Hence, in the last few decades, considerable attention has been drawn to functional teratology, an extension beyond the investigation of morphological examinations to include the evaluations of

functional integrity of organ systems. In this work we have proposed an evaluation of the functional integrity in organs system of mothers and their offspring by redox evaluation of several enzymatic and non-enzymatic parameters. The redox profile is important because ROS are generated in cells by several pathways and there has been much speculation regarding the role of free radicals during development (Allen and Balin, 1989 and Hitchler and Domann, 2007). According to the free radical theory of development, it is the influence of the balance between the production and removal BYL719 mw of ROS/RNS (Hitchler and Domann, 2007). We show in the present work, for the first time, vitamin A supplementation at 2500, 12,500 and 25,000 IU/kg/day during pregnancy and nursing to rats inducing a prooxidant state in maternal and offspring hippocampus and striatum. In addition, SGI-1776 behavioral alterations were also observed in the homing and open field tests.

These doses were used in order to evaluate the effects of equivalent doses to those stated as safe for humans during pregnancy and breastfeeding upon dams and their offspring. Additionally, the doses investigated Clomifene in this work are all lower than 163,000 IU/kg/day, the lowest observed adverse effect level (LOAEL) of retinyl palmitate in rats, established in segment II developmental toxicity testing (Ritchie et al., 1998). The brain

is sensitive to oxidative stress due to its high content of peroxidizable fatty acids and relative decreased antioxidant defenses (Halliwell and Gutteridge, 1999). Clearly, in maternal striatum and hippocampus, lipid peroxidation occurred when dams received retinyl palmitate supplementation. In addition, protein carbonylation also increased in these maternal tissues and was present at lower doses then lipid peroxidation, as did decreased protein thiol content in the hippocampus. These molecular changes could indicate an increased vulnerability of nigral proteins to the oxidative insult induced in this experimental model. In offspring striatum and hippocampus, retinyl palmitate supplementation also increased lipid peroxidation and protein carbonylation; however, reduced thiol content was found only in male offspring striatum. Increased lipoperoxidation, protein carbonylation levels, and decreased total thiol content make it easier for intra- and inter-molecular cross-links of proteins, which in turn induce conformational changes leading to increased hydrophobicity and aggregation (Goetz and Gerlach, 2004).