Terbuthylazine toxicity through a 28-day study: oxidative stress responses and primary DNA damage in the blood of adult male Wistar rats

Autor: Mikolić, Anja, Žunec, Suzana, Kašuba, Vilena, Micek, Vedran, Milić, Mirta, Pizent, Alica, Tariba Lovaković, Blanka, Lucić Vrdoljak, Ana, Kopjar, Nevenka, Želježić, Davor
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Popis: Terbuthylazine is a chloro-triazine herbicide that acts primarily as an inhibitor of photosynthesis. It is used mainly in the production of maize but is also applied in the cultivation of various fruits, and vegetables, as well as in forestry. We evaluated the in vivo effects of terbuthylazine following a 28- day oral administration in adult male Wistar rats at 2.300 mg/kg b.w./day, 0.400 mg/kg b.w./day, and 0.004 mg/kg b.w./day. After treatment, oxidative stress responses were measured in the blood of both the terbuthylazine-treated and the control rats using biomarkers of lipid peroxidation, activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. To establish DNA damaging effects, we applied an alkaline comet assay on the leukocytes of the exposed and control animals. Exposure to terbuthylazine slightly disturbed lipid peroxidation, which was not dose-dependent. Treatment also led to increases of GSH-Px activity in blood, which was statistically significant at 0.400 mg/kg b.w./day. The observed increase of SOD activity in erythrocytes was most prominent at the highest dose tested. On the other hand, plasma SOD activity dropped significantly at two lower doses. Catalase activity in plasma decreased, which was statistically significant at the highest dose. Terbuthylazine produced measurable effects on leukocyte rat DNA. Based on the values measured for comet tail length and tail intensity, which were both lower at the two higher concentrations, it can be concluded that one of possible mechanisms of terbuthylazine’s effect on the DNA molecule includes intercalation. This may in turn slow down the migration of DNA during electrophoresis. Taken together, our findings suggest that the 28-day exposure of rats to very low doses of terbuthylazine, which were within toxicology reference values, resulted in oxidative stress responses and low-level DNA instability. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. This work was financially supported by Project No. 8366 Organic Pollutants in Environment - Markers and Biomarkers of Toxicity (OPENTOX), funded by the Croatian Science Foundation.
Databáze: OpenAIRE