Abstract
The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater wax moth, Galleria mellonella, with physiologically relevant doses of okadaic acid by direct injection into the haemocoel (body cavity) and/or gavage (force-feeding). We monitored larval survival and employed a range of cellular and biochemical assays to assess the potential harmful effects of okadaic acid. Okadaic acid at concentrations ≥ 75 ng/larva (≥ 242 μg/kg) led to significant reductions in larval survival (> 65%) and circulating haemocyte (blood cell) numbers (> 50%) within 24 h post-inoculation. In the haemolymph, okadaic acid reduced haemocyte viability and increased phenoloxidase activities. In the midgut, okadaic acid induced oxidative damage as determined by increases in superoxide dismutase activity and levels of malondialdehyde (i.e. lipid peroxidation). Our observations of insect larvae correspond broadly to data published using rodent models of shellfish-poisoning toxidrome, including complementary LD50 values: 206–242 μg/kg in mice, ~ 239 μg/kg in G. mellonella. These data support the use of this insect as a surrogate model for the investigation of marine toxins, which offers distinct ethical and financial incentives.
Highlights
Diarrhetic shellfish poisoning (DSP) is one of several recognised shellfish-poisoning syndromes including amnesic, neurotoxic, and paralytic
This falls within the range of LD50 values calculated for Okadaic acid (OA) administered via intraperitoneal injection in the mouse bioassay (Table 1)
We present clear evidence that G. mellonella larvae exposed to OA have comparable LD50 values to rodent models (Fig. 1, Table 1) and display broad symptoms of immune-cytotoxicity (Figs. 2 and 3) and oxidative damage (Fig. 6)
Summary
Diarrhetic shellfish poisoning (DSP) is one of several recognised shellfish-poisoning syndromes including amnesic, neurotoxic, and paralytic. Crustaceans, sea urchins, and finfish contaminated with the polyether toxin, okadaic acid (C44H68O13), DSP manifests as nausea, vomiting, diarrhoea, abdominal cramps, and chills (Vale and Sampayo 2002; Valdiglesias et al 2013). These symptoms tend to develop within 4 h of intoxication and can last for several days. The occurrences of harmful algal blooms and the incidences of human intoxication from contaminated shellfish are predicted to increase annually due to climate change (Gobler et al 2017) This represents a significant health concern for the public and additional financial burden for the aquaculture and fishing industries (Gobler et al 2017)
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