International Research Journal of Natural Sciences Vol.2, No.1, pp.1-20, March 2014 Published by European Centre for Research Training and Development UK (www.ea-journals.org) 1 LACTATING PTU EXPOSURE: II- ALTERS THYROID-AXIS AND PROOXIDANT- ANTIOXIDANT BALANCE IN NEONATAL CEREBELLUM R.G. Ahmed a* , A.W. El-Gareib b , S. Incerpi c a Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni- Suef University, Beni-Suef, Egypt b Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt c Department of Sciences, University of Roma Tre, Viale G. Marconi, 446, 00146 Roma, Italy Corresponding author: R.G. Ahmed; Tel/Fax numbers: +02-010-9147-1828 ABSTRACT: The aim of the present study was to evaluate the effect of lactating 6-propyl-2- thiouracil (PTU) on the interactions between the thyroid-axis and prooxidant/antioxidant markers in neonates. PTU was administered to female rats in drinking water (0.1% w/v) from birth to lactation day (LD) 30. The administration gave rise to a highly significant decrease in serum thyroxine (T4) and triiodothyronine (T3) levels and increase in serum thyrotropin (TSH) level in both dams and their offspring at LDs 20 and 30 relative to control group. Also, in PTU group, a marked depression was observed in serum of neonatal growth hormone (GH). In this hypothyroid state, obvious elevation of oxidative markers (protein carbonyls, lipid peroxidation, NO and H 2 O 2 ) was observed at postnatal days (PNDs) 20 and 30, along with decreased activities of antioxidants markers (total thiol, glutathione, glutathione peroxidase, superoxide dismutase and catalase) in neonatal cerebellum with respect to control group. Also, the administration caused some histopathological changes in neonatal cerebellar cortex, such as oedema, vacuoles, reduction of the Purkinje cells, and cellular fragmentations at PND 30. Thus, hypothyroidism in lactating PTU impairs the neonatal neuroendocrine system via production of free radicals, and this, may cause damage of proteins and lipids at the plasma membrane and cellular components delaying cerebellum development. KEYWORDS: 6-propyl-2-thiouracil, Thyroid, Cerebellum, Antioxidants, Prooxidant, Rat newborns INTRODUCTION In the last fifteen years, an increasing number of studies have indicated that THs have important physiological functions, not only during brain maturation (Ahmed and Incerpi, 2013) but also in the adult vertebrate brain (Broedel et al., 2003; Horn and Heuer, 2010). THs are known to set the cellular basal metabolic rate and are considered as major regulators of energy metabolism; mitochondrial activity and biogenesis; oxygen consumption and active oxygen metabolism (Martinez et al., 2001; Bhanja and Chainy, 2010). Thus, one of the most important functions performed by THs is the tight regulation of cellular oxygen consumption and consequent generation of reactive oxygen species (ROS) in several tissues (Mircescu, 2008; Petrulea et al.,