诺比林对5-甲的肝脏保护作用诱导了肝毒性
Safa A Yahya1, Nada N Al-Shawi1
1University of Baghdad, College of Pharmacy, Department of Pharmacology and Toxicology, Baghdad, Iraq.
Current research in pharmacology and drug discovery
|October 16, 2024
概括
类植物中的一种类黄类物质nobiletin通过减少亡和氧化应激来保护雄性大鼠免受5 - 甲诱导的肝损伤. 这项研究突出了nobiletin的重点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 5-甲 (5-FU) 是一种关键的化疗剂,但可以诱导显著的肝毒性.
- 5-FU的肝毒性与亡,氧化应激和炎症有关.
- 诺比素是类水果中的一种黄类物质,具有抗癌和抗炎性质.
研究的目的:
- 在雄性大鼠中研究nobiletin对5-fluorouracil诱导的肝毒性的保护作用.
- 评估nobiletin对肝脏炎症,亡和氧化应激标志物的影响.
- 为了评估特定酶表达的变化和组织病理学变化的变化.
主要方法:
- 28只雄性白化老鼠被分为四组:对照组 (玉米油),仅诺比丁,仅5-FU,以及诺比丁+5-FU.
- 诺比素 (10 mg/kg) 被口服14天;5-FU (150 mg/kg) 作为单次腹膜内注射在第14天.
- 血清和肝脏组织被分析为肝功能测试,炎症标记 (IL-6,IL-10),亡标记 (caspase-3),氧化应激标记 (MDA,GSH) 和酶表达 (HO-1,NQO1).
- 进行了肝脏组织的组织病理学检查.
主要成果:
- 诺比丁的使用显著降低了5-FU诱导的肝毒性.
- 关键发现包括降低了酶-3水平 (亡),降低了甲 (氧化应激),增加了Hemeoxygenase-1和NADPH氨酸脱酶-1的表达.
- 组织病理学分析显示,在接受nobiletin治疗的组中,肝细胞拥堵和炎症透减少.
结论:
- 诺比林在老鼠中显示出明显的保护作用,防止5-甲诱导的肝毒性.
- 保护机制包括抑制亡和氧化应激通路.
- 诺比丁显示出作为治疗剂的潜力,可以减轻化疗引起的肝损伤.
相关概念视频
Hepatic Drug Excretion: Influencing Factors
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Drug Toxicity: Risk factors
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...
Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...


