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. 2020 Sep 1:7:1207-1215.
doi: 10.1016/j.toxrep.2020.08.024. eCollection 2020.

Toxicological and genotoxic evaluation of anacardic acid loaded-zein nanoparticles in mice

Jennifer Thayanne Cavalcante de Araújo  1 , Laís Aragão Lima  2 , Everton Pantoja Vale  3 , Manuel Martin-Pastor  4 , Ramille Araújo Lima  2 , Paulo Goberlânio de Barros Silva  2 , Francisco Fabio Oliveira de Sousa  1   3
Affiliations

Toxicological and genotoxic evaluation of anacardic acid loaded-zein nanoparticles in mice

Jennifer Thayanne Cavalcante de Araújo et al. Toxicol Rep. .

Abstract

Anacardic acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing anacardic acid (9.375 μg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated anacardic acid at 2.25 and 112.5 μg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs' relative weight reductions. Blank and anacardic acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.

Keywords: Anacardic acid; Genotoxicity; Micronucleus; Nanoparticles; Subacute toxicity; Zein.

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Conflict of interest statement

The authors report no declarations of interest.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
TEM images of the nanoparticle formulations before dilutions. a) ZAad2, Anacardic acid-loaded zein nanoparticles and b) ZB, Blank zein nanoparticles.
Fig. 2
Fig. 2
¹H NMR spectrum of anacardic acids. The proton signal assignment is indicated with letters that corresponds to the molecule structure shown on the right.
Fig. 3
Fig. 3
Target organs weight variation (organ weight/body weight x 100) in mice orally treated for 7-days with ZAad1, ZAad2, ZB nanoparticles and NC. (A) Spleen, (B) Liver, (C) Kidneys, (D) Stomach, (E) Lung and (F) Heart. (results are express as Mean ± SD). **p < 0.01 ZAad2versus NC, ZB and ZAad1, *p < 0.05 ZAad2versus CN, ZB and ZAad1. ZAad1: Anacardic acid loaded zein nanoparticles administered at 2.25 μg/kg. ZAad2: Anacardic acid loaded zein nanoparticles administered at 112.5 μg/kg; ZB: Blank zein nanoparticles. NC: Negative control group, treated with sterile saline solution 0.9 %.
Fig. 4
Fig. 4
Photomicrographs of representative tissue sections (H&E) showing the histopathology: (A) spleen, (B) liver and (C) kidneys among mice groups NC (Negative control group, treated with sterile saline solution 0.9 %), ZB (Blank zein nanoparticles.), ZAad1 (Anacardic acid loaded zein nanoparticles administered at 2.25 μg/kg) and ZAad2 (Anacardic acid loaded zein nanoparticles administered at 112.5 μg/kg) treated for 7- days. Black arrows indicate the presence of megakaryocytes in all groups in the spleen; circle indicates focus of inflammatory cells in the liver; elliptical indicates the presence of tubular and interstitial hemorrhages and yellow arrow indicates the presence of hyaline cylinder.
Fig. 5
Fig. 5
Photomicrographs of representative tissue sections (H&E) showing the histopathology: (A) heart and (B) lung among mice groups NC (Negative control group, treated with sterile saline solution 0.9 %), ZB (Blank zein nanoparticles.), ZAad1 (Anacardic acid loaded zein nanoparticles administered at 2.25 μg/kg) and ZAad2 (Anacardic acid loaded zein nanoparticles administered at 112.5 μg/kg) treated for 7-days. Dotted circle indicates vacuolation in the heart; Full circle indicates the presence of inflammatory cells and arrow indicating bleeding point in the lung.
Fig. 6
Fig. 6
Photomicrographs of representative tissue sections (H&E) showing the histopathology of the stomach: (A) cardia and (B) fund among mice NC (Negative control group, treated with sterile saline solution 0.9 %), ZB (Blank zein nanoparticles.), ZAad1 (Anacardic acid loaded zein nanoparticles administered at 2.25 μg/kg) and ZAad2 (Anacardic acid loaded zein nanoparticles administered at 112.5 μg/kg) treated for 7-days Black arrows indicate the thickness of gastric mucosa growth and red arrow indicates hemorrhagic point.
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