Acute Maneb Exposure Significantly Alters Both Glycolysis and Mitochondrial Function in Neuroblastoma Cells.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory bench study (mechanism-based reasoning with no human clinical data)
PubMed 29767788 · doi:10.1093/toxsci/kfy116
What was done
Researchers exposed human neuroblastoma cells acutely to subtoxic concentrations of the pesticide maneb (down to 6 μM). Using the Seahorse extracellular flux platform, they assessed ATP-linked mitochondrial respiration, nonmitochondrial respiration, proton leak, mitochondrial fuel flexibility across three substrates (pyruvate capacity and glutamine dependency), and glycolytic acidification via lactic acid export. Intracellular ATP and NAD levels were also measured.
What was found
The abstract reports directional effects without providing specific numerical quantities or statistical intervals. Maneb exposure resulted in: - Decreased baseline and maximal mitochondrial oxygen consumption, ATP synthesis, and coupling efficiency. - Increased nonmitochondrial respiration and proton leak. - Loss of fuel flexibility across all three major substrates, with lower pyruvate capacity and glutamine dependency. - Decreased glycolytic acidification from lactic acid export at doses as low as 6 μM. - A drastic decrease in cellular ATP and NAD levels.
Why it matters
The study indicates that maneb acts as a dual metabolic disrupter by inhibiting both aerobic and anaerobic energy production pathways simultaneously, clarifying a potential mechanism for pesticide-linked Parkinson's disease neurotoxicity.
Limits
The investigation was conducted exclusively in immortalized cell culture (in vitro human neuroblastoma cells) and cannot capture complex whole-organism pharmacokinetics, blood-brain barrier dynamics, or neuronal interactions. The abstract does not provide exact numerical effect sizes, sample sizes/replicate counts, exposure durations, or p-values.
Cited by
- supports The dithiocarbamate pesticides maneb and mancozeb are used in laboratory research to model Parkinson's disease by damaging cellular and mitochondrial function.