Dietary selenium and antioxidant status: toxic effects of 1,2-dimethylhydrazine in rats.
Weanling male Sprague-Dawley rats were used to determine whether the mechanism of the previously reported toxicity of 1,2-dimethylhydrazine (DMH) in selenium-deficient rats was related to a diminished capacity for detoxification of reactive oxygen species via glutathione peroxidase (GSH-Px) as well as by other known pathways of detoxification, including catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and levels of glutathione (GSH). A 3 x 3 factorial experimental design was used to examine the acute effects of DMH treatment (0, 10 and 20 mg/kg body weight) interacting with dietary Se levels (less than 0.02, 0.1 and 0.5 mg/kg diet as sodium selenite). Animals were maintained on the test diets for 4 wk prior to challenge with DMH. Preliminary kinetics studies indicated the most appropriate time to examine antioxidant status was 3 h after DMH injection. At that time, livers and colons were analyzed for tissue levels of GSH-Px, CAT, SOD, GST and GSH. Data analysis demonstrated that Se deficiency impaired the ability of both liver and colon to mount an induced detoxification response to the acute oxidative stress generated by DMH challenge and may explain the toxicity of DMH in Se-deficient rats.
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BC
Department of Pathology, Texas Tech University Health Sciences Center, Lubbock 79430.
D019813:1,2-Dimethylhydrazine; D000818:Animals; D000975:Antioxidants; D002374:Catalase / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D004032:Diet; D004127:Dimethylhydrazines / Q000494:pharmacology / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D004127:Dimethylhydrazines; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione; D012643:Selenium; D019813:1,2-Dimethylhydrazine