Introduction

The metabolic imbalance of homocysteine (НС) and its accumulation in blood (hyperhomocysteinemia) result in the development of severe pathologies that are accompanied by endothelial dysfunction and blood clottage. An essential aspect of hyperhomocysteinemia is its aggravating effect in pregnancy. Hyperhomocysteinemia is associated with an approximately two to three-fold increased risk for pregnancy-induced hypertension, placenta abruptio, thromboembolic events, neural tube defects and intrauterine growth restriction [1]. Placentation abnormality and placentofetal blood flow disturbance may cause subfertility, e.g. miscarriage and even infertility as a result of implantation defects [2]. Also, hyperhomocysteinemia causes chronic fetoplacental insufficiency and chronic intrauterine hypoxia at the late stage of gestation. This leads to the delivery of infants with low birth weight, and to the depletion of all life-supporting systems functional backup of the new-born, and to the enlargement of a number of complications in the neonatal period.

Hyperhomocysteinemia may be a one cause of generalized microangiopathy at the second half of gestation, which can manifest itself as late toxicosis (gestosis) – nephropathy, preeclampsia and eclampsia [3]. Immature delivery in such cases is accompanied by high infant mortality and a large ratio of neonatal complications.

The infants born by mothers under hyperhomocysteinemia have mental and physical retardation, the mechanisms of which have not been elucidated as yet. Forasmuch as HC is a toxic structural analog of glutamic acid, glutamate receptors are plausible targets for its toxic effect. Under physiological conditions, the HC blood plasma level (as well as its concentration in the brain) is very low; therefore HC cannot compete for ligand-binding sites of the receptors. When the concentration of HC is significantly increased, however, it starts to compete with glutamate for the binding sites, and to hyperactivate subsequent receptors, which causes a number of toxic effects [4].

The most dangerous effect of this competition is the interacting of HC with ionotropic NMDA glutamate receptors, which are involved in the processes of long-term potentiation and are therefore responsible for learning and memorizing, as well as other cognitive functions of the brain. The hyperactivation of the receptors in neurons leads to reactive oxygen species (ROS) accumulation and signal transduction mechanisms disorder [5].

It has been shown recently that carnosine, which is able to regulate the intracellular ROS level and to maintain the viability and functional activity of neurons, can effectively protect neuronal cells from the HC toxic effects [6]. Subsequently, using various cell models (the cerebellum granule cells, neutrophils, and РС-12 pheochromocytoma cells), we showed that the synthetic tripeptide pinealon (Glu-Asp-Arg) could restrict ROS accumulation and prevent apoptosis induced by НС or Н₂О₂; effective pinealon concentrations being much lower than those of carnosine [7].

The aim of this study was to investigate a possible neuroprotective effect of pinealon on the rat offspring developed under conditions of experimental prenatal hyperhomocysteinemia in vivo.