乙甲在雌性鼠中的剂量依赖性肝毒性
Mehmet Cihan Yavaş1, Gül Şahika Gökdemir2, Kübra Tuğçe Kalkan3
1Department of Biophysics, Faculty of Medicine, Mardin Artuklu University, 47200 Mardin, Turkey.
Toxics
|February 26, 2026
概括
暴露于甲基甲酸 (DEP) 在大鼠中会导致严重的肝损伤,包括炎症和DNA损伤,即使肝酶水平正常. 这凸显了超越标准测试进行全面评估的必要性.
科学领域:
- 毒理学 毒理学 毒理学
- 环境健康 环境健康
- 肝病学 肝病学是一种肝病学.
背景情况:
- 酸盐是广泛使用的增塑剂,环境和健康问题越来越严重.
- 甲基甲酸 (DEP) 是一种常见的甲酸,需要对其生物效应进行研究.
研究的目的:
- 研究亚急性口服暴露于甲基乙甲酸盐 (DEP) 对大鼠肝脏组织和功能的剂量依赖性影响.
- 为了评估DEP暴露后肝脏的组织病理,生化,炎症和遗传毒性变化.
主要方法:
- 在21天的时间内,对雌性Wistar白化老鼠进行DAP (100,300,600毫克/公斤) 的口服服.
- 对血清生物化学参数,肝脏组织病理学 (H&E,马森三色),免疫组织化学 (IL-1β,TGF-β),组织ELISA (IL-6,TNF-α) 和对DNA损伤的彗星测定进行分析.
主要成果:
- DEP诱导了显著的,剂量依赖的肝细胞病理变化,包括和真空化.
- 观察到AST水平升高,并增加了促炎性细胞因子 (IL-6,TNF-α,IL-1β) 和TGF-β的表达.
- 在肝脏组织中检测到显著的DNA损伤,表明基因毒性.
结论:
- 在小鼠中,低急性DEP暴露会导致严重的肝炎,组织病理学变化和基因毒性.
- 仅仅血清肝酶可能无法充分反映DEP诱导的肝损伤的全部程度.
- 综合评估对于了解DEP对肝脏健康的毒理影响至关重要.
相关概念视频
Toxicity Testing in Animals
63
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
63
Drug Toxicity: Dose-Dependent Reactions
54
Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
54
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
314
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
314
Drug Toxicity: Risk factors
59
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
59


