This study evaluated the sensitivity of the apple snail Pomacea canaliculata to the insecticides cypermethrin (CYP), a type II pyrethroid, and spirotetramat (STM), a new-generation tetramic acid. Initially, the LC50 values were determined for adult male and female snails, revealing a high tolerance to both compounds, with values of 65.6 mg/L for CYP and 12.8 mg/L for STM. Subsequently, female snails were exposed to sublethal concentrations of both pesticides individually and in combination for ten days. Several biomarkers, including biochemical parameters and histopathological changes, were studied in the digestive gland. The two-factor ANOVA analysis showed that of all the biochemical parameters evaluated, only total protein, uric acid, glutathione S-transferase, and lactate dehydrogenase activity were affected by individual CYP treatment (0.1 mg/L) compared to the control. Additionally, lactate dehydrogenase activity was affected by individual and combined STM treatments, showing a hormesis pattern. Triacylglycerol content showed no differences between the control and the different treatments. However, the 0.1 mg/L CYP +0.1 mg/L STM treatment resulted in the highest triacylglycerol accumulation. Semi-quantitative analysis of the histopathological index (HI) revealed that the exposure of both CYP and STM led to a significantly higher HI than in controls. However, no dose-dependent pattern was observed, suggesting a high sensitivity of the digestive gland. The integrated biomarker index (IBRv2) analysis showed that CYP caused greater damage than STM. The combined treatment exhibited an antagonistic interaction between CYP and STM. In conclusion, this study demonstrates the high tolerance of P. canaliculata to pesticides from different chemical groups. This remarkable adaptability may explain its success in adverse environmental conditions, establishing it as one of the world's most damaging invasive species. The study also reinforces the value of histopathological changes as the most appropriate and sensitive biomarker for assessing pesticide contamination in this organism.
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