水飞蓟素可保护实验动物的肝脏免受抗结核药物的毒性影响。
Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals.
机构信息
Department of Pharmacology, Marmara University, Faculty of Pharmacy, Haydarpasa, Istanbul, Turkey.
出版信息
Nutr Metab (Lond). 2008 Jul 5;5:18. doi: 10.1186/1743-7075-5-18.
BACKGROUND
The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs.
METHODS
Male Wistar albino rats weighing 250-300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin.
RESULTS
Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs.
CONCLUSION
The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.
背景
一线抗结核药物异烟肼（INH）、利福平（RIF）和吡嗪酰胺（PZA）仍然是治疗结核病的有效药物，然而，这些药物的使用与组织中的毒性反应有关，特别是在肝脏中，导致肝炎。水飞蓟素是一种从水飞蓟中提取的具有强抗氧化活性的标准植物提取物，已知是一种有效的肝脏保护和肝脏再生剂。本研究旨在探讨水飞蓟素对不同抗结核药物组合引起的肝毒性的保护作用。
方法
雄性 Wistar 白化大鼠体重 250-300 g 形成 6 个研究组，每组 10 只大鼠。动物用异烟肼（50 mg/kg）和利福平（100 mg/kg）腹腔注射；吡嗪酰胺（350 mg/kg）和水飞蓟素（200 mg/kg）灌胃。用 INH+RIF 和 INH+RIF+PZA 联合药物诱导肝毒性。通过与药物共同给予水飞蓟素来研究水飞蓟素的肝保护作用。进行血清生化肝功能测试和肝脏组织病理学检查，以证明水飞蓟素对肝脏的抗结核药物保护作用。
结果
用 INH+RIF 或 INH+RIF+PZA 治疗大鼠可诱导肝毒性，如生化测量所示：血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）活性以及总胆红素水平升高，并且药物治疗动物的白蛋白和总蛋白水平降低。药物治疗动物的肝脏也观察到组织病理学变化。同时给予水飞蓟素可显著降低药物引起的生化和组织学变化。
结论
水飞蓟素的活性成分对动物模型中抗结核药物化疗引起的肝毒性具有保护作用。由于在人体研究中未报告水飞蓟素的显著毒性，因此该植物提取物可作为服用抗结核药物的患者的膳食补充剂。
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