Piotrowski W J, Pietras T, Kurmanowska Z, Nowak D, Marczak J, Marks-Kończalik J, Mazerant P
Department of Pneumology and Allergy, Medical University of Lodz, Poland.
J Appl Toxicol. 1996 Nov-Dec;16(6):501-7. doi: 10.1002/(SICI)1099-1263(199611)16:6<501::AID-JAT379>3.0.CO;2-Z.
Paraquat (Pq) is a herbicide which is very toxic to all animals and to man. It generates free radicals and leads to acute or chronic lung injury and usually to death. So far, the role of lipid peroxidation of cell membranes in the mechanism of its toxicity has not been proved satisfactorily and therefore in the present study we examined the concentration of hydrogen peroxide (H2O2) and various lipid peroxidation products (LPP) such as conjugated dienes (CD), lipid hydroperoxides (LH), malonyldialdehyde (MDA) and Schiff bases in selected organs of the rat given a single intraperitoneal dose 35 mg kg-1 Pq. We also evaluated the influence of a mucolytic and probably antioxidant drug, ambroxol, on Pq-induced changes in the concentration of H2O2 and LPP. Paraquat increased the hepatic concentration of H2O2, CD, LH and MDA by approximately fourfold. Though the dose of Pq was nearly twice the LD50 dose, we did not notice any changes in the concentration of these substances in the critical organ, lung or heart and kidney. Ambroxol alleviated the increase of H2O2 in the liver but did not reduce the concentration of LPP. Moreover, the drug administered alone induced lipid peroxidation in the liver. Our results indicate that Pq dose not induce H2O2 production and lipid peroxidation in the lung but it increases the concentration of H2O2 and LPP in the liver. Ambroxol inhibits the Pq-induced increase in the concentration of H2O2 in the liver without protecting it against lipid peroxidation. Moreover, the drug alone may act as a pro-oxidant.
百草枯（Pq）是一种对所有动物和人类都具有剧毒的除草剂。它会产生自由基，导致急性或慢性肺损伤，通常会导致死亡。到目前为止，细胞膜脂质过氧化在其毒性机制中的作用尚未得到令人满意的证实，因此在本研究中，我们检测了给大鼠腹腔注射一次35 mg/kg Pq后，其选定器官中过氧化氢（H2O2）的浓度以及各种脂质过氧化产物（LPP），如共轭二烯（CD）、脂质氢过氧化物（LH）、丙二醛（MDA）和席夫碱的浓度。我们还评估了一种黏液溶解剂且可能具有抗氧化作用的药物氨溴索对Pq诱导的H2O2和LPP浓度变化的影响。百草枯使肝脏中H2O2、CD、LH和MDA的浓度增加了约四倍。尽管Pq的剂量几乎是半数致死剂量的两倍，但我们并未注意到关键器官肺、心脏和肾脏中这些物质的浓度有任何变化。氨溴索减轻了肝脏中H2O2的增加，但并未降低LPP的浓度。此外，单独给药该药物会诱导肝脏中的脂质过氧化。我们的结果表明，Pq不会在肺中诱导H2O2产生和脂质过氧化，但会增加肝脏中H2O2和LPP的浓度。氨溴索可抑制Pq诱导的肝脏中H2O2浓度增加，但不能保护肝脏免受脂质过氧化的影响。此外，该药物单独使用时可能会作为一种促氧化剂。
