Mohammadi-Karakani Ali, Ghazi-Khansari Mahmoud, Sotoudeh Masoud
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P. O. Box 13145-784, Tehran, and Alborz Hospital, Social Security Organization, Karaj, Iran.
Clin Chim Acta. 2006 May;367(1-2):170-4. doi: 10.1016/j.cca.2005.12.012. Epub 2006 Feb 3.
Paraquat is a controversial and one of the most commonly used herbicides in the world. Although liver, kidney, heart and CNS are affected, lung damage resulting to pulmonary fibrosis is the usual cause of deaths in the cases with intoxication. The mechanism of paraquat toxicity is not clear but probably includes the induction of lipid peroxidation of unsaturated fatty acids. Lisinopril, an angiotensin-converting enzyme inhibitor (ACEI), an antihypertensive drug, has beneficial effects on the treatment of fibrosis. The antifibrotic effect of lisinopril has shown to be due to inhibition of synthesis of angiotensin II that causes stimulation of fibroblast proliferation and collagen synthesis.
Male albino Wistar rats were used in the experiments (weighing 150-300 g). The animals were divided into 5 groups: group I received saline, group II received lisinopril (1 mg/kg; po), group III was given a single i.p. dose of 20 mg/kg paraquat, group IV (treatment group) received lisinopril after single a i.p. dose of 20 mg/kg paraquat, and group V (pre-treatment group) received lisinopril before a single i.p. dose of 20 mg/kg paraquat. After 21 days of treatment, the level of hydroxyproline and the degree of lipid peroxidation were determined in the lung tissue of the animals and the lungs were examined histologically for fibrosis.
Paraquat caused a significant increase in hydroxyproline content and lisinopril significantly decreased the amount hydroxyproline (p<0.001) in the lung tissue of the rats. The histological examination also indicated that lisinopril can effectively protect the paraquat-induced lung fibrosis. The lipid peroxidation levels in the lung were not significantly changed when compared to the control group.
The antifibrotic effect of lisinopril may be due to inhibition of angiotensin II or proline moiety, which is a common structural in all ACEI, drugs.
百草枯是一种存在争议且在全球使用最为广泛的除草剂之一。尽管肝脏、肾脏、心脏和中枢神经系统都会受到影响，但导致肺纤维化的肺部损伤是中毒病例中常见的死亡原因。百草枯毒性的机制尚不清楚，但可能包括诱导不饱和脂肪酸的脂质过氧化。赖诺普利是一种血管紧张素转换酶抑制剂（ACEI），一种降压药物，对纤维化治疗具有有益作用。赖诺普利的抗纤维化作用已表明是由于抑制了导致成纤维细胞增殖和胶原蛋白合成受刺激的血管紧张素II的合成。
实验采用雄性白化Wistar大鼠（体重150 - 300克）。动物被分为5组：第一组接受生理盐水，第二组接受赖诺普利（1毫克/千克；口服），第三组腹腔注射单次剂量20毫克/千克百草枯，第四组（治疗组）在腹腔注射单次剂量20毫克/千克百草枯后接受赖诺普利，第五组（预处理组）在腹腔注射单次剂量20毫克/千克百草枯前接受赖诺普利。治疗21天后，测定动物肺组织中羟脯氨酸水平和脂质过氧化程度，并对肺进行组织学检查以评估纤维化情况。
百草枯导致大鼠肺组织中羟脯氨酸含量显著增加，而赖诺普利显著降低了羟脯氨酸含量（p<0.001）。组织学检查还表明，赖诺普利可有效保护百草枯诱导的肺纤维化。与对照组相比，肺中的脂质过氧化水平没有显著变化。
赖诺普利的抗纤维化作用可能是由于抑制了血管紧张素II或脯氨酸部分，脯氨酸部分是所有ACEI类药物的共同结构。
