Effects Of Maternal Nicotine Exposure Research Articles

Postnatal effects of maternal nicotine exposure on the striatal dopaminergic system in rats

The biochemical effects of continuous prenatal exposure to nicotine (1.5 mg kg-1 day-1) have been examined in 14 day old male and female rat pups. The ability of striatal tissue slices from the nicotine-exposed pups to synthesize [3H]dopamine from [3H]tyrosine was enhanced. However, the ability of (+)-amphetamine to stimulate formation and release of [3H]dopamine from [3H]tyrosine was not affected. Furthermore, prenatal exposure to nicotine increased the rate of striatal dopamine turnover in the male, but not the female nicotine-exposed pups.

Effect of maternal nicotine exposure on neonatal rat lung development: protective effect of maternal ascorbic acid supplementation

ABSTRACTIn previous studies it was shown that maternal nicotine exposure during pregnancy and lactation interfered with fetal and neonatal lung growth and development. It was suggested that the adverse effects of maternal nicotine exposure on the lungs of the offspring may be due to inadequate protection of these lungs against oxidants. Wistar rats were used in this study. After mating the rats were randomly assigned into 4 groups, namely a control group, a group receiving only nicotine, a group exposed to only vitamin C, and a group exposed to both nicotine and vitamin C. The aim of this study was, firstly, to determine the effect of maternal nicotine exposure (1 mg/kg body weight/day, subcutaneously) during gestation and lactation on the lungs of the offspring; secondly, to test whether the subcutaneous administration of vitamin C (0.5 mg/kg body weight/day) influences lung development; and, lastly, to determine whether subcutaneous administration of vitamin C will prevent the adverse effects of maternal nicotine exposure on lung development in the offspring. Morphologic and morphometric techniques were used to determine the effect of nicotine and vitamin C on lung development in the offspring on postnatal days 14, 21, and 42. The results showed that maternal exposure to nicotine only or vitamin C only resulted in a gradual deterioration of the parenchyma of the lungs of the offspring. These changes, which resembled microscopic emphysema, only became evident after the lungs of the offspring reached maturation. Those animals that were exposed to both nicotine and vitamin C via the placenta and mother's milk were less severely affected. It is also not advisable to use subcutaneous administration of vitamin C during gestation and lactation to prevent smoke- and nicotine-related effects on the developing lung, and other strategies should be investigated.

Effects of Maternal Nicotine Exposure on Expression of Collagen Type IV and its Roles on Pulmonary Bronchogenesis and Alveolarization in Newborn Mice.

Nicotine is one the chemical substance with high level of toxically. It crosses the placenta and accumulates in the developing organs of fetus. Our previous investigations indicated that collagen type IV plays a key role in basement membrane of various embryonic organs. In this study we evaluated the effect of maternal nicotine exposure pre and postnatal period on collagen IV expression during bronchogenesis and alveolarization in the lungs of newborn mice. Female Balb/C mice were mated and Sperm positive in vaginal smear was designated as embryonic day zero. Pregnant mice were divided into 2 experimental and 2 control groups. Experimental group 1, received 3 mg/kg nicotine intrapritoneally from day 5 of gestation to last day of pregnancy. Experimental group 2 received the same amount of nicotine during the same gestational days as well as 2 first week after birth (lactation). The control groups received the same volume of normal saline during the same periods. At the end of exposure times, all of newborns were anesthetized and their lungs were removed for immunohistochemical method. Our finding indicated that collagen reaction in the bronchial basement membrane and extra cellular matrix of lung parenchyma in experimental groups increased significantly compared to control groups. Our results also showed alveolar remodeling and abnormal bronchogenesis were observed in experimental group especially group 2. These data indicate that maternal nicotine exposure may induce abnormal collagen IV expression and cause defects in bronchopulmonary development.

Neonatal nicotine exposure alters leptin signaling in the hypothalamus–pituitary–thyroid axis in the late postnatal period and adulthood in rats

Aims Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus–pituitary–thyroid axis of suckling and adult offspring. Main methods Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14 days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p < 0.05. Key findings In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+ 58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (−61%, −42%, −56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (−52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (−44%, −50%, −47%) and higher pSTAT-3 expression (+ 80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+ 1.54x) and lower pSTAT-3 content (−34%). Significance Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.

Indicators of oxidative stress in weanling and pubertal rats following exposure to nicotine via milk

Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for infant and children diseases. It is concentrated in breast milk and is absorbed by the infant. The purpose of the present study was to investigate the effects of maternal nicotine exposure during lactation on breast-fed rats and at the pubertal age by measuring biomarkers of oxidative stress. Particularly, a new parameter, the thiol concentration was evaluated. Two groups of lactating Wistar rats were used. For the first group, female rats were given an intraperitoenal injection of nicotine or saline (2 mg/kg per day) during lactation. For the second group, we reproduced the same process described above and then the female and male pups were separately kept after weaning without any treatment until the puberty (at 45 days of age). In the liver and lung of the offspring, we examined the malondialdehyde (MDA) level, the thiol concentration, and the activities of two antioxidant enzymes: superoxyde dismutase (SOD) and catalase (CAT). In the plasma, alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were measured. For rats aged 21 days, the treatment significantly reduced the thiol concentration, SOD, and CAT activities but increased MDA level, AST, and ALT activities. For rats aged 45 days, the males and females did not react the same way. In fact, the males were more affected. These results indicate that maternal nicotine exposure during the lactation period induces oxidative stress in the liver and lung of lactating offspring, which is maintained until the puberty, especially for the male rats.

Short- and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile, and thyroid function of rat offspring

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor.

Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats

The present study determined the effect of maternal nicotine exposure during the early developmental period on AT 1R and AT 2R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg/kg/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine treatment. Nicotine significantly increased brain AT 1R in fetuses at gestation 15 and 21 days and decreased central AT 2R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT 1R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT 2R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT 1R mRNA abundance did not change during postnatal development, AT 2R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT 1R mRNA in the female offspring. In contrast, it decreased AT 2R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT 1R/AT 2R mRNA ratio in the brain of adult animals, which was significantly up-regulated in nicotine-treated animals with females being more prominent than males. The results demonstrate that perinatal nicotine exposure alters AT 1R and AT 2R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.

Influence of maternal nicotine exposure on neonatal rat oxidant–antioxidant system and effect of ascorbic acid supplementation

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. We aimed to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on oxidant-antioxidant system, and to determine a protective effect of ascorbic acid (Asc). Gravid rats were assigned into four groups. In Group 1, pregnant rats received 6-mg/kg/day nicotine subcutaneously during pregnancy from 1 to 21 days of gestation and lactation (until postnatal day 21). Group 2 received nicotine and Asc for the same period. In Group 3, the rats received nicotine during lactation. Control pregnant rats (Group 4) received only saline subcutaneously. Serum malondialdehyde (MDA), myeloperoxidase (MPO), and superoxide dismutase (SOD) levels were determined at 21 days of age. Nicotine exposure decreased birth weight and pregnancy weight gain. MDA values of the rat pups exposed to nicotine in both Groups 1 and 2 were higher than those of control and Group 3. SOD and MPO values of the groups were similar. Mean birth weight and serum MDA levels of Groups 1 and 2 were similar. Nicotine exposure via placental transfer increases oxidative stress as manifested by an increase in MDA level. Asc supplementation does not prevent the adverse effects of maternal nicotine exposure.

Influence of maternal nicotine exposure during gestation and lactation on lactate dehydrogenase isoenzyme profile and transcript levels in developing neonatal rat lung

In this study we investigated the effect of (a) aging on rat lung lactate dehydrogenase (LDH) mRNA expression and isoenzyme profile and, (b) the effect of maternal nicotine exposure during gestation and lactation on LDH isoenzyme profile and mRNA expression in the lungs of the offspring. Pregnant rats were injected subcutaneously (1 mg nicotine/kg body weight/day) from day 1 after mating. Lung tissue to determine LDH isoenzyme profile and mRNA expression was obtained from the offspring. LDH mRNA expression and isoenzyme profile was determined on postnatal days 1, 7, 14, 21 and 49. Generally the %Densities of all the isoenzymes decreased between postnatal days 1 and 49. Between postnatal days 7 and 14, a period associated with rapid alveolar formation, all isoenzymes except LDH-1, decreased ( P < 0.01). During this period all the isoforms in nicotine-exposed lung increased ( P < 0.05). In both control and nicotine-exposed lung LDH-1 is the dominant isoenzyme. The LDH-M and LDH-H isoenzyme levels are higher ( P < 0.001) in the lungs of the nicotine exposed rats. Maternal nicotine exposure during gestation and lactation changed the metabolic status of the nicotine-exposed lungs to become more glycolytic compared to that of the control lung. These changes in LDH isoenzyme profiles and mRNA expression are irreversible.

Influence of maternal nicotine exposure on neonatal rat bone: protective effect of pentoxifylline.

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. The aim of this study was to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on neonatal rat bone development, and to determine a protective effect of pentoxifylline (PTX). Gravid rats were assigned into four groups, one control (group I) and three experimental (groups II, III, and IV). In group II, pregnant rats received 3 mg/kg/day nicotine alone, subcutaneously, until 21 days postnatal. In group III, pregnant rats received nicotine (3 mg/kg/day) and PTX (60 mg/kg/day). In group IV, pregnant rats received PTX alone (60 mg/kg/day). Whole body mineral density (BMD), content (BMC), area (BA), and histopathologic and morphologic findings of the femur were determined at 21 days of age. The study revealed that nicotine exposure (group II) decreased birth weight, pregnancy weight gain, and length of femur compared with other groups (P < 0.01). Birth weight was higher in groups III (PTX + nicotine) and IV (PTX) than in group II (nicotine). Body weight at 21 days of age was higher (P = 0.009) in the PTX alone group (group IV) compared with the other groups. BMD was higher (P < 0.001) in the PTX-treated groups (group III and IV) compared with other groups. In addition, there were more apoptotic chondrocytes in the hypertrophic zone of rats exposed to nicotine alone (group II) compared with the other groups (P < 0.001). In conclusion, maternal nicotine exposure resulted in decreased birth weight, pregnancy weight gain, and bone lengthening, and increased apoptosis. Pentoxifylline supplementation was found to prevent the adverse effects of maternal nicotine exposure on BMD and birth weight.

The Role of Carnosine in Protection Against the Damaging Effect of Maternal Nicotine Exposure During Gestation and Lactation on the Lung of Albino Rat Offspring

The Role of Carnosine in Protection Against the Damaging Effect of Maternal Nicotine Exposure During Gestation and Lactation on the Lung of Albino Rat Offspring

Influence of Maternal Nicotine Exposure on Neonatal Rat Bone: Protective Effect of Ascorbic Acid

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. We aimed to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on neonatal rat bone development, and to determine a protective effect of ascorbic acid. Gravid rats were assigned into three groups: two experimental and one control (group I). In the first experimental group (group II), pregnant rats received 3 mg/kg/d nicotine subcutaneously during pregnancy from 1 to 21 days of gestation and lactation (until postnatal day 21). The second experimental group (group III) received nicotine and ascorbic acid (1 mg/kg body mass/d). Whole body mineral density (BMD), content (BMC), and area (BA) were measured on postnatal day 21. Histopathologic and morphologic findings of the femur were obtained. Maternal nicotine exposure decreased the body weight of the rat at the birth and postnatal day 21. The values of BMD, BA, and BMC of the groups were similar to each other. Width of the epiphyseal plate and the hypertrophic zone were higher in group III but lower in group II than in group I. Number of apoptotic chondrocytes was significantly increased in group II. The length of femur was higher in group I but lower in group II than in group III. Maternal nicotine exposure during gestation and lactation resulted in decreased body weight and bone lengthening. Ascorbic acid supplementation was found to prevent the adverse effects of maternal nicotine exposure on the growth plate.

Effects of Maternal Nicotine Exposure during Lactation on Breast-Fed Rat Pups

Background: Nicotine is known to be associated with adverse effects in infants and children. It is concentrated in breast milk and is absorbed by the infant. The aim of this study was to investigate the effects on breast-fed rat pups of maternal nicotine exposure during lactation. Methods: In the experimental group (n = 6), nicotine was given to lactating dams (2 mg/kg/day) after delivery and continued for 10 days during lactation. Control animals (n = 4) received saline for the same duration. The suckling rats were weighed and killed on postnatal day 10, and samples were taken from the lung, liver, kidney, spleen and small intestine for histopathological examination. Superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were measured in the liver of the dam and the offspring. Results: Histopathological changes in the liver of the nicotine-exposed group showed portal inflammatory infiltrate, ballooning degeneration of hepatocytes, and focal necrosis in the parenchyma. Thickening of alveolar walls because of interstitial inflammation was noted in the lungs. Histopathological examination of kidney, spleen and small intestine tissue did not reveal any abnormality. In the experimental group, SOD and CAT activities were significantly decreased (p <0.001) but MDA levels were significantly increased (p <0.001) compared with the control group. Conclusion: These results indicate that maternal nicotine exposure induces oxidative stress and causes detrimental histopathological changes in the lung and liver of lactating offspring.

Does maternal nicotine exposure during gestation increase the injury severity of small intestine in the newborn rats subjected to experimental necrotizing enterocolitis

Background/Purpose The aim of this study was to evaluate the effects of maternal nicotine exposure during gestation on injury severity of small intestine in the newborn rats subjected to hypoxia-reoxygenation and cold stress. Methods A total of 21 Sprague-Dawley pregnant rats were divided into 3 equal groups. The groups were labeled as group 1, control group; group 2, hypoxia-reoxygenation group; and group 3, nicotine-hypoxia-reoxygenation group. The rats of group 3 were exposed to nicotine via subcuticular injection for the last week of gestation (2 mg/kg/d). Newborn rats were collected immediately after birth to prevent suckling of maternal milk (40 rat pups in group 1, 43 rat pups in group 2, and 41 rat pups in group 3). Litters in groups 2 and 3 were stressed twice daily with asphyxia followed by cold (4°C for 10 minutes) stress to induce hypoxic intestinal injury which is relevant to human necrotizing enterocolitis. Breathing 100% CO 2 for 10 minutes in a chamber followed by 10-minute 100% O 2 breathing was the asphyxia model repeated twice daily. After hypoxia-reoxygenation and cold stress, newborn rats were returned to their mother's cages. This protocol was repeated for the following 2 days, and the rat pups were decapitated on the third day. Using this protocol of asphyxia and cold stress, all of neonatal rats developed clinical and pathological signs of hypoxia-induced intestinal injury. The entire gastrointestinal tract was removed and examined macroscopically. A 2-cm section of distal ileum from each animal was taken for histopathological and biochemical examinations. Histological changes in ileal architecture were scored and graded from 1 to 5. The remaining intestinal tissues of the animals were used for lipid peroxidation analysis. Results Typical signs of hypoxia-induced intestinal injury were observed in the 2 experimental groups (groups 2 and 3) macroscopically. There were more grades 3 and 4 injuries in group 3 ( P < .05). The malondialdehyde levels were elevated in groups 2 and 3 ( P < .001). The malondialdehyde levels of the group 3 were also significantly higher than group 2 ( P < .01). Conclusions Maternal nicotine exposure during gestation results in higher grade histological injury in newborn rats subjected to hypoxia-reoxygenation and cold stress.

Vitamin C Prevents the Effects of Prenatal Nicotine on Pulmonary Function in Newborn Monkeys

Smoking during pregnancy leads to decreased pulmonary function and increased respiratory illness in offspring. Our laboratory has previously demonstrated that many effects of smoking during pregnancy are mediated by nicotine. We now report that vitamin C supplementation can prevent some of the effects of maternal nicotine exposure on pulmonary function of offspring. Timed-pregnant rhesus monkeys were treated with 2 mg/kg/day nicotine bitartrate from Gestation Days 26 to 160. On Gestation Day 160 (term, 165 days) fetuses were delivered by C-section and subjected to pulmonary function testing the following day. Nicotine exposure significantly reduced forced expiratory flows, but supplementation of mothers with 250 mg vitamin C per day prevented the effects of nicotine on expiratory flows. Vitamin C supplementation also prevented the nicotine-induced increases in surfactant apoprotein-B protein. Neither nicotine nor nicotine plus vitamin C significantly affected levels of cortisol or cytokines, which have been shown to affect lung development and surfactant expression. Prenatal nicotine exposure significantly decreased levels of elastin content in the lungs of offspring, and these effects were slightly attenuated by vitamin C. These findings suggest that vitamin C supplementation may potentially be clinically useful to limit the deleterious effects of maternal smoking during pregnancy on offspring's lung function.

Effects of maternal nicotine exposure on lung surfactant system in rats

Maternal smoking during pregnancy may impair pulmonary function in infants and children, but the exact mechanisms underlying these changes remain to be determined. Timed pregnant Sprague-Dawley rats were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from days 3-21 of gestation. A control group was injected with saline. Nicotine-treated dams had lower body weights than control dams from gestational days 5-21, and the values reached statistical significance on gestational days 17, 20, and 21. Total lung saturated phosphatidylcholine contents tended to be lower in nicotine-exposed rats than in control rats from postnatal day 21, and the values reached statistical significance on postnatal days 35 and 42. Maternal nicotine exposure significantly increased surfactant protein (SP)-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 7, and decreased SP-A, SP-B, SP-C, and SP-D mRNA expression on postnatal day 14. In conclusion, maternal nicotine exposure during pregnancy reduces lung surfactant lipids and produces variable changes in surfactant protein gene expression during the late postnatal period. As good surface activity of pulmonary surfactant is essential for normal lung function, these results suggest that derangement of the pulmonary surfactant system may be important in the pathogenesis of impaired pulmonary function in children exposed in utero to nicotine.

POSTNATAL EXPRESSION OF CYTOCHROME P450 1A1, 2A3, AND 2B1 mRNA IN NEONATAL RAT LUNG: INFLUENCE OF MATERNAL NICOTINE EXPOSURE

A critical factor contributing to the etiology or modification of respiratory disease is the ability of the lung tissue to activate or inactivate chemicals. In this study, the authors investigated the effect of maternal nicotine exposure during gestation and lactation on the expression mRNA of cytochrome P450 (CYP) CYP1A1, CYP2A3, and CYP2B1. Fetal rats were exposed to nicotine via maternal administration of nicotine (1 mg/kg body weight/day, subcutaneously); after birth, neonatal rats were exposed to nicotine via the mother's milk. Lung tissue of 1-, 7-, 14-, 21-, and 49-day-old rat pups were used. From weaning on postnatal day 21 up to postnatal day 49, the offspring received no nicotine. Using RNA dot-blot techniques, our results show that CYP mRNA expression in lung tissue increased with age after birth. Maternal nicotine exposure had no influence on CYP1A1 mRNA, but resulted in a marked increase in the expression of CYP2A3 mRNA and CYP2B1 mRNA. The higher levels of CYP2A3 mRNA and CYP2B1 mRNA were maintained after weaning.

Chronic maternal nicotine exposure during gestation and lactation and the development of the lung parenchyma in the offspring: Response to nicotine withdrawal

The aim of this study was to investigate the effect of maternal nicotine exposure during gestation and lactation on: (1) the development of the gas exchange area of the lungs of the offspring; and (2) to determine whether these effects are reversible. Pregnant rats received daily nicotine (subcutaneously 1 mg kg −1 body weight) during gestation and lactation. Nicotine administration started 1 day after mating and lasted until weaning on postnatal day 21. The offspring were exposed to nicotine via the placenta and mother’s milk only. The lung tissue of the neonates was collected on postnatal days 14, 21, 35 and 42 and prepared for morphometry. The results obtained show that maternal nicotine exposure resulted in bigger alveolar volumes and suppressed alveolarisation in the lungs of the offspring. Flattening of the alveoli occurred as the animals aged and as a consequence the internal surface area available for gas exchange decreased; a condition that resembles panlobular emphysema. It is unlikely that these effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring was due to a lower birth weight, or a reduction in the period of gestation, or a poor supply of nutrients to the offspring. The changes in the gas-exchange region of the nicotine-exposed rat pups appear to be irreversible.

IS MATERNAL COPPER SUPPLEMENTATION DURING ALVEOLARIZATION PROTECTING THE DEVELOPING RAT LUNG AGAINST THE ADVERSE EFFECTS OF MATERNAL NICOTINE EXPOSURE? A Morphometric Study

In a previous study, it was shown that maternal nicotine exposure during gestation and lactation interfered with alveolarization and resulted in gradual deterioration of the lung parenchyma, resulting in microscopic emphysema. The aim of this study was thus to investigate the long-term effects of maternal nicotine exposure (1 mg/kg body weight/day, subcutaneous [sc] from the onset of the phase of rapid alveolarization, which occur from postnatal day 4 in rats, on (1) the development of the gas-exchange area of the lungs of the offspring and, (2) whether maternal copper supplementation (1 mg/kg body weight/day, SC) during the same period of time will prevent the effect of maternal nicotine exposure on the development of the neonatal rat lung. Nicotine administration lasted until weaning on postnatal day 21. The day of birth was designated day 0. The offspring were exposed to nicotine via the mother's milk only. The experimental animals received no nicotine or copper after postnatal day 21. The lung tissue of the neonates was collected on postnatal days 14, 21, and 42 and prepared for morphometry. The results obtained show that maternal nicotine exposure had no influence on body weight, chest circumference, crown-rump length, and lung volume, but resulted in bigger alveolar volumes and suppressed alveolarization in the lungs of the offspring. Copper supplementation during this period of lung development reduced the adverse effect of maternal nicotine exposure on neonatal lung development. Even though copper reduced the adverse effects of maternal nicotine exposure during this phase of lung development, it did not prevent the induction of microscopic emphysema.

MATERNAL NICOTINE EXPOSURE DURING PREGNANCY AND LACTATION: I. EFFECT ON GLYCOLYSIS IN THE LUNGS OF THE OFFSPRING

We investigated the effect of maternal nicotine exposure during pregnancy and lactation on carbohydrate metabolism in the neonatal lung. Female rats received nicotine (1 mg/kg body weight/day) subcutaneously from day 7 after mating. Control animals received saline. The suckling rats were killed 24 hours after the last dose of nicotine was administered to the mother on postnatal day 14. The lung tissue of 9 rat pups from 3 litters was surgically removed and the in vitro utilization of exogenous glucose (μmol/g wet lung tissue/h) was determined. Lactate production (μmol/g wet lung tissue/h) was also determined to assess glycolytic activity. Maternal nicotine exposure during pregnancy and lactation stimulated glucose turnover by 21.6% (P<.01), but suppressed glycolysis by 24.6% (P<.001) and glycogenolysis by 37.9% (P<.001). Maternal nicotine exposure during gestation and lactation had no effect on the activity of hexokinase (U/g wet lung tissue), but resulted in a lower phosphofructokinase activity (U/g wet lung tissue) in the lungs of the offspring. From the data, it appeared that the inhibition of the flux of glucose through the glycolytic pathway can be attributed to an inhibition of phosphofructokinase.