The global expansion of toxic Microcystis blooms,
and production of cyanotoxins including microcystins, are an increasing
risk to freshwater fish. Differentiating intracellular and extracellular
microcystin toxicity pathways (i.e., within and outside of cyanobacterial
cells) in fish is necessary to assess the severity of risks to populations
that encounter harmful algal blooms in pre-to-postsenescent stages.
To address this, adult and juvenile Rainbow Trout (Oncorhynchus mykiss) were, respectively, exposed
for 96 h to intracellular and extracellular microcystins (0, 20, and
100 μg L–1) produced by Microcystis
aeruginosa. Fish were dissected at 24 h intervals
for histopathology, targeted microcystin quantification, and nontargeted
proteomics. Rainbow Trout accumulated intracellular and extracellular
microcystins in all tissues within 24 h, with greater accumulation
in the extracellular state. Proteomics revealed intracellular and
extracellular microcystins caused sublethal toxicity by significantly
dysregulating proteins linked to the cytoskeletal structure, stress
responses, and DNA repair in all tissues. Pyruvate metabolism in livers,
anion binding in kidneys, and myopathy in muscles were also significantly
impacted. Histopathology corroborated these findings with evidence
of necrosis, apoptosis, and hemorrhage at similar severity in both
microcystin treatments. We demonstrate that sublethal concentrations
of intracellular and extracellular microcystins cause adverse effects
in Rainbow Trout after short-term exposure.