnetic resonance (EPR) spin labeling. Butenolide caused an increase in the ratio of weakly to strongly immobilized components (W/S ratio) in a manner of concentration-dependent, indicating conformational changes in membrane proteins occurred. In conclusion, these findings indicate that butenolide is capable of inducing significant oxidative damage to membrane lipids and proteins.
Wang
Yi-Mei
YM
National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, No. 27, Taiping Road, Haidian District, Beijing 100850, PR China.
Peng
Shuang-Qing
SQ
Zhou
Qi
Q
Wang
Min-Wei
MW
Yan
Chang-Hui
CH
Wang
Guo-Qiang
GQ
Yang
Hai-Ying
HY
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000633:toxicity; D000251:Adenosine Triphosphatases / Q000097:blood; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D009183:Mycotoxins; D013113:Spin Labels; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C004511:butenolide; D000251:Adenosine Triphosphatases; D015107:4-Butyrolactone