Differential antioxidant enzyme activities and glutathione content betweenrat and rabbit conceptuses

Redox status regulates numerous cellular processes like transcription facto r activation and binding, protein folding, and calcium sequestration. Becau se 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 t he redox status of two species that have demonstrated differential sensitiv ity to teratogens represents a novel approach for determining the role of r edox alteration in teratogenesis. Furthermore, examining specific regions o f the embryo may also help to explain why certain tissues are uniquely sens itive, while others are resistant to oxidative insult. In the presented stu dy, 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 w as dissected into three portions-the limbs, the head, and the trunk. Sample s were placed in the appropriate buffers for the measurement of both direct and indirect redox status contributors-GSH, cysteine, thioredoxin, glutath ione disulfide, protein-glutathione mixed disulfides, superoxide dismutase, glutathione peroxidase, and glutathione disulfide reductase. Species compa rison 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 be cause it is inherently more pro-oxidizing and may be more easily perturbed resulting in misregulation of cellular processes. Differences were most app arent in the limb as compared to the embryonic head and trunk, where the ra bbit 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 regulati on of biochemical and molecular events that may be associated with mechanis ms of teratogenesis. These may contribute to a more complete rationale for choosing a species for study and provide a better correlation with human de velopmental toxicants. (C) 2001 Elsevier Science Inc.