Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, RJ, Brazil.
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, RJ, Brazil.
Environ Pollut. 2020 Mar;258:113781. doi: 10.1016/j.envpol.2019.113781. Epub 2019 Dec 16.
Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.
哺乳期母体尼古丁暴露会导致雄性成年大鼠肝脏损伤。然而，男性的机制尚不清楚，且尚未对女性进行测试。在此，我们在产后尼古丁暴露模型中，确定了雄性和雌性后代在两个年龄段的肝脏脂质组成和生脂酶。在产后第 2 天（PND2），将渗透压微型泵植入哺乳期 Wistar 大鼠母体中，每天释放 6mg/kg 的尼古丁（NIC 组）或生理盐水（CON 组），持续 14 天。从断奶到安乐死（PND120：1 只幼崽/窝/性别；PND180：2 只幼崽/窝/性别），后代接受标准饮食。在 PND120，与 CON 雄性相比，NIC 雄性的血浆甘油三酯（TG）较低，脂肪变性程度 1 较低，肝胆固醇（CHOL）酯、游离脂肪酸、单酰基甘油含量以及乙酰辅酶 A 羧化酶-1（ACC-1）和脂肪酸合酶（FAS）的肝蛋白表达较高。在这个年龄，与 CON 雌性相比，NIC 雌性的肝细胞结构保存完好，血浆 CHOL 较高，肝 CHOL 酯和总 CHOL 含量较低。在 PND180，NIC 雄性表现出脂肪变性程度 1 和 2，肝 TG 较高，游离脂肪酸和总 CHOL 含量较低，肝 ACC-1 蛋白表达增加。NIC 雌性的血浆 TG 和 CHOL 水平较高，肝形态无变化，肝 CHOL 酯和游离脂肪酸较低，肝总 ACC-1 和 FAS 蛋白表达也较高。母体尼古丁暴露会导致长期的肝功能障碍，肝细胞结构发生改变，且随着雄性年龄的增长而加重。关于雌性，尽管肝细胞结构未改变，但脂质代谢受损，值得进一步关注。
