[D-Leu1]MC-LR Has Lower PP1 Inhibitory Capability and Greater Toxic Potency than MC-LR in Animal and Plant Tissues

SEDAN, DANIELA; MALAISSI, LUCIANO; VACCARINI, CRISTIAN ADRIÁN; VENTOSI, EZEQUIEL; LAGUENS, MARTÍN; ROSSO, LORENA; GIANNUZZI, LEDA; ANDRINOLO, DARÍO

Toxins

MDPI

Lugar: Basel; Año: 2020 vol. 12 p. 632 - 649

Two microcystins, MC-LR and [D-Leu1]MC-LR, present in La Plata Basin blooms, aredifferentiated by substitution of D-Alanine for D-Leucine at position 1. Our objective was to evaluateacute 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 ug/kg), with an increased liver/body weight ratio and intrahepatic hemorrhages in mice exposedto 50?200 ug [D-Leu1]MC-LR/kg and slight steatosis after a single 25 ug [D-Leu1]MC-LR/kg i.p.dose. Our study in the plant model showed alterations in germination, development, morphologyand TBARs levels after a single contact with the toxins during imbibition (3.5 and 15 ug/mL), thosetreated with [D-Leu1]MC-LR being more affected than those treated with the same concentrationof MC-LR. Protein phosphatase 1 (PP1) IC50 values were 40.6 nM and 5.3 nM for [D-Leu1]MC-LRand MC-LR, respectively. However, the total phosphatase activity test in root homogenate showed60% inhibition for [D-Leu1]MC-LR and 12% for MC-LR. In mouse liver homogenate, 50% inhibitionwas observed for [D-Leu1]MC-LR and 40% for MC-LR. Our findings indicate the need for furtherresearch into [D-Leu1]MC-LR toxicity since together with oxidative stress, the possible inhibition ofother phosphatases could explain the dierences detected in the potency of the two toxins.