Study of the potential adverse effects caused by the dermal application of Dillenia indica L. fruit extract standardized to betulinic acid in rodents

Autor:	Luiz Alberto Kanis, Flavia Fernandes, Daniel Martins, Ana Carolina da Silva Carvalho, Karina Valerim Teixeira Remor, Aline Daiane Schlindwein, Gustavo Silveira da Silva, Alexandre S. Hilel, Maicon Roberto Kviecinski
Rok vydání:	2019
Předmět:	Acute effects Physiology Positive control Pharmacology Dillenia Pathology and Laboratory Medicine Toxicology chemistry.chemical_compound Mice White Blood Cells 0302 clinical medicine Mathematical and Statistical Techniques Animal Cells Betulinic acid Dilleniaceae Red Blood Cells Medicine and Health Sciences Skin Multidisciplinary Photosensitizing Agents biology Statistics Eukaryota Plants Body Fluids Diarrhea Blood 030220 oncology & carcinogenesis Physical Sciences Medicine medicine.symptom Cellular Types Anatomy Pentacyclic Triterpenes Research Article Science Immune Cells Immunology Dermatology Administration Cutaneous Research and Analysis Methods Fruits 03 medical and health sciences Signs and Symptoms Diagnostic Medicine medicine Animals Humans Betulinic Acid Statistical Methods Adverse effect Clobetasol Analysis of Variance Blood Cells Toxicity business.industry Plant Extracts Organisms Biology and Life Sciences Cell Biology biology.organism_classification Skin Irritancy Tests Triterpenes Rats chemistry Erythema Initial phase Fruit Mouse skin Leukocytes Mononuclear business 030217 neurology & neurosurgery Mathematics
Zdroj:	PLoS ONE PLoS ONE, Vol 14, Iss 5, p e0217718 (2019)
ISSN:	1932-6203
Popis:	This study aimed to evaluate the potential adverse effects of the dermal administration of Dillenia indica Linnaeus (D. indica) fruit extract in healthy rodents; the extract was standardized to betulinic acid. In the initial phase, the acute effects were evaluated on the skin application site of a single extract dose. A skin irritation test was performed in male Wistar rats (n = 8/group) receiving the extract (50-150 mg/mL) with betulinic acid (0.5-1.5%, respectively). A photosensitivity test was performed in male BALB/c mice (n = 6/group) receiving the extract (150 mg/mL). Afterwards, other BALB/c mice (n = 20, male:female, 1:1) were used to assess the systemic alterations caused by 14 daily repeated doses (150 mg/mL) by monitoring the effects on mortality, body morphology, behavior, nutrition status, neuromotor reactions, organ morphology and weight, and blood tests. At this time, 0.5 mg/mL clobetasol was used as the positive control. The skin irritation index suggested that negligible skin irritation had occurred, even when the extract was applied to the rat skin at 150 mg/mL. However, the extract acted as a photosensitizer on mouse skin, showing a photosensitizing activity close to that of 10 mg/mL 5-methoxypsoralen. Repeated doses caused no mouse mortality, aggressiveness, piloerection, diarrhea, convulsions, neuromotor alterations or nutrition status changes. The mouse organ weights did not change, and the mice did not have alterations in their blood compositions. Clobetasol caused a reduction in the mononuclear leukocyte numbers. In general, the data suggest that the extract was safe in healthy rodents but indicate that caution should be taken with the photosensitizing activity; in addition, this activity should be further explored as it may be useful for phototherapeutic drug development.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63dd011a656d29dd3f4d7fc5149875ca https://pubmed.ncbi.nlm.nih.gov/31150479 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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