Maternal Nicotine Exposure and Carbohydrate Metabolism of Fetal and Neonatal Lung Tissue: Response to Nicotine Withdrawal

Abstract

The metabolic response of fetal and neonatal lung tissue to maternal nicotine exposure (0.25 and 1.0 mg/kg body weight/day) was investigated. White virgin female rats (Wistar) of 200–250 g were used. The rats were mated overnight and were afterwards randomly assigned to control and experimental groups. The experimental group was subdivided into two groups. One group received nicotine during pregnancy and lactation. The second group received nicotine only during lactation. The suckling rats were killed 24 h after the last dose of nicotine was administered to the mother. The lung tissue was surgically removed and the in vitro utilization of exogenous glucose and endogenous glycogen determined. Lactate production was also determined to assess glycolytic activity. Maternal nicotine administration during pregnancy and lactation stimulated total glucose turnover by 21.6 and 86.4% respectively but suppressed glycogenolysis (32.7%) and glycolysis by 24.6% (p < 0.01). Nicotine administration during lactation only enhanced total glucose turnover by 19.1% (p < 0.01) and glycogenolysis by 30% (p < 0.01) but inhibited glycolysis by 25.8%. After 4 weeks of nicotine withdrawal when the rats were 7 weeks old, glycogenolysis and glycolysis of those animals exposed to nicotine via the placenta and mother’s milk were still inhibited to the same extent as during exposure. Glycogenolysis and the glycolytic flux of lung tissue of rats exposed to nicotine via mother’s milk only returned to normal. Since rat lung tissue has reached maturation at this stage, it is conceivable to assume that exposure to nicotine during pregnancy will have a permanent adverse effect on carbohydrate metabolism in lung tissue and thus on the aspects of lung development and differentiation dependent on these pathways.

Nicotine and lung development

“…1) in lung tissue of the rat fetus and neonate (Maritz, 1986(Maritz, , 1987. The lower glycogenolytic activity is due to a lower phosphorylase activity in the lungs of the nicotine exposed offspring (Maritz, 1986).…”

“…In addition to the reduced flux of glucose through the glycolytic pathway (Maritz, 1987), cAMP also accumulates in the lungs of the nicotine exposed rat pups. Furthermore, the cAMP content of the lungs of the nicotine exposed offspring increased even after nicotine withdrawal (Maritz and Burger, 1992).…”

Effect of Smoking on Maternal Glucose Metabolism

“…On a cellular level, enzyme induction by nico tine may result in a higher glucose-6-phosphate dehydro genase activity and increased glycolysis [5].…”

“…Since nicotine does affect glucose metabolism in ani mal studies [5] the negative effect of smoking on fetal growth could to some extent be mediated by a change in glucose metabolism in the mother.…”

Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring

“…It also reduces the antioxidant capacity of the lungs [Hussain et al 2001;Maritz, 1993]. Since oxidants [Kalpana and Menon, 2004] and nicotine [Kleinsasser et al 2005] can induce point mutations in DNA (Figure 2), it is possible that the imbalance in the oxidant/antioxidant status of the developing lung, resulted in the altered 'programming' and consequently the lower glycolytic capacity of the lungs of the rats that were exposed to nicotine during gestation and lactation [Maritz, 1987] as well as the drastic increase in AMP [Maritz and Burger, 1992]. This theory is supported by the observation that maternal vitamin C supplementation during gestation and lactation prevented the lowering of the glycolytic capacity of the lungs of the offspring [Maritz, 1993] as well as the development of microscopic emphysema ( Figure 5).…”