Response of mouse brain to a single subcutaneous injection of the monofunctional sulfur mustard, butyl 2-chloroethyl sulfide (BCS)*.
Exposure to mustard-type vesicants results in alkylation of DNA and vesication. However, the biochemical mechanism for vesicant injury and whether it is localized or diffuse are not clear. We postulated that vesicant damage is mediated by free radicals, resulting in oxidative stress. These free radicals-mediated reactions may propagate systemically distal to the site of exposure. To test this hypothesis, we examined the effects of a single subcutaneous injection of the monofunctional sulfur mustard, butyl 2-chloroethyl sulfide (BCS), on the brain. We injected 3 groups (6 mice/group) of 5-month-old male, athymic, nude mice, weighing 30-35 g, subcutaneously with neat (undiluted) BCS (5 microliters/mouse). After 1, 24, and 48 h, we sacrificed the treated mice along with an untreated control group and analyzed the brains for biochemical markers of oxidative stress. Compared to untreated controls, the activity of glutathione peroxidase increased by 76%, P less than 0.005 at 24 h, and that of glutathione S-transferases by 25-37%, P less than 0.05 over the entire period. Total glutathione content in the brain was significantly lower, 17%, after 1 h and 23% after 24 h. We found also, concomitant with decreased glutathione, almost a 3-fold increase in susceptibility to lipid peroxidation. Because these changes are consistent with oxidative stress, we conclude that the effect of BCS administered subcutaneously may be translocated, reaching mouse brain, and causing oxidative stress.
Elsayed
N M
NM
Letterman Army Institute of Research, Presidio of San Francisco, CA 94129.
Omaye
S T
ST
Klain
G J
GJ
Inase
J L
JL
Dahlberg
E T
ET
Wheeler
C R
CR
Korte
D W
DW
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007279:Injections, Subcutaneous; D008054:Lipid Peroxides / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009150:Mustard Compounds / Q000633:toxicity*; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity* / Q000031:analogs & derivatives; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D013997:Time Factors
D008054:Lipid Peroxides; D009150:Mustard Compounds; C061448:2-chloroethyl butyl sulfide; D009249:NADP; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D009151:Mustard Gas