TY - JOUR
T1 - The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain
AU - Astiz, Mariana
AU - De Alaniz, María J.T.
AU - Marra, Carlos Alberto
N1 - Funding Information:
This study was supported by a Grant [PIP #0697] from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. We would like to thank Vet. J. M. Lofeudo for animal handling, clinical evaluation and collaboration for brain dissections, and Mrs. C. Zardis de Cobeñas, E. Illara de Bozzolo, C. Pallanza de Stringa, and N. Cristalli for their excellent technical assistance.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/12
Y1 - 2012/12
N2 - We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5 weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood-brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100 mg/kg) simultaneously with the pesticide mixture (PM) for 5 weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5 weeks. LA prevented OS and the production of nitrites + nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and α-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E2 and F2α in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.
AB - We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5 weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood-brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100 mg/kg) simultaneously with the pesticide mixture (PM) for 5 weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5 weeks. LA prevented OS and the production of nitrites + nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and α-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E2 and F2α in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.
UR - http://www.scopus.com/inward/record.url?scp=84870063331&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2012.09.003
DO - 10.1016/j.neuint.2012.09.003
M3 - Journal articles
C2 - 22995786
AN - SCOPUS:84870063331
SN - 0197-0186
VL - 61
SP - 1231
EP - 1241
JO - Neurochemistry International
JF - Neurochemistry International
IS - 7
ER -