Department of Clinical Biochemistry, School of Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
Int J Dev Neurosci. 2023 Nov;83(7):615-630. doi: 10.1002/jdn.10289. Epub 2023 Aug 15.
The present study aimed to analyse both neurobehavioural and biochemical results of neonates born of mothers exposed to different doses of lithium along with the groups that received lithium at the highest dose with folic acid as a preventive treatment.
Male and female rats were mated in separate cages, and pregnant rats were divided into eight first group as (1) vehicle; (2) propylthiouracil (PTU)-induced hypothyroidism; (3-4) received two different doses of lithium carbonate (15 and 30 mg/kg); (5-7) the highest doses of lithium (30 mg/kg) plus three different doses of folic acid (5, 10 and 15 mg/kg); and (8) received just folic acid (15 mg/kg). All treatments were dissolved in drinking water and continued until delivery, followed by returning to a regular diet without treatment.
Lithium (30 mg/kg) disrupts both behavioural and biochemical markers, including TSH, T3 and T4 as measuring indicators to assess thyroid function, IL-10 and TNF-α as anti-inflammatory and inflammatory agents, respectively, malondialdehyde as an oxidative stress marker, alongside SOD, and catalase activity as antioxidant indicators. Besides, folic acid, almost at the highest dose (15 mg/kg), attenuated memory impairement and anxiety-like behaviour caused by lithium. Moreover, the groups treated with folic acid alone in comparison with vehicles demonstrated higher levels of antioxidant and anti-inflammatory indicators.
According to the results, prenatal exposure to a high dose of lithium (30 mg/kg) leads to foetal neurodevelopmental disorder and growth restriction through various mechanisms more likely attributed to hypothyroidism, which means it should be either prohibited or prescribed cautiously during pregnancy.
本研究旨在分析母亲暴露于不同剂量锂盐的新生儿的神经行为学和生化结果，以及接受最高剂量锂盐并作为预防治疗的叶酸的各组的结果。
雄性和雌性大鼠在单独的笼子中交配，妊娠大鼠分为八组：（1）对照组；（2）丙硫氧嘧啶（PTU）诱导的甲状腺功能减退症组；（3-4）分别接受两种不同剂量的碳酸锂（15 和 30mg/kg）；（5-7）最高剂量的锂（30mg/kg）加三种不同剂量的叶酸（5、10 和 15mg/kg）；（8）仅接受叶酸（15mg/kg）。所有治疗均溶解在饮用水中，持续至分娩，然后恢复常规饮食，不再治疗。
锂（30mg/kg）破坏了行为和生化标志物，包括 TSH、T3 和 T4 作为评估甲状腺功能的指标，IL-10 和 TNF-α 作为抗炎和炎症标志物，丙二醛作为氧化应激标志物，以及 SOD 和过氧化氢酶活性作为抗氧化标志物。此外，叶酸（15mg/kg）几乎在最高剂量下可减轻锂引起的记忆损伤和焦虑样行为。此外，与对照组相比，单独接受叶酸治疗的各组显示出更高水平的抗氧化和抗炎指标。
根据研究结果，产前暴露于高剂量锂（30mg/kg）通过多种机制导致胎儿神经发育障碍和生长受限，这些机制更可能归因于甲状腺功能减退症，这意味着在怀孕期间应禁止或谨慎使用锂。
