Differential antioxidant enzyme activities and glutathione content between rat and rabbit conceptuses.
Redox status regulates numerous cellular processes like transcription factor activation and binding, protein folding, and calcium sequestration. Because the most abundant reducing equivalent in the cell is glutathione (GSH), it could play a role for teratogens that cause oxidative stress and disrupt pathways involved in differentiation and proliferation. Investigation of the redox status of two species that have demonstrated differential sensitivity to teratogens represents a novel approach for determining the role of redox alteration in teratogenesis. Furthermore, examining specific regions of the embryo may also help to explain why certain tissues are uniquely sensitive, while others are resistant to oxidative insult. In the presented study, New Zealand White rabbit (GD 12) and Sprague Dawley rat embryos (GD 13) were removed from the uterus on days of similar development. Each embryo was dissected into three portions-the limbs, the head, and the trunk. Samples were placed in the appropriate buffers for the measurement of both direct and indirect redox status contributors-GSH, cysteine, thioredoxin, glutathione disulfide, protein-glutathione mixed disulfides, superoxide dismutase, glutathione peroxidase, and glutathione disulfide reductase. Species comparison of whole embryos indicated that the rabbit embryo possesses a higher redox potential (more oxidative) than the rat embryo. Findings, in general, show that the rabbit may be more sensitive to redox-altering teratogens because it is inherently more pro-oxidizing and may be more easily perturbed resulting in misregulation of cellular processes. Differences were most apparent in the limb as compared to the embryonic head and trunk, where the rabbit limb has a significantly more pro-oxidizing redox environment than the rat limb. Species comparisons like these may help in the understanding of how redox shifts affect cellular processes and would contribute to regulation of biochemical and molecular events that may be associated with mechanisms of teratogenesis. These may contribute to a more complete rationale for choosing a species for study and provide a better correlation with human developmental toxicants.
Hansen
J M
JM
Department of Environmental Health Sciences, Toxicology Program, University of Michigan, Ann Arbor, MI, USA.
Choe
H S
HS
Carney
E W
EW
Harris
C
C
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase; D013879:Thioredoxins / Q000378:metabolism
D000975:Antioxidants; D013723:Teratogens; D013879:Thioredoxins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C424443:Txnrd3 protein, mouse; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide