Oxidative imbalance induced by dithiocarbamate fungicide, Mancozeb aborts Nrf2 anti-oxidant signaling pathway protection in Vero cell line

Indiscriminate use of the dithiocarbamate fungicide mancozeb (MZB) presents serious risks to both human health and environment. These risks are exacerbated during xenobiotic detoxification in kidneys, where glomerular filtration and excretion can lead to the accumulatation of degradation products in renal cells, rendering them more susceptible to toxic effects. Present study examined cytotoxicity of MZB (1–14 μM) in Vero cells, a sensitive model for nephrotoxicity assessment, over different time periods (6–48 h) and detected EC₅₀ of 11 μM. MZB cytotoxicity was dose- and time-dependent, as shown by a 29 ± 0.02 % cell viability at 14 μM and an EC₅₀ of 9 ± 1 μM at 48 hours. DNA damage at 11 μM MZB (EC₅₀) was evidenced as increased tail length (89 ± 9 μm), tail moment (62 ± 10 a.u.), and tail DNA content (60 ± 6 %). Cytotoxic effects of MZB were associated with the generation of reactive oxygen species (13 ± 0.1 RFU), upregulation of the pro-apoptotic Bax gene, activation of Caspase-3, and downregulation of the anti-apoptotic Bcl-2 gene. The study identified MZB induced redox imbalance and oxidative stress in Vero cells through the disruption of Nrf2-mediated antioxidant signaling pathways.