Medicinal Chemistry

DNA Damage and Cell Death Induced by Crude Extract of the Orchid Oncidium flexuosum Sims

Abstract

Mônica Piacentini Luizon, Caroline Santos Oliveira, Danielly Kathe Zaqueo, Jaqueline Aparecida Oliveira, Gustavo Ligieri Pereira do Prado, Renata Barbieri, Fernanda Oliveira Gaspari de Gaspi, João Ernesto de Carvalho, Elaine Cristina Mathias da Silva-Zacarin, Camila Andréa Oliveira, Acácio Antônio Pigoso and Grasiela Dia

Oncidium flexuosum Sims. is an orchidwhose leaves are frequently used for therapeutic applications although its action mechanism is not exactly understood. So the aim of this study was investigate its effects in Wistar rat liver, kidney and bone marrow. For this purpose, twenty-five adult male Wistar rats were divided into five groups of 5 animals each: a control group receiving only water, a positive control receiving a mutagen compound and three groups treated for 15 days with 100, 250 or 500 mg/kg/day of a crude hydroalcoholic leaf extract of O. flexusosum Sims. No significant alterations were observed in –SH groups, MDA or catalase, showing that the extract does not induce hepatic oxidative damage. There was no evidence of kidney injury and hepatic function alteration (ALT). However, significant mitochondrial swelling was observed in the treated groups and is probably related to cell death induction observed in cells that displayed acidophilia, pyknosis and positive labeling with the TUNEL technique at higher concentrations of the extract. We demonstrated that the hepatotoxicity of the extract resulted from its ability to induce DNA and mitochondrial damage that arrests cells, leading to cell death, probably caused by the flavonoidsand tannins present in this extract.