engleski

Genetic damage, cholinesterase and unconnected oxidative stress in glyphosate exposed Wistar rats

We investigated the effect of low-dose exposure to glyphosate on 3 months old male Wistar rats that received orally for 28-day doses of 0.1 mg kg-1 b.w. of the acceptable operator exposure level-(AOEL), 0.5 mg kg-1 b.w. consumers acceptable daily intake (ADI), 1.75 mg kg-1 b.w. of the chronic population-adjusted dose (cPAD), 10 mg kg-1 b.w. (100xAOEL) and the same volume of phosphate buffer without glyphosate (negative control). Positive control received 300 mg kg-1 b.w. of ethyl methanesulphonate (EMS) over the last three days of experiment.The samples of whole blood, plasma and liver samples were analyzed for the levels of plasma cholinesterase activity, oxidative stress (lipid peroxidation (thiobarbituric reactive substances, TBARS), glutathione(GSH), glutathione peroxidase (GSH-Px), reactive oxidative species (ROS)) and DNA damage in whole blood and small (non-parenchymal cells) and medium (parenchymal cells-hepatocytes) liver cells.The exposed animals gained less weight than control. The cPAD and the 100xAOEL groups' liver weight increased. AChE was inhibited with all treatments, but the AOEL and ADI groups significantly differed from control. Total ChE and plasma/liver ROS/GSH levels did not significantly differ from control, except for the 35 % decrease in ChE in the AOEL and ADI groups and a significant drop in liver GSH in the cPAD and 100xAOEL groups. AOEL and ADI blood GSH-Px activity dropped significantly, but in the liver it significantly increased in the ADI, cPAD, and 100xAOEL groups vs. control. Exposure lowered TBARS values in all exposed groups, with significant liver changes in the AOEL, ADI, and cPAD groups and plasma changes in the AOEL and cPAD group. Exposure also produced significant primary DNA damage in the leukocytes and liver cells. All these findings show that even exposure to low glyphosate levels can have serious adverse effects and points to a need to change the approach to risk assessment of low-level chronic/sub-chronic glyphosate exposure, where oxidative stress is not necessarily related to the genetic damage and AChE inhibition.This work was financially supported by Project Organic Pollutants in Environment – Markers and Biomarkers of Toxicity (OPENTOX), funded by the Croatian Science Foundation (grant number 8366).

glyphosate ; Wistar rats ; oxidative stress ; comet assay ; micronucleus assay

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