Ethyl gallate, a scavenger of hydrogen peroxide that inhibits lysozyme-induced hydrogen peroxide signaling in vitro, reverses hypotension in canine septic shock.
Although hydrogen peroxide (H2O2) is a well-described reactive oxygen species that is known for its cytotoxic effects and associated tissue injury, H2O2 has recently been established as an important signaling molecule. We previously demonstrated that lysozyme (Lzm-S), a mediator of sepsis that is released from leukocytes, could produce vasodilation in a phenylephrine-constricted carotid artery preparation by H2O2 signaling. We found that Lzm-S could intrinsically generate H2O2 and that this generation activated H2O2-dependent pathways. In the present study, we used this carotid artery preparation as a bioassay to define those antioxidants that could inhibit Lzm-S's vasodilatory effect. We then determined whether this antioxidant could reverse the hypotension that developed in an Escherichia coli bacteremic model. Of the many antioxidants tested, we found that ethyl gallate (EG), a nonflavonoid phenolic compound, was favorable in inhibiting Lzm-S-induced vasodilation. In our E. coli model, we found that EG reversed the hypotension that developed in this model and attenuated end-organ dysfunction. By fluorometric H2O2 assay and electrochemical probe techniques, we showed that EG could scavenge H2O2 and that it could reduce H2O2 production in model systems. These results show that EG, an antioxidant that was found to scavenge H2O2 in vitro, was able to attenuate cardiovascular dysfunction in a canine in vivo preparation. Antioxidants such as EG may be useful in the treatment of hemodynamic deterioration in septic shock.
Health Sciences Centre, GF-221, 820 Sherbrook St., Winnipeg, MB R3A 1R9, Canada. minksn@cc.umanitoba.ca
Steven N
SN
Mink
Hans
H
Jacobs
Jose
J
Gotes
Krika
K
Kasian
Zhao-Qin
ZQ
Cheng
D000818:Animals; D004285:Dogs; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D066298:In Vitro Techniques; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D016166:Free Radical Scavengers; C048734:ethyl gallate; D005707:Gallic Acid; D006861:Hydrogen Peroxide; D009113:Muramidase