de Almeida Elaine R M, Górniak Silvana L, Momo Cláudia, Ferreira Vinicius L S, Pereira Edimar C, Hueza Isis M
Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, S.P., Brazil.
Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo (ICAQF-UNIFESP), Diadema, S.P., Brazil.
Toxicon. 2025 Jan;254:108223. doi: 10.1016/j.toxicon.2024.108223. Epub 2024 Dec 30.
L-Mimosine is the main active component of the plant Leucaena leucocephala. Due to its metal-chelating mechanism, it interacts with various metabolic pathways in living organisms, making it a potential pharmacological target, although it also leads to toxicity. The present study aimed to investigate the transplacental passage of L-mimosine and its effects on embryofetal development. Pregnant Wistar rats were divided into control groups (CO2; n = 8 or CO3; n = 6, according to experimental design 2 or 3) that received only the vehicle, and groups that received doses of 60 (n = 9), 100 (n = 8), 140 (n = 9), and 240 (n = 7) mg/kg of L-mimosine from gestational day (GD) 6-19. For the transplacental analysis, five rats were used: two as controls and three treated with a dose of 140 mg/kg L-mimosine from GD12 to 14. All the animals received food and water ad libitum. The parameters analyzed were body weight gain; water and food consumption; serum biochemistry; blood cell counts; reproductive indices; and histopathological, visceral and skeletal analyses of the fetuses. In the groups that received doses of 60, 100, and 140 mg/kg, alterations (P < 0.05) in the skeletal development of the fetuses were observed. In the 240 mg/kg group, a decrease (P < 0.05) in total food consumption; a decrease (P < 0.05) in absolute leukocyte and neutrophil counts; alterations (P < 0.05) in the levels of ALT, GGT, and creatinine enzymes; a decrease (P < 0.05) in the relative weight of the thymus along with a loss of the corticomedullary distinction; coalescence of lymphoid follicles in the spleen; and skeletal and visceral alterations and alopecia were observed. L-Mimosine was detected in the amniotic fluid of the rats. These results demonstrate the complex action of L-mimosine, leading to toxic effects on both dams and fetuses, highlighting the risk of exposure to this substance during the perinatal period, which negatively impacts embryo/fetal and neonatal growth and development.
L-含羞草碱是银合欢植物的主要活性成分。由于其金属螯合机制,它与生物体中的各种代谢途径相互作用,使其成为一个潜在的药理学靶点,尽管它也会导致毒性。本研究旨在调查L-含羞草碱的胎盘转运及其对胚胎发育的影响。将怀孕的Wistar大鼠分为对照组(根据实验设计2或3,CO2组n = 8或CO3组n = 6),仅接受赋形剂,以及从妊娠第6天至19天接受60(n = 9)、100(n = 8)、140(n = 9)和240(n = 7)mg/kg L-含羞草碱剂量的组。为了进行胎盘分析,使用了5只大鼠:2只为对照组,3只从妊娠第12天至14天接受140 mg/kg L-含羞草碱剂量的处理。所有动物均可自由获取食物和水。分析的参数包括体重增加;水和食物消耗;血清生化指标;血细胞计数;生殖指标;以及胎儿的组织病理学、内脏和骨骼分析。在接受60、100和140 mg/kg剂量的组中,观察到胎儿骨骼发育有改变(P < 0.05)。在240 mg/kg组中,总食物消耗量减少(P < 0.05);绝对白细胞和中性粒细胞计数减少(P < 0.05);ALT、GGT和肌酐酶水平有改变(P < 0.05);胸腺相对重量减少(P < 0.05),同时皮质髓质分界消失;脾脏中淋巴滤泡融合;观察到骨骼和内脏改变以及脱发。在大鼠的羊水中检测到了L-含羞草碱。这些结果表明L-含羞草碱具有复杂的作用,对母鼠和胎儿均产生毒性作用,突出了围产期接触该物质的风险,这对胚胎/胎儿和新生儿的生长发育产生负面影响。