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

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.

Microcystin Contamination and Toxicity: Implications for Agriculture and Public Health

“…The two are distinguished from each other by the traditional definition of true aquatic plant, meaning it must be submersed in water for most of its life cycle [ 74 ]. Terrestrial plants, in contrast, spend their life cycle on land and root directly into the soil [ 75 ]. Those that can withstand periods of standing water are still classified as terrestrial, land-dwelling plants [ 75 ].…”

“…Terrestrial plants, in contrast, spend their life cycle on land and root directly into the soil [ 75 ]. Those that can withstand periods of standing water are still classified as terrestrial, land-dwelling plants [ 75 ]. Of the two, terrestrial plants have received significant attention where crops are concerned, as those are directly consumed [ 76 ].…”

“…In a survey of 38 crop species ranging from leafy greens to root vegetables, all reported losses of at least 30% in total leaf surface area [ 80 ]. Further analysis suggests that microcystins play a direct role in the inhibition of photosynthetic activities and can cause tissue death, increase oxidative stress, reduce membrane integrity, and impair the ability of roots to absorb nutrients [ 74 , 75 , 77 , 78 , 79 , 80 ]. Anomalies in tissue structure were apparent in crops grown hydroponically, with high concentration of microcystins (≥10 µg/L) [ 77 ].…”

Impacts of Microcystins on Morphological and Physiological Parameters of Agricultural Plants: A Review

“…Histological analysis showed significant alterations in the root tissues affecting the pericycle and endodermis and, for instance, an increase in the number of stomata on the abaxial side of P. vulgaris exposed to (D-Leu1) MC-LR [ 27 ]. Both MC variants induced lipid peroxidation and inhibited total phosphatase activity [ 27 , 28 ].…”

The 6th Iberian and 2nd Ibero-American Cyanotoxin Congress CIC2019

“…[D-Leu1] MC-LR is frequently reported in water bodies throughout America and shows clear toxic potency differences with MC-LR, with greater phosphatase activity inhibition in both animal and plant models. The effects on plants ( Phaseolus vulgaris ) can be observed from germination at fairly low concentrations [ 12 , 13 ]. This may be a warning for not only managers to be aware of most minority compounds that challenge the accuracy of methods, but also for researchers to study the potential toxic effects of Anabaenopeptins and Oscilamide, among others.…”