Toxicity And Mechanism Of Experimental Intrauterine Growth Retardation Induced By Tobacco And Alcohol And Effects Of Sodium Ferulate On It

Intrauterine Growth Retardation (IUGR) is a major cause of perinatal morbidity and mortality. There are many factors that influence fetal growth including maternal, fetal and placental factors. It is essential to establish an experimental IUGR model in animals for further study of this disease.The central nervous system develops rapidly during pregnancy and is particularly vulnerable to external influences. When xenobiotics are administrated during the critical period of the brain, the developing neurons are affected directly, of which the amount are determinate before birth and thus influence the postnatal intelligence and behavior. Evaluation of the neurobehavioral development of the offspring includes development of neonatal reflexes such as surface righting reflex, negative geotaxis reflex and cliff avoidance reflex and behavioral alterations in adulthood such as motor-coordination and abilities of learning and memory.Angelica is one of the important ingredients of many effective Chinese herbal prescriptions in preventing and treating IUGR and Sodium ferulate (SF) is the effective monomer of it. However, it is not known whether SF itself is effective of IUGR.Our study observed the long-term neurobehavioral alterations in IUGR mice offspring on the basis of an experimental IUGR model in animals successfully induced by the combination of tobacco and alcohol exposure and explore the relationship between neurobehavioral development and antioxidative functions of the body. We further observed the therapeutic effect of SF on IUGR and speculate this might due to its increasing effects on the antioxidative functions of the placental.OBJECTIVE: To determine whether in utero tobacco and alcohol exposure induces long-term neurobehavioral alterations and whether oxidative stress/damage is a possible causal factor. And to investigate the effects of SF and its possible mechanism on experimental IUGR in rats. METHODS: Gravid mice were subjected to tobacco smoking and alcohol consumption. Their offspring were subsequently evaluated in developmental,and behavioral tests. Antioxidative enzymes and erythrocyte membrane fluidity of adult offspring were measured, regnant Sprague-Dawley rats were divided into 5 groups as follows: normal control group, IUGR control group, SF 25, 50 mg ?kg"1 groups, and salvia miltirrhiza positive control (SM) group. IUGR model was produced by passive smoking and alcohol drinking. From pregnant day 7 till parturition, SF group were given 25 and 50 mg 'kg'1 'd'1 of SF by gavages, respectively. SM group were given SM injection 5 g 'kg "d"1 intragastrically. Others were given an equivalent volume of distilled water. Parameters of fetal development including body weight, body length, body length and weight of organs were measured. The pathological changes of placentas were examined. Placental Antioxidative enzymes were assayed. RESULTS: The intrauterine tobacco and alcohol exposure has resulted in significant reduced postnatal body and organ weights accompanied by reduced gestational body weight gain in their mothers. Such exposure also induced remarkable developmental delay in neonatal reflexes and notable behavioral deficit in adulthood, namely reduced motive coordination and locomotor activity as well as impaired learning and memory abilities. Furthermore, the formation of malondialdehyde (MDA) increased significantly whereas the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (Cat) and glutathione S-transferases (GST) decreased in the cerebral cortex and liver of prenatal intoxicated offspring. The embryonic intoxication also markedly reduced erythrocyte membrane fluidity in offspring. The contents of MDA and GSH were higher in IUGR group than those in control group (P<0.05). Meanwhile, the activities of SOD and Cat were lower in IUGR group than those in the control (P<0.01, P<0.05). These indexes were adjusted by SF or SM injection adminstration, and fetal development parameters in treated group are near to those in the normal control. The pathological c...