Acute neurotoxic effects of mancozeb and maneb in mesencephalic neuronal cultures are associated with mitochondrial dysfunction.
Level 5 - mechanism / opinion, no new human data
In vitro bench study using isolated rat cells and mitochondria.
PubMed 16889834 · doi:10.1016/j.neuro.2006.07.009
What was done
Primary mesencephalic cell cultures derived from embryonic day 15 Sprague-Dawley rats were treated in vitro with the fungicides mancozeb (MZ) or maneb (MB) at concentrations ranging from 10 to 120 µM for 24 hours. The study also tested their primary metabolite, ethylene thiourea, and assessed the individual contributions of the organic and manganese metal components. Toxicity was measured via dopamine and GABA high-affinity transporter activity, tyrosine hydroxylase-positive cell counts, and general cell viability. In addition, isolated adult rat brain mitochondria were used to measure ATP levels, NADH-linked state 3 respiration, and mitochondrial uncoupling.
What was found
Exposure to 10–120 µM MZ or MB caused a dose-dependent reduction in cell viability, tyrosine hydroxylase-positive neurons, and both dopamine (DA) and GABA transporter activity. MZ and MB displayed similar toxic potencies, with no difference in sensitivity observed between DA and GABA mesencephalic neuronal populations. Ethylene thiourea was not cytotoxic. At non-cytotoxic exposure levels, both fungicides decreased cellular ATP in a dose-dependent manner. In isolated brain mitochondria, both compounds inhibited NADH-linked state 3 respiration and induced mild-to-moderate mitochondrial uncoupling. Exact percentages, IC50 values, and confidence intervals were not reported in the abstract.
Why it matters
The findings indicate that the fungicide mancozeb shares the neurotoxic potency of maneb, showing that its toxicity extends beyond dopaminergic neurons to GABAergic neurons through parent-compound disruption of mitochondrial energy metabolism.
Limits
The study is restricted to short-term (24-hour) acute in vitro exposures in embryonic rat neurons and isolated adult mitochondria, which may not reflect chronic, low-dose human environmental exposures. Precise numerical effect sizes, variance measures, and replicate numbers were omitted from the abstract.
Cited by
- supports Maneb and mancozeb are fungicides that act as mitochondrial toxins.