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[D-Leu1]MC-LR Has Lower PP1 Inhibitory Capability and Greater Toxic Potency than MC-LR in Animal and Plant Tissues
Daniela Sedan1,2, Luciano Malaissi1,2, Cristian Adrián Vaccarini1,2
1Center for Environmental Research (CIM), National Council for Scientific and Technical Research (CONICET), National University of La Plata (UNLP), La Plata 1900, Argentina.
Abstract:
Two microcystins, MC-LR and [D-Leu1]MC-LR, present in La Plata Basin blooms, are differentiated by substitution of D-Alanine for D-Leucine at position 1. Our objective was to evaluate acute toxicity of [D-Leu1]MC-LR and MC-LR in mice (N:NIH Swiss) and beans (Phaseolus vulgaris). We observed variations in [D-Leu1]MC-LR lethal doses with respect to those reported for MC-LR (100 μg/kg), with an increased liver/body weight ratio and intrahepatic hemorrhages in mice exposed to 50-200 μg [D-Leu1]MC-LR/kg and slight steatosis after a single 25 μg [D-Leu1]MC-LR/kg i.p. dose. Our study in the plant model showed alterations in germination, development, morphology and TBARs levels after a single contact with the toxins during imbibition (3.5 and 15 µg/mL), those treated with [D-Leu1]MC-LR being more affected than those treated with the same concentration of MC-LR. Protein phosphatase 1 (PP1) IC50 values were 40.6 nM and 5.3 nM for [D-Leu1]MC-LR and MC-LR, respectively. However, the total phosphatase activity test in root homogenate showed 60% inhibition for [D-Leu1]MC-LR and 12% for MC-LR. In mouse liver homogenate, 50% inhibition was observed for [D-Leu1]MC-LR and 40% for MC-LR. Our findings indicate the need for further research into [D-Leu1]MC-LR toxicity since together with oxidative stress, the possible inhibition of other phosphatases could explain the differences detected in the potency of the two toxins.
Insights
[D-Leu1]MC-LR, a microcystin variant, shows distinct toxicity compared to MC-LR in mice and beans. This cyanotoxin variant causes greater effects in plants and alters liver function and weight in mice, indicating unique toxicological properties.
Area of Science:
- Environmental Toxicology
- Biochemistry
- Plant Science
Background:
- Microcystins (MCs) are potent cyanotoxins impacting aquatic ecosystems.
- MC-LR and [D-Leu1]MC-LR are variants found in La Plata Basin blooms.
- Understanding differential toxicity is crucial for risk assessment.
Purpose of the Study:
- To evaluate and compare the acute toxicity of [D-Leu1]MC-LR and MC-LR.
- To assess the effects of these toxins on animal and plant models.
- To investigate the underlying biochemical mechanisms of toxicity.
Main Methods:
- Acute toxicity testing in mice (N:NIH Swiss) and bean plants (Phaseolus vulgaris).
- Histopathological examination of mouse livers and assessment of liver/body weight ratios.
- Evaluation of plant germination, development, morphology, and TBARs levels.
- In vitro assays measuring protein phosphatase 1 (PP1) inhibition and total phosphatase activity in root and liver homogenates.
Main Results:
- [D-Leu1]MC-LR exhibited variations in lethal doses compared to MC-LR.
- Mice exposed to [D-Leu1]MC-LR showed increased liver/body weight ratio and intrahepatic hemorrhages.
- Bean plants treated with [D-Leu1]MC-LR displayed more severe alterations in germination, development, and morphology.
- [D-Leu1]MC-LR demonstrated differential inhibition of phosphatases compared to MC-LR.
Conclusions:
- [D-Leu1]MC-LR possesses unique toxicological properties distinct from MC-LR.
- The higher toxicity in plants and altered effects in mice suggest specific mechanisms of action.
- Further research is needed to elucidate the role of oxidative stress and other phosphatase inhibitions in [D-Leu1]MC-LR toxicity.
