Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate

Abstract

In this 28 day-study, we evaluated the effects of herbicide glyphosate administered by gavage to Wistar rats at daily doses equivalent to 0.1 of the acceptable operator exposure level (AOEL), 0.5 of the consumer acceptable daily intake (ADI), 1.75 (corresponding to the chronic population-adjusted dose, cPAD), and 10 mg kg-1 body weight (bw) (corresponding to 100 times the AOEL). At the end of each treatment, the body and liver weights were measured and compared with their baseline values. DNA damage in leukocytes and liver tissue was estimated with the alkaline comet assay. Oxidative stress was evaluated using a battery of endpoints to establish lipid peroxidation via thiobarbituric reactive substances (TBARS) level, level of reactive oxygen species (ROS), glutathione (GSH) level, and the activity of glutathione peroxidase (GSH-Px). Total cholinesterase activity and the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also measured. The exposed animals gained less weight than control. Treatment resulted in significantly higher primary DNA damage in the liver cells and leukocytes. Glyphosate exposure significantly lowered TBARS in the liver of the AOEL, ADI, and cPAD groups, and in plasma in the AOEL and cPAD group. 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. 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.

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

“…The decreased activities of CAT and SOD can be used to indicate the accumulation of superoxide radicals and/or hydroxyl radicals in the liver. GSH, as a nonenzymatic scavenger, can scavenge a wide variety of reactive species [38]. GSH-Px works together with CAT to scavenge excess lipid peroxide and hydrogen, which is helpful for eliminating peroxide during the reaction between GSH and H 2 O 2 [27].…”

Lufenuron induces reproductive toxicity and genotoxic effects in pregnant albino rats and their fetuses

“…Oxidant-mediated responses, such as apoptotic or necrotic cell death, membrane lipid peroxidation, metabolic perturbation, and deregulation of several signaling pathways) are several well-known toxicological effects of insecticides 93,94 . Hence, the study of antioxidant enzymes has been used as a popular method to evaluate the response of multiple animal models, including rats, mice, fish, and green snake head, under pesticide-induced stress conditions 78,[95][96][97][98][99][100] . In the present study, lufenuron was found to increase the level of MDA and decrease the level of GPx and SOD enzymes in liver cells in mothers and their fetuses in a dose-dependent manner, which refers to the oxidative stress posed by the insecticide on the liver cells of the treated animals.…”

Effect of in ovo glyphosate injection on embryonic development, serum biochemistry, antioxidant status and histopathological changes in newly hatched chicks

“…Data for liver and kidney weights have been more variable. For example, one report indicated decreases in liver weight (Ren et al, ), another increase in organ weights of liver, brain, kidney and heart (Cox, ; El‐Shenawy, ; Milić et al, ), and another study reported no changes in liver weight (Çağlar & Kolankaya, ). The U.S. Environmental Protection Agency (EPA) suggested that they depended on glyphosate concentration and animal species (EPA, ).…”