Effects of Rotenone and other Mitochondrial Complex I Inhibitors on the Brine Shrimp Artemia

Brine shrimp (Artemia) nauplii was used to asses the toxicity of rotenone, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), MPP+ (1-methyl-4-phenylpyridinium) and the effect of L-DOPA co-treatment with rotenone. Rotenone had a dose dependent effect on mortality (LC50: 0.37±0.04 μM mean±SE, n = 24), while MPTP and MPP+ proved to be toxic in millimolar range (LC50: 0.21 ±0.09 mM and 0.20±0.08 mM, respectively, n=4). L-DOPA (50-200 μM) co-treatment increased the survival of the rotenone-treated animals (LC50: 0.5±0.23 μM, 1.03±0.66 μM, and 0.76±0.52 μM, respectively). In the whole body tissue homogenates of Artemia, sublethal (up to 0.3 uM) concentrations of rotenone increased the glutathione S-transferase (GST) activity by up to 50 about percent (LC50: 53.3 ±6.8 nM/min/mg protein, against 34.7±3.6 nM/min/mg protein, n=4). Nauplii treated in 100 mM L-DOPA and rotenone together showed further increase of GST activity all across the range of rotenone concentrations. These results on Artemia nauplii show similarities with other animal models, when complex I inhibitors were tested. Biochemical measurements suggest a protective role of L-DOPA by increasing the GST activity as part of the intracellular defences during toxin-evoked oxidative stress.