Mitochondrial and lysosomal dysfunction induced by the novel metal-insecticide [Mg(hesp)2(phen)] in the zebrafish (Danio rerio) hepatocyte cell line (ZF-L)

Abstract

The development of novel agrochemical compounds to reduce the use of pesticides with high ecological impact is urgently needed. A complex of Mg with two flavonoids hesperidin and phenanthroline [Mg(hesp)₂(phen)], referred to as MgHP, results in high insecticidal activity against urban, agricultural and forest insect pests. In vitro cytotoxicity biomarkers were used to assess the mechanism of action MgHP on fish cells, as this insecticide can reach the aquatic environment and affect its biota. The cytotoxic effects of MgHP were evaluated at different concentrations (0, 0.1, 1, 10, 100 and 1000 ng mL^-1) in a zebrafish hepatocyte cell line (ZF-L). Twenty-four hours of exposure to high concentrations (10 and 1000 ng mL^-1) of MgHP affected cell confluence and morphology. Mitochondrial activity and lysosomal retention ability decreased as the MgHP concentration was increased. Cell membrane injury, apoptosis, and necrosis were not induced. These results suggested that toxicity to ZF-L cells was due loss of organellar activity caused by MgHP, which may also include activation of an alternative cell death mechanism. However, after 96 h of exposure, the toxic effects of MgHP may be mitigated, even at high concentrations, enabling cellular population recovery. These data provide important information on the mechanism of action of MgHP on hepatocyte fish cells and stimulate analyses to elucidate the cellular responses to MgHP.

Keywords: Apoptosis; Aquatic contamination; Cytotoxicity biomarkers; MgHP; Necrosis.