Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.

Autor:	de Jesus LCL; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil., Soares RP; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil., Moreira VR; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil., Pontes RL; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil., Castelo-Branco PV; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil., Pereira SRF; Laboratório de Genética e Biologia Molecular, Departamento de Biologia, Universidade Federal do Maranhão, Cidade Universitária Dom Delgado, São Luís, Maranhão, Brazil silmaregina@yahoo.com.br.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Aug 27; Vol. 62 (9). Date of Electronic Publication: 2018 Aug 27 (Print Publication: 2018).
DOI:	10.1128/AAC.00456-18
Abstrakt:	Meglumine antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that meglumine antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by meglumine antimoniate. For that, mice ( n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg meglumine antimoniate via intraperitoneal (i.p.) route. Furthermore, mice ( n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg meglumine antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving meglumine antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with meglumine antimoniate. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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