Oxidative stress biomarkers in workers exposed to mancozeb

Mancozeb (MCZ) is a dithiocarbamate, widely used in agriculture as a fungicide. MCZ could determine immunotoxic and hepatotoxic effects through the increase of reactive oxygen species (ROS), which can induce peroxidation of biological molecules in the liver, blood and bone marrow. Peroxidation of carbohydrates, proteins and lipids determines the formation of new molecules that can be used as oxidative stress biomarkers: respectively, advanced glycation endproducts (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA). Aim of the study is to determine the level of oxidative stress in a population of workers professionally exposed to MCZ, measuring the hematic concentration of ROS and using AGE, AOPP and MDA as biomarkers of effect. A cohort of 40 male subjects has been recruited. Quantitative exposure was assessed by measuring the metabolite ethylenthiourea (ETU) in LC/MS in a sample of urines collected at the end of the work shift. Circulating levels of ROS, AGE, AOPP and MDA were determined on serum samples through spectrophotometry and fluorometry, using a multifunctional micro plate reader. Levels of ETU (p < 0.5), ROS (p < 0.01), AOPP (p < 0.01) and MDA (p < 0.05) resulted significantly increased in exposed subjects vs the control group. On the other hand, MCZ exposure does not seem to alter the concentration of AGE in the serum. AOPP and ROS emerged as early markers of oxidative stress that can be considered adequately sensitive in subjects exposed to MCZ. Even if not very specific, these biomarkers confirm the hypothesis that oxidative stress may be the main mechanism of toxicity of MCZ.