ALH Inhibition as a Molecular Initiating Event in the Adverse Outcome Pathway of Benomyl Toxicity in <i>Caenorhabditis elegans</i>: Relevance for Parkinsonism.

ABSTRACT: Dithiocarbamate fungicides, including benomyl (methyl 1-butylcarbamoyl-2-benzimidazolecarbamate), share a common mechanism of toxicity by inhibiting aldehyde dehydrogenases (ALDHs), enzymes essential for detoxifying reactive aldehydes. One such aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), a dopamine metabolite, is implicated in the catecholaldehyde hypothesis of Parkinson's disease. This study examines ALDH inhibition as the molecular initiating event (MIE) within an adverse outcome pathway (AOP) leading to neurotoxicity. Caenorhabditis elegans at the L4 stage were exposed for 24 h to 10 or 100 μM benomyl. While 10 μM had no significant effect on lethality, growth, or reproduction, 100 μM induced adverse effects, albeit with low lethality. Both doses inhibited ALH activity, an

SUBMITTER: Fernandez-Hubeid LE 

PROVIDER: S-EPMC12471186 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature