Original scientific paper
https://doi.org/10.2478/aiht-2018-69-3114
Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate
Mirta Milić
orcid.org/0000-0002-9837-7185
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Suzana Žunec
orcid.org/0000-0002-7710-8250
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Vedran Micek
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Vilena Kašuba
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Anja Mikolić
orcid.org/0000-0002-9031-0410
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Blanka Tariba Lovaković
orcid.org/0000-0001-5908-506X
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Tanja Živković Semren
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Ivan Pavičić
orcid.org/0000-0003-2697-6514
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Ana Marija Marjanović Čermak
orcid.org/0000-0002-9477-1329
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Alica Pizent
orcid.org/0000-0003-0216-0166
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Ana Lucić Vrdoljak
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
Rafael Valencia-Quintana
; Laboratorio “Rafael Villalobos-Pietrini” de Toxicología Genómica y Química Ambiental, Facultad de Agrobiología, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico
Juana Sánchez-Alarcón
; Laboratorio “Rafael Villalobos-Pietrini” de Toxicología Genómica y Química Ambiental, Facultad de Agrobiología, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico
Davor Želježić
; Institute for Medical Research and Occupational Health, Zagreb, Croatia
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.
Keywords
ADI; alkaline comet assay; AOEL; cholinesterase activity; cPAD; glutathione; glutathione peroxidase; lipid peroxidation; organophosphate pesticide; ROS
Hrčak ID:
202268
URI
Publication date:
27.6.2018.
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