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Alpha-lipoic acid ameliorates cytarabine-induced developmental anomalies in rat fetus
Human & Experimental Toxicology ( IF 2.7 ) Pub Date : 2020-11-23 , DOI: 10.1177/0960327120975114
Ramanachary Namoju 1, 2 , Naga Kavitha Chilaka 1
Affiliation  

Cytarabine (Ara-C) is a nucleoside analogue used in the treatment of cancers and viral infections. It has teratogenic potential and causes a variety of birth defects in fetuses. Alpha-lipoic acid (ALA) is a natural antioxidant offers protection against the developmental toxicity induced by drug- or toxicant-exposure or pathological conditions. This study was aimed at evaluating the protective effect of ALA against Ara-C induced developmental toxicity in rat fetus. Pregnant rats divided into five groups and received normal saline, ALA200 mg/kg, Ara-C12.5 mg/kg, Ara-C25 mg/kg and, Ara-C25 mg/kg plus ALA200 mg/kg respectively from gestational day (GD) 8 to GD14 and sacrificed on GD21. Ara-C treatment led to a significant and dose-dependent decrease in food intake, weight gain, placental weight, and an increase in oxidative stress in pregnant rats. Further, the in-utero exposure to Ara-C led to an increase in fetal mortality, resorptions, oxidative stress, external morphological anomalies and limb abnormalities, and impaired ossification. Co-administration of ALA resulted in amelioration of the footprints of Ara-C induced toxicity in pregnant rats as well as the fetus. These findings indicate that the ALA supplementation offers protection against developmental toxicity caused by Ara-C prenatal exposure in rats.



中文翻译:

α-硫辛酸改善阿糖胞苷诱导的大鼠胎儿发育异常

阿糖胞苷 (Ara-C) 是一种核苷类似物,用于治疗癌症和病毒感染。它具有致畸潜力,会导致胎儿出现多种先天缺陷。α-硫辛酸 (ALA) 是一种天然抗氧化剂,可针对药物或毒物暴露或病理条件引起的发育毒性提供保护。本研究旨在评估 ALA 对 Ara-C 诱导的大鼠胎儿发育毒性的保护作用。妊娠大鼠分为五组,从妊娠日(GD ) 8 到 GD14 并在 GD21 上牺牲。Ara-C 治疗导致怀孕大鼠食物摄入量、体重增加、胎盘重量和氧化应激增加的显着和剂量依赖性减少。此外,子宫内暴露于 Ara-C 导致胎儿死亡率、吸收、氧化应激、外部形态异常和肢体异常以及骨化受损的增加。ALA 的共同给药导致妊娠大鼠和胎儿中 Ara-C 诱导的毒性足迹的改善。这些发现表明,ALA 补充剂可防止大鼠产前暴露于 Ara-C 引起的发育毒性。

更新日期:2020-11-25
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