Pal Ravinder, Rana Satyavati, Vaiphei Kim, Singh Kartar
Department of Gastroenterology & Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Trop Gastroenterol. 2008 Jul-Sep;29(3):153-9.
Isoniazid (INH) and Rifampicin (RIF) are hepatotoxic drugs. Oxidative stress has been reported as one of the mechanisms of INH+RIF induced hepatotoxicity.
Intragastric administration of INH and RIF (50 mg/kg body weight/day each) for 28 days in Wistar rats is hepatotoxic, indicated by raised transaminases and histology. Carotenoids have antioxidant properties. Therefore, different doses of carotenoids (2.5, 5, 10 and 20 mg/kg body weight/day) were administered to study the hepatoprotective effect against INH+RIF.
The higher doses of carotenoids i.e.10 and 20 mg/kg body weight/day showed partial hepatoprotection indicated by return to normal of liver transaminase level and of liver histology in 33.3% of rats. There was no further protective effect seen by increasing the dose of carotenoids from 10 to 20 mg/kg body weight/day. Lower doses of carotenoids, i.e., 2.5 and 5 mg/kg body weight/day were not effective.
Thus, a minimum dose with maximum hepatoprotection (10 mg/kg b.wt/ day) was selected as the optimum dose in the present study. The hepatoprotective nature of carotenoids in INH+RIF treated rats may be attributed to their antioxidative property.
异烟肼(INH)和利福平(RIF)是具有肝毒性的药物。氧化应激被报道为INH + RIF诱导肝毒性的机制之一。
在Wistar大鼠中,以50毫克/千克体重/天的剂量分别灌胃给予INH和RIF,持续28天,这会导致肝毒性,表现为转氨酶升高和组织学变化。类胡萝卜素具有抗氧化特性。因此,给予不同剂量的类胡萝卜素(2.5、5、10和20毫克/千克体重/天),以研究其对INH + RIF的肝保护作用。
较高剂量的类胡萝卜素,即10和20毫克/千克体重/天,显示出部分肝保护作用,表现为33.3%的大鼠肝脏转氨酶水平和肝脏组织学恢复正常。将类胡萝卜素剂量从10毫克/千克体重/天增加到20毫克/千克体重/天,未见进一步的保护作用。较低剂量的类胡萝卜素,即2.5和5毫克/千克体重/天,无效。
因此,在本研究中选择了具有最大肝保护作用的最小剂量(10毫克/千克体重/天)作为最佳剂量。类胡萝卜素在INH + RIF处理的大鼠中的肝保护作用可能归因于其抗氧化特性。