Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats. (5th January 2018)

• Record Type: Journal Article
• Authors: Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor
• Is Part Of: Chemico-biological interactions. Volume 279(2018)
• Page Start: 51
• Page End: 63
• Publication Date: 2018-01-05
• Subjects: Acetylcholinesterase -- Genotoxicity -- HPLC-UV DAD analysis -- Organophosphate pesticide -- Oxidative stress; AChE acethylcholinesterase -- BChE butyrylcholinesterase -- ROS reactive oxygen species -- GSH glutathione -- GSH-Px glutathione peroxidase -- SOD superoxide dismutase -- HPLC-UV DAD high performance liquid chromatography with UV diode array detector -- ADI acceptable daily intake -- AOEL acceptable operator exposure -- ARfD acute reference dose -- MRL maximum residue level -- TBARS thiobarbituric reactive substance -- TAC total antioxidant capacity -- TPTZ 2, 4, 6-tri[2-pyridyl]-s-triatine -- DCF-DA 2′, 7′-dichlorofluorescin diacetate -- MBCI monochlorobimane; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2017.10.029
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3, 5, 6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Graphical abstract: Highlights: Chlorpyrifos toxicity on in vivo rat model following 28-days exposure was studied. Parent compound and its primary metabolite were detected in plasma and brain cells. Biochemical and enzyme activity-based endpoints were slightly changed by treatment. Chlorpyrifos had the potency to inflict DNA damage in both biological matrices. Brain cells had lower level of primary DNA damage than leukocytes.