Effects of neonatal quinalphos exposure and subsequent withdrawal on free radical generation and antioxidative...

Ten-day-old rat pups were given quinalphos (QP, 0.5 mg kg(-1)) orally up to postnatal days (PND) 21 or 45. A group of rats exposed to QP was withdrawn from the treatment at PND 21 and was killed at PND 45 for the withdrawal study. Acetylcholinesterase decreased in the brain and blood after QP exposure but recovered after withdrawal. Superoxide radical generation in brain was increased by 43%, 59% and 39% following exposure up to PND 21 and 45 and in the withdrawal group, respectively. Quinalphos did not alter hydrogen peroxide formation but increased hydroxyl radical (19%) production at PND 45. Quinalphos elevated the activities of superoxide dismutase by 30%, (although the increase from 0.24 to 0.31 was physiologically not significant) and catalase by 50% at PND 21, which up on withdrawal of the exposure at PND 22 recovered partially or completely at PND 45. However, the continuous exposure up to PND 45 decreased superoxide dismutase (63%) and catalase (31%) activities. Selenium-independent glutathione peroxidase (GPx) was increased at PND 21 (31%) and PND 45 (152%) after QP exposure and there was complete recovery after withdrawal. Selenium-dependent GPx, which was elevated slightly at PND 21, was also normalized after withdrawal. Prolonged exposure to QP did not alter the ascorbic acid content and produced a marked decrease in cerruloplasmin (46%) levels. Brain glutathione levels increased marginally in QP-exposed rats and became normal in the withdrawal group. Quinalphos exposure up to PND 45 enhanced brain lipid peroxidation (28%) and decreased vitamin E levels (15%). It appears that neonatal QP exposure produces cerebral oxidative stress, which may result in deleterious effects on central nervous system function immediately and in later life.