Phenoxyherbicides induce production of free radicals in human erythrocytes: Oxidation of dichlorodihydrofluorescine and dihydrorhodamine 123 by 2,4-D-Na and MCPA-Na

Although it is known that phenoxyacetic herbicides significantly affect the oxidative status of human erythrocytes, there is no direct evidence of their ability to induce free radical production. To demonstrate this phenomenon we investigated the effect of two commonly used phenoxyherbicides–sodium salt of 2,4-dichlorophenoxyacetic acid (2,4-D-Na) and sodium salt of 4-chloro-2-methylphenoxyacetic acid (MCPA-Na) on oxidation of dihydrorhodamine 123 and H2DCFDA as well as on carbonyl group content in cellular proteins. Moreover, haemoglobin denaturation was also measured. The rate of fluorescent probe oxidation was significantly higher for 2,4-D-Na, while both compounds exerted similar effects on protein carbonyl group (an increase in their content) and on denaturation of haemoglobin (no changes were observed). These results and the previous data led us to a conclusion that pro-oxidative action of phenoxyherbicides is strongly dependent on the localization of the substituent in the phenol ring. We also proposed a metabolic reaction chain that explains the mechanism of action of 2,4-D-Na in vivo.