山莨菪碱对异烟肼和利福平肝毒性的保护作用

异烟肼和利福平联合用药效果良好,二者为目前结核病短程疗法所必需。但异烟肼和利福平合用肝毒性明显增加。山莨菪碱有保肝作用且有其与抗结核药物联用可降低肝损害的临床报道［１］。本实验就山莨菪碱对异烟肼和利福平肝毒性的保护作用及其机制予以探讨。１　材料和方法１１　动物与用药　昆明种小鼠５０只,♀各半,购自河南医科大学实验动物中心,体重（２１３±１８）ｇ,随机分为５组：Ⅰ组（生理盐水对照组）：生理盐水ｉｐ,００１ｍｌ·ｇ－１,每天１次连用５ｄ;Ⅱ组（肝损伤组）：异烟肼＋利福平,异烟肼（广州明兴制…     

利福平与异烟肼联用引起阻塞性黄疸,中毒性肝炎5例报告

利福平与异烟肼联用引起阻塞性黄疸、中毒性肝炎５例报告陈兰英，唐贵珍利福平（ＲＦＰ）与异烟肼（ＩＮＨ）是治疗结核病的主要药物。临床上常以该两药伍用，疗效确切。但两药长期或大剂量应用，可增加肝脏毒性。联用时，利福平的酶促作用，可加快ＩＮＨ转化为肝毒性强的...     

白头翁对利福平和异烟肼肝毒性的影响

目的观察白头翁对利福平、异烟肼致肝毒性的保护作用。方法分别测定肝损害组和白头翁组小鼠的肝SGPT ,肝指数 ,肝匀浆丙二醛以及肝细胞镜检 ,并与对照组比较。结果白头翁组具有对抗利福平、异烟肼引起的SGPT增高和肝自由基的产生 ,减轻两者对肝细胞的损害。肝损害组与对照组和白头翁组比较均有显著性差异(P<0.01)。结论白头翁对利福平、异烟肼致肝损害具有保护作用     

白头翁对利福平和异烟肼肝毒性的影响

目的：观察白头翁对利福平、异烟肼致肝毒性的保护作用。方法：分别测定肝损害组和白头翁组小鼠的肝SGPT，肝指数，肝匀浆丙二醛以及肝细胞镜检，并与对照组比较。结果：白头翁组具有对抗利福平、异烟肼引起的SGPT增高和肝自由基的产生，减轻两对肝细胞的损害。肝损害组与对照组和白头翁组比较均有显性差异（P＜0．01）。结论：白头翁对利福平、异烟肼致肝损害具有保护作用。     

异烟肼与利福平合用致肝毒性增加机制的研究概况

目的:综述抗结核药异烟肼与利福平合用时肝毒性增加机制的研究概况。方法:查询近年来国内外相关报道,综述和分析异烟肼代谢的机制,以及两药合用肝毒性与快慢乙酰化、肝药酶及其他因素的关系。结果:临床研究及动物实验表明异烟肼与利福平二者合用时肝毒性增加有多种论述。结论:利福平可诱导肝药酶加速异烟肼代谢产生肝毒性物质     

异烟肼与利福平合用致肝毒性增加机制的研究概况

目的；综合抗结核药异烟肼与利福平合用时肝毒性增加机制的研究概况。方法：查询近年来国内外相关报道，综述和分析异烟肼代谢的机制，以及两药合用肝毒性与快慢乙酰化，肝药酶其他因素的关系。结果：临床研究及动物实验表明异烟肼与利福平二者合用时肝毒性增加有多种论述。结论：利福平可诱导肝药酶加速异烟肼代谢产生肝毒性物质。     

银杏叶醇提取物对异烟肼和利福平肝毒性保护作用的实验研究

目的 :观察银杏叶醇提取物对异烟肼和利福平肝毒性的保护作用及其机制探讨。方法 :分别测定肝损害组和银杏叶醇提取物大、小剂量组小鼠的血清谷丙转胺酶 (SGPT)、肝指数、肝匀浆丙二醛 (MDA)含量、肝微粒体P4 50和线粒体Ca2 ATP酶活性 ,以及肝病理检查 ,并与对照组比较。结果 :银杏叶醇提取物大、小剂量均可对抗异烟肼和利福平引起的MDA、SGPT、肝微粒体P4 50 的增高 (P <0 .0 5) ,以及对抗其引起的形态学改变 ;银杏叶醇提取物大剂量对抗其线粒体Ca2 ATP酶活性的降低。结论 :银杏叶醇提取物可对抗异烟肼和利福平所致肝毒性。     

抗结核药物所致肝损害的临床分析

<正>药物性肝损害是抗结核药物治疗过程中最常见的副反应,可造成抗结核治疗的中断,影响病人康复。抗结核药物联合应用是目前结核病化疗的基本原则,但联用尤其异烟肼、利福平、吡嗪酰胺联用极易引起肝脏损害,发生率约为15%～30%。研究表明,抗结核药物致药物性肝损害机制主要为内源性、肝毒性和特异性反应,主要表现为肝细胞变     

银杏叶醇提取物对异烟肼和利福平肝毒性保护作用的实验研究

目的:观察银杏叶醇提取物对异烟肼和利福平肝毒性的保护作用及其机制探讨。方法:分别测定肝损害组和银杏叶醇提取物大、小剂量组小鼠的血清谷丙转胺酶(SGPT)、肝指数、肝匀浆丙二醛(MDA)含量、肝微粒体P₄₅₀和线粒体Ca²⁺ ATP酶活性,以及肝病理检查,并与对照组比较。结果:银杏叶醇提取物大、小剂量均可对抗异烟肼和利福平引起的MDA、SGPT、肝微粒体P₄₅₀ 的增高(P<0.05) ,以及对抗其引起的形态学改变;银杏叶醇提取物大剂量对抗其线粒体Ca²⁺ ATP酶活性的降低。结论:银杏叶醇提取物可对抗异烟肼和利福平所致肝毒性。     

全国样本医院抗结核病药呈现减少及市场竞争格局

结核病是由结核杆菌引起的慢性传染病，可累及全身各组织器官，如肺、肾、肠，但以肺结核最为常见。抗结核病药能抑制或杀灭结核杆菌，按疗效、毒性及临床试验应用，将种类较多的抗结核病药分为两类：一线药有异烟肼、利福平、乙胺丁醇、链霉素、吡嗪酰胺等，其特点是疗效高、不良反应少、患者较易接受；二线药有环丙沙星、氧氟沙星、对氨基水杨酸、丙硫异烟肼、卡那霉素等，用于一线用药耐药或因患者因素如HIV感染时。     

The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice

Antitubercular drugs have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. In this study, we aimed to investigate the protective effects of ursodeoxycholic acid (UDCA) on liver injury caused by co-administration with isoniazid and rifampicin, two famous antitubercular drugs. Liver injury was induced by co-treatment with isoniazid (75 mg/kg) and rifampicin (150 mg/kg) for one week. Mice were orally administered with UDCA (15, 50 and 150 mg/kg) 30 min before isoniazid and rifampicin. We show that serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly increased in mice treated with isoniazid plus rifampicin. An obvious fatty accumulation, accompanied by mild necrosis and inflammation, was observed in liver of mice treated with rifampicin plus isoniazid. In addition, isoniazid plus rifampicin resulted in hepatic apoptosis, as determined by terminal dUTP nick-end labeling (TUNEL) staining and caspase-3 activation. Additional experiment showed that isoniazid plus rifampicin significantly increased the level of hepatic malondialdehyde (MDA) and caused glutathione (GSH) depletion and 3-nitrotyrosine (3-NT) residues in liver. UDCA pretreatment significantly attenuated isoniazid plus rifampicin induced oxidative stress in liver. Importantly, UDCA pretreatment significantly alleviated isoniazid plus rifampicin induced hepatic apoptosis. Moreover, UDCA-mediated anti-apoptotic effect seemed to be associated with its regulation of Bcl-2 and Bax gene expression in liver. These findings suggest that UDCA might protect against isoniazid and rifampicin induced liver injury through its anti-oxidative and anti-apoptotic effects.     

阿魏酸钠对异烟肼和利福平肝损害小鼠的保护作用

目的：观察阿魏酸钠对异烟肼(INH)和利福平(RFP)肝毒性的保护作用。方法：分别测定血清谷丙转氨酶(ALT)的活性，肝匀浆中谷胱甘肽(GSH)及脂质过氧化物丙二醛(MDA)的含量，肝微粒体中细胞色素P450及其亚型2E1的活性。结果：阿魏酸钠可对抗INH和RFP合用引起的肝指数、血清ALT水平、肝匀浆中的MDA含量，以及细胞色素P450与亚型P450 2E1活性的升高，增加肝匀浆中GSH含量。病理学检查，阿魏酸钠明显减轻肝细胞的变性和坏死。结论：阿魏酸钠时INH和RFP肝毒性的保护作用与保护肝细胞膜、抑制脂质过氧化反应、清除自由基、降低RFP诱导的细胞色素P450酶系统有关。     

竹节参总皂苷对异烟肼和利福平致小鼠肝损伤的保护作用

目的：研究竹节参总皂苷对异烟肼和利福平合用致小鼠肝损伤的保护作用。方法：灌胃异烟肼（75mg／kg）、利福平（100mg／kg）7d以复制小鼠肝损伤模型。40只雄性Bab1c小鼠随机分为正常对照（等容生理盐水）组、模型（等容生理盐水）组、水飞蓟宾（50mg／kg）组与竹节参总皂苷高、低剂量（100、50mg／kg）组,复制模型的同时灌胃给予相应药物,每天1次,连续7d。测定小鼠肝脏指数、血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性、肝匀浆中丙二醛（MDA）含量、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH．Px）活性及mRNA的表达情况,并作小鼠一般情况与肝组织病理学观察。结果：与正常对照组比较,模型组小鼠肝脏指数显著升高,肝组织ALT、AST活性显著增强,sOD、GSH．Px活性显著减弱,MDA含量显著增加,GSH—Px和SOD。mRNA表达显著减弱（尸〈0．01或P〈0．05）。与模型组比较,竹节参总皂苷高、低剂量组小鼠肝脏指数显著降低,肝组织ALT、AST活性显著减弱,SOD：、GSH．Px活性显著增强,MDA含量显著减少,GSH—PX和SOD：mRNA表达显著增强（P〈0．01或P〈0．05）。正常对照组小鼠肝脏外观正常,肝小叶结构清楚,肝细胞索排列整齐,肝细胞轻微水肿,核结构清晰,肝窦正常;模型组小鼠肝脏明显肿大,质脆,边缘钝而厚,表面呈黄褐色颗粒状,肝细胞弥漫性水肿,胞浆疏松化,胞质色淡,肝细胞点状坏死,散在有炎性细胞浸润;竹节参总皂苷高、低剂量组小鼠肝大体与肝组织病理学均明显改善。结论：竹节参总皂苷对异烟肼和利福平合用致小鼠肝损伤具有明显的保护作用,其机制可能与其抗脂质过氧化有关。     

番茄红素对异烟肼和利福平致大鼠肝损伤的保护作用

目的观察番茄红素对异烟肼(INH)和利福平(RFP)合用致大鼠肝损伤的保护作用并探讨其作用机制。方法给予异烟肼和利福平(各75mg.kg-1)用药4wk制备肝损伤动物模型,分别给予低、中、高剂量番茄红素(10、20、30mg.kg-1),4wk后测定大鼠血清中AST和ALT含量、肝脏指数,以及肝组织匀浆中的MDA、GSH的含量和SOD的活性,并作肝组织病理学检测。结果番茄红素能降低肝脏指数(P<0.05)、降低大鼠血清AST和ALT的含量、降低大鼠肝匀浆中的MDA、增加肝匀浆中GSH、升高SOD(P<0.05或P<0.01),减轻肝组织变性、坏死程度,缓解肝组织的病理改变。结论番茄红素对INH和RFP合用所致的大鼠肝损伤具有保护作用,其作用机制可能与番茄红素的抗脂质过氧化作用有关。     

黄芩苷对异烟肼和利福霉素钠肝损伤小鼠的保护作用研究

目的:研究黄芩苷对异烟肼和利福霉素钠致肝脏毒性的保护作用。方法:将60只小鼠随机分为6组,即正常对照组、肝损伤(异烟肼+利福霉素钠)组、联苯双酯组和黄芩苷高、中、低剂量组。后4组进行肝损伤组相同处理后1h给予相应药物,分别给药8d后测定血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的活性,计算肝指数,用光镜观察肝脏组织细胞病理学的改变情况。结果:与肝损伤组比较,黄芩苷组可降低肝指数水平、血清ALT和AST的活性(P<0.05、P<0.01或P<0.001)及明显减轻肝细胞的变性和坏死。结论:黄芩苷能减轻异烟肼和利福霉素钠引起的肝脏毒性。     

Rifampicin-isoniazid and delayed elimination of theophylline: a case report

This paper reports a case of tuberculosis relapse and chronic obstructive lung disease treated with rifampicin and isoniazid. The subsequent introduction of slow-release theophylline therapy revealed a delay in the theophylline elimination kinetics resulting in a toxic plasma level. Interference with hepatic microsomal enzymes is considered to occur.     

Genetic polymorphisms of drug-metabolizing enzymes and the susceptibility to antituberculosis drug-induced liver injury

Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N-acetyltransferase. Other possible enzymes are CYP2E1 and glutathione S-transferase. There is evidence that polymorphisms of the genes that encode these enzymes may influence the activity of the corresponding drug-metabolizing enzymes. Recent studies demonstrated that these genetic polymorphisms may be associated with the susceptibility to antituberculosis drug-induced liver injury. The proposed risk-associated genotypes are NAT2 slow acetylator (without wild-type NAT2*4 allele), CYP2E1 *1A/*1A (homozygous wild type) and homozygous null GSTM1 genotype. Although the available data in the field are still limited and warrants further confirmation in different ethnic populations with larger sample sizes, it still cast some light on the application of these pharmacogenetic or pharmacogenomic approaches to prevent grave antituberculosis drug-induced liver injury in the near future.     

The comparative action of isoniazid, rifampicin and ethambutol on liver function]

It has been established in experiments on white rats that antituberculous drugs (isoniazid, rifampicin, ethambutol) given in toxic doses affect the liver, its membranes and organelles, inhibit bile production and bioenergy. This is supported by activation of aspartate and alanine aminotransferases, (ALT and AST), alkaline phosphatase in blood serum and acid phosphatase in the liver, by a decrease of the activity of Na(+)-, K(+)-ATPase, succinate dehydrogenase and cytochromoxidase in the liver, lowering of the rate of bile secretion, excretion of bile acids, bilirubin and cholesterol with bile. Provided the drugs are administered in combination, the hepatotoxicity rises, particularly in combination of isoniazid with rifampicin, and especially as isoniazid is combined with rifampicin and ethambutol.