L-mimosine 对 Wistar 大鼠的产前毒性。

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Toxicon Pub Date : 2025-01-01 DOI:10.1016/j.toxicon.2024.108223
Elaine R.M. de Almeida , Silvana L. Górniak , Cláudia Momo , Vinicius L.S. Ferreira , Edimar C. Pereira , Isis M. Hueza
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引用次数: 0

摘要

l -蜜胺是银合欢(Leucaena leucocephala)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,使其成为潜在的药理学靶点,尽管它也会导致毒性。本研究旨在探讨左旋蜜胺经胎盘传代及其对胚胎发育的影响。妊娠Wistar大鼠分为对照组(CO2;n=8或CO3;n=6,根据实验设计2或3),仅接受载体,并接受剂量为60 (n=9), 100 (n=8), 140 (n=9)和240 (n=7) mg/kg的l -氨基糖胺组从妊娠日(GD) 6至19。为了进行胎盘移植分析,使用5只大鼠:2只作为对照,3只在GD12至gd14期间用140mg/kg的l -氨基糖胺治疗。所有的动物都免费得到食物和水。分析的参数为体重增加;水和食物消耗;血清生化;血细胞计数;生育指标;以及胎儿的组织病理学,内脏和骨骼分析。剂量为60mg /kg、100mg /kg和140mg/kg的组中,细胞的变化(P
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Prenatal toxicity of L-mimosine in Wistar rats
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.
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来源期刊
Toxicon
Toxicon 医学-毒理学
CiteScore
4.80
自引率
10.70%
发文量
358
审稿时长
68 days
期刊介绍: Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.
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