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

Araújo, Jennifer Thayanne Cavalcante de; Lima, Laís Aragão; Vale, Everton Pantoja; Martín-Pastor, Manuel; Lima, Ramille Araújo; Silva, Paulo Goberlânio de Barros; Sousa, Francisco Fábio Oliveira de

doi:10.1016/j.toxrep.2020.08.024

Cited by 10 publications

(5 citation statements)

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“…In our ndings, the stomach weight of the AaZNp increased in comparison to the negative and standard control groups. A similar result was also observed when a short-term subacute toxicity protocol testing the same nanoformulation was analyzed (Araújo et al 2020). Harlita et al (2016) reported that the mean mass of the stomachs did not exhibit any signi cant increase or decrease.…”

Section: Discussionsupporting

confidence: 75%

“…Although Anacardium occidentale and its phytochemicals are broadly used, few studies access their toxicity, limiting their extensive use (Carvalho et al 2011;Anand et al 2015). A short-term genotoxicity and toxicity assessment was previously performed (Araújo et al 2020). Nonetheless, a subacute topic and systemic toxicity evaluation are mandatory to support its clinical usage, expanding the potential applications of zein nanoparticles containing anacardic acid.…”

Section: Introductionmentioning

confidence: 99%

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Oral mucosa and subacute systemic toxicity of anacardic acid loaded-zein nanoparticles

de Souza,

Brasileiro,

Lima

et al. 2024

Preprint

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Anacardic acid, a bioactive phytochemical extracted from cashew shell liquid of Anacardium occidentale, is a promising oral antimicrobial agent, lacking complete toxicity evaluation. This study aimed to evaluate the oral mucosal and systemic toxicity of zein nanoparticles containing anacardic acid in vivo. Oral (gavage) and topical administration on oral mucosa were performed in mice (female c57bl/6j) over 30 days, distributed in four groups: Negative control - sterile saline solution 0.89%; Standard Group – chlorhexidine gluconate 0.12%; Group AaZNp – anacardic acid loaded-zein nanoparticles (9.337 µg/mL) and Group BZNp – blank zein nanoparticles. Weight variation, relative organs weight, and thickness of target organs were analyzed. Subepithelial inflammation frequency (%) was determined. ANOVA/Tukey test and chi-square/Fisher’s exact tests were used (p < 0.05). Groups AaZNp (-4.2 ± 1.49 g) and BZNp (-4.00 ± 1.30 g) showed the highest weight loss; although without significant difference in kidneys, lungs, liver, and spleen weights. Groups AaZNp (0.16 ± 0.01 g) and BZNp (0.16 ± 0.02 g) presented lower cardiac mass than the negative (0.21 ± 0.01 g) and standard (0.22 ± 0.02 g) (p = 0.045) groups. Ventral tongue epithelium thickness of the negative control (3250 ± 439 µm) was significantly lower than BZNp treated (8650 ± 1079 µm) (p = 0.001); Jugal epithelial thickness was lower in AaZNp and BZNp than Standard Group (p < 0.001), while the thickness of gingival epithelium was lower in the negative control (134 ± 13 µm) than the other groups (p = 0.001). There were no significant signs of inflammatory infiltrate. The administration of AaZNp and BZNp caused a reduction in the cardiac mass without showing other signs of oral mucosal or systemic toxicity.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Oral mucosa and subacute systemic toxicity of anacardic acid loaded-zein nanoparticles

de Souza,

Brasileiro,

Lima

et al. 2024

Preprint

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“…Cashew nut ( Anacardium occidentale L.) is described by Merian as a vermifuge. Components extracted from the nut, such as anacardic acid, have an anti- Trypanosoma cruzi effect [ 136 , 137 ], as well actions against echinococcosis [ 138 , 176 ] and a larvicidal and antimicrobial effect [ 177 ]. The ethanolic extract of the bark of this plant showed an in vitro anthelmintic effect against the parasite Onchocerca ochengi [ 176 ].…”

Section: Resultsmentioning

confidence: 99%

Female naturalists and the patterns of suppression of women scientists in history: the example of Maria Sibylla Merian and her contributions about useful plants

Mariath

Baratto

2023

J Ethnobiology Ethnomedicine

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Background This work reunites many women naturalists who registered knowledge about native flora in scientific expeditions around the globe between the seventeenth and nineteenth centuries. Since male naturalists are more recognized in this period of time, we aimed to list female naturalists that published plant descriptions and observations, focusing on the work of Maria Sibylla Merian and to analyze her trajectory as an example to discuss the patterns of the suppression of women scientists. A second aim was to inventory the useful plants described in Maria Sibylla’s Metamorphosis Insectorum Surinamensium and find pharmacological evidence about the traditional uses described for those plants cited as medicinal and toxic. Methods A survey of female naturalists was carried out by searching information in Pubmed, Scielo, Google Scholar and Virtual Health Library. Once Maria Sibylla published her book Metamorphosis Insectorum Surinamensium by her own, without male co-authors, and also this book is one of the only to have text and illustrations altogether and there are reports indicating information on useful plants in this work, she and her book were chosen as subject of this research. All the information was tabulated by dividing the plants into food, medicinal, toxic, aromatic or other uses. Finally, with the combinations of the scientific name of medicinal and toxic plants with information about their popular uses, a search was carried out in databases in order to indicate current pharmacological studies that reported evidences about the traditional uses described. Results We found 28 women naturalists who participated in scientific expeditions or trips, or in a curiosity cabinet, or who were collectors of Natural History between the seventeenth and nineteenth centuries. All these women illustrated botanical species and/or recorded their everyday or medicinal use or reported their observations in the form of a published work, letters or diaries. Also, the trajectory of Maria Sibylla Merian revealed that her scientific relevance has been neglected from the eighteenth century by mechanisms of suppression, most of the time by male depreciation, which can be seen as a pattern for suppression of women in science. However, Maria Sibyllas’ contributions have been valued again in the twenty-first century. In Maria Sibylla’s work, 54 plants were identified, 26 of them used for food, 4 of them aromatic, 8 medicinal, 4 toxic and 9 other uses. Conclusion This study evidences that there are female naturalists whose work could be an important source for ethnopharmacological studies. Researching about women scientists, talking about them and highlighting the gender bias present in the scientific academy about the way the history of science is told is essential for the construction of a more diverse and richer scientific academy. The traditional use of 7 of 8 medicinal plants and 3 of 4 toxic plants reported was correlated with pharmacological studies, highlighting the importance of this historical record and its potential to direct strategic research in traditional medicine.

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“…AA and its derivatives are well-known for their therapeutic applications ranging from antitumor, antibacterial, antioxidant, anticancer, and so forth [ 32 ]. Many studies have shown that AA has no serious toxic and side effects in a certain concentration range [ 33 , 34 ]. Thus, the findings of this study can provide a new candidate drug for the prevention and treatment pathological cardiac hypertrophy caused by neurohumoral factor disorder in clinical.…”

Section: Discussionmentioning

confidence: 99%

JNK signaling-dependent regulation of histone acetylation are involved in anacardic acid alleviates cardiomyocyte hypertrophy induced by phenylephrine

et al. 2021

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Cardiac hypertrophy is a complex process induced by the activation of multiple signaling pathways. We previously reported that anacardic acid (AA), a histone acetyltransferase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the related upstream signaling events remained unknown. The mitogen-activated protein kinase (MAPK) pathway is an important regulator of cardiac hypertrophy. In this study, we explored the role of JNK/MAPK signaling pathway in cardiac hypertrophy induced by PE. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE in vitro. This study showed that p-JNK directly interacts with HATs (P300 and P300/CBP-associated factor, PCAF) and alters H3K9ac. In addition, both the JNK inhibitor SP600125 and the HAT inhibitor AA attenuated p-JNK overexpression and H3K9ac hyperacetylation by inhibiting P300 and PCAF during PE-induced cardiomyocyte hypertrophy. Moreover, we demonstrated that both SP600125 and AA attenuate the overexpression of cardiac hypertrophy-related genes (MEF2A, ANP, BNP, and β-MHC), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiomyocyte hypertrophy. In particular, AA inhibits the effects of JNK signaling on HATs-mediated histone acetylation, and could therefore be used to prevent and treat pathological cardiac hypertrophy.

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

Abstract: Graphical abstract

Cited by 10 publications

References 60 publications

Oral mucosa and subacute systemic toxicity of anacardic acid loaded-zein nanoparticles

Oral mucosa and subacute systemic toxicity of anacardic acid loaded-zein nanoparticles

Female naturalists and the patterns of suppression of women scientists in history: the example of Maria Sibylla Merian and her contributions about useful plants

JNK signaling-dependent regulation of histone acetylation are involved in anacardic acid alleviates cardiomyocyte hypertrophy induced by phenylephrine

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