title: Metabolic changes in the mouse kidney after subcutaneous injection of butyl 2-chloroethyl sulfide.
abstract: Subcutaneous exposure to vesicants such as butyl 2-chloroethyl sulfide (butyl mustard, BCS) produces local tissue injury (vesication) primarily by alkylation and cross-linking of the purine nucleotides and rapidly binding to proteins. We recently reported that administering BCS can cause other biochemical and morphological alterations, not only in tissues at the injection site but in other areas as well. In this study, we have examined the metabolic effects of BCS administration on the mouse kidney. At 1, 24, and 48 h after injection (5 microliters neat, sc), treated mice were terminated along with an untreated control group, and the kidneys were analyzed for metabolic changes. Glutathione (GSH) peroxidase (GPx) activity markedly increased, (+78 and +85%), but NADP-dependent isocitrate dehydrogenase activity decreased (-43 and -37%) at 1 and 24 h, respectively. Glucose-6-phosphate dehydrogenase (G6PD) remained unchanged at 1 and 24 h, but increased 20% (p less than .05) at 48 h after injection. Kidney glutathione S-transferase (GST) was increased at 24 h after injection. Both total and oxidized GSH levels were significantly lower than control values (approximately 30%) at all time points. Lipid peroxidation, as estimated by the thiobarbituric (TBA) acid-reactive products, was 45% lower (p less than .05) after 1 h. Kidney GPx, G6PD, and GT activities and kidney GSH levels were consistent with changes associated with oxidative stress or detoxication mechanism for BCS. The decrease in TBA-reactive products suggests that mouse kidney metabolic response to BCS injection was different from responses observed for other organs (eyes, brain, and lung).
authors.affiliation: Letterman Army Institute of Research, Presidio of San Francisco, California.
authors.forename: S T
authors.initials: ST
authors.lastname: Omaye
authors.forename: N M
authors.initials: NM
authors.lastname: Elsayed
authors.forename: G J
authors.initials: GJ
authors.lastname: Klain
authors.forename: D W
authors.initials: DW
authors.lastname: Korte
mesh_terms: D000818:Animals; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D007279:Injections, Subcutaneous; D007521:Isocitrate Dehydrogenase / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009151:Mustard Gas / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity* / Q000031:analogs & derivatives
chemical_list: C061448:2-chloroethyl butyl sulfide; D007521:Isocitrate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D009151:Mustard Gas; D019803:Glutathione Disulfide