左乙拉西坦对大鼠心脏、肝脏和肾脏的致畸作用：光镜、电镜和免疫组织化学研究。
The teratogenic effect of pregabalin on heart, liver and kidney in rats: a light microscopic, electron microscopic and immunohistochemical study.
机构信息
Department of Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
Department of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
出版信息
BMC Pharmacol Toxicol. 2022 Jan 5;23(1):4. doi: 10.1186/s40360-021-00546-2.
BACKGROUND
Pregabalin (PGB) was approved as new anti-epileptic drugs with little information about its teratogenic effect.
AIM OF THE WORK
to evaluate the developmental toxicity of PGB.
MATERIALS AND METHODS
60 pregnant albino rats were divided into three groups. PGB (500 mg/kg body weight/day) was given to group II, PGB (1250 mg/kg body weight/day) was given to Group III and no medications were given to group I. The pups were normally delivered. Liver, kidney and heart specimens were prepared for histological, immunohistochemical, and morphometric studies.
RESULTS
A dose of 500 mg of PGB had minimal toxic effects in the form of mild collagen deposition and moderate positive caspase-3 immunoexpression. PGB dose of 1250 mg/kg induced gross toxic effects in form of degenerated cardiac myofibres, ruptured blood vessels, vacuolations in the renal cortex, fibrosis and strong positive caspase-3 immunoexpression.
CONCLUSION
PGB at dose of 500 mg/kg revealed minimal toxic changes. PGB cause embryotoxicity in a dose-dependent manner, as the higher dose induced more degenerative changes.
背景
普瑞巴林（PGB）作为一种新型抗癫痫药物被批准使用，但关于其致畸作用的信息较少。
目的
评估 PGB 的发育毒性。
材料和方法
将 60 只怀孕的白化大鼠分为三组。第 II 组给予 PGB（500mg/kg 体重/天），第 III 组给予 PGB（1250mg/kg 体重/天），第 I 组给予生理盐水。正常分娩后，取肝脏、肾脏和心脏标本进行组织学、免疫组织化学和形态计量学研究。
结果
500mg PGB 的剂量仅表现出轻微的毒性作用，表现为轻度胶原沉积和中度阳性 caspase-3 免疫表达。1250mg/kg PGB 剂量引起明显的毒性作用，表现为心肌纤维变性、血管破裂、肾皮质空泡化、纤维化和强阳性 caspase-3 免疫表达。
结论
500mg/kg PGB 剂量仅显示出轻微的毒性变化。PGB 呈剂量依赖性诱导胚胎毒性，较高剂量诱导更多的退行性变化。
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