托皮拉对正常肝脏和脂肪肝的影响
Sevtap Kılınç1, Pelin Şahin2, Zeynep Yığman3,4
1Department of Physiology, Faculty of Medicine, Başkent University, Ankara, Turkey.
Drug and chemical toxicology
|November 3, 2023
概括
托皮拉胺 (TPM) 降低体重和葡萄糖,但增加氧化应激和肝损伤,特别是在非酒精性脂肪肝疾病 (NAFLD) 模型中. 需要仔细考虑使用TPM的肝病患者.
科学领域:
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
- 生物化学 生化学
背景情况:
- 托皮拉胺 (TPM) 是一种碳酸酶 (CA) 抑制剂,因其抗肥胖性质而闻名.
- 非酒精性脂肪性肝病 (NAFLD) 影响了绝大多数肥胖个体.
- 在脂肪肝状况下,TPM对氧化剂-抗氧化剂参数和CA活性的影响在很大程度上仍未被探索.
研究的目的:
- 在非酒精性脂肪性肝病 (NAFLD) 的老鼠模型中研究托皮拉胺 (TPM) 对氧化剂-抗氧化剂状态和碳酸酶 (CA) 活性的影响.
- 评估TPM在饮食引起的肥胖和NAFLD的背景下潜在的肝保护性或肝毒性作用.
主要方法:
- 维斯塔尔白性老鼠被分为四组:对照组,TPM组,高脂肪饮食 (Diet组) 和饮食+TPM组.
- 在21天的时间里,TPM被用100毫克/公斤/天给相关组.
- 生物化学测定 (MDA,GSH,GPx,CA活性) 和组织学分析在肝脏组织上进行.
主要成果:
- 服用TPM可以抵消体重增加和高脂肪饮食引起的血糖水平升高.
- 在所有组中,TPM显著降低了CA活动.
- TPM治疗导致恶性甲酸 (MDA) 增加,谷氨 (GSH) 和谷氨过氧化酶 (GPx) 水平降低,这表明氧化应激.
- 组织学检查显示肝损伤,包括透,乙素和细胞质真空化,特别是在TPM和饮食+TPM组.
- 在饮食诱导的组中,NAFLD和相关得分升高,在饮食+TPM组中,特征恶化.
结论:
- 托皮拉 (TPM) 可以诱导氧化应激和肝损伤,这种影响在患有饮食诱导的非酒精性脂肪性肝病 (NAFLD) 的老鼠中得到放大.
- 观察到的碳酸 anhydrase (CA) 活性下降与MDA负相关,与GSH水平正相关.
- 强烈建议在给诊断为肝病,特别是NAFLD的患者开处方TPM时谨慎.
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