Chemopreventive activity of phenylalanine against damage mutagenic prompted by the acute administration of cyclophosphamide in pregnant and non-pregnant mice using the micronucleus test

Abstract

RESUMO: "Atividade quimiopreventiva da fenilalanina contra danos mutagênicos pela administração aguda de ciclofosfamida em ratas grávidas e não grávidas, utilizando o teste do micronúcleo". A presente pesquisa teve por objetivo avaliar a capacidade quimiopreventiva da fenilalanina. Utilizou-se um lote de fêmeas prenhes e não prenhes divididas nos seguintes grupos experimentais: G1, PBS (0,1 mL/kg p.c.); G2, ciclofosfamida (35 mg/kg p.c.-i.p.); G3, fenilalanina (150 mg/kg p.c.-v.o.) e G4, fenilalanina (300 mg/kg p.c. -v.o.) e G5 (150 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida); G6, (300 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida). As coletas de sangue periférico foram realizadas em T0, antes da administração de qualquer substância teste e/ou veículos, e igualmente em T24 e T48, onde as coletas foram realizadas respectivamente 24 e 48 h após a administração da ciclofosfamida. Em uma análise geral verificou-se que, para o grupo de fêmeas não prenhes, a avaliação da antimutagenicidade demonstrou porcentagens de redução de danos de 57,24% e 31,64% para G5 e G6, respectivamente, em T24, e 29,32% e 24,13% para G5 e G6, respectivamente, em T48. Nos animais prenhes a antimutagenicidade de 24 h demonstrou eficiência quimiopreventiva apenas para a menor dose (G5) e as porcentagens de redução de danos foram de 43,25% em G5 e 18,47% em G6. No momento T48 as porcentagens de redução de danos foram de 44,67% e 37,76% para G5 e G6, respectivamente.Unitermos: Fenilalanina, antigenotóxico, ciclofosfamida, prenhes.ABSTRACT: This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24% and 31.64% for G5 and G6, respectively, at T24, and 29.32% and 24.13% for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25% in G5 and G6 at 18.47%. At T48 the harm-reduction percentages were 44.67% and 37.76% for G5 and G6, respectively.

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

“…Although there are significant differences in the frequency of micronuclei between the negative control group and the groups treated with IR-01, Vaz et al (2016) describes that this isolated fact does not necessarily imply in toxicogenetic damage. Also, according to the results observed in other experiments from our research group ( Oliveira et al , 2009a , 2013 ; Mauro et al. , 2010 ; Pesarini et al , 2014 ; Navarro et al , 2015 ), the baseline frequency of micronuclei can be greater than the frequency observed for the animals treated with IR-01 in the present study.…”

Effects of phenylalanine on reproductive performance and teratogenesis in mice

“…Additionally, the lowest supplementation dose of phenylalanine presented the highest antimutagenic activity and, consequently, reduced damage to a greater extent. There was no dose-response curve for the doses tested (Mauro et al, 2010).…”

“…No reports were found in the literature about the ability of phenylalanine to prevent teratogenesis. There is only one report of phenylalanine chemoprevention related to an alkylating agent, which is also from our group (Mauro et al, 2010). We previously studied 2 groups of female mice, pregnant and not pregnant, treated with the same doses and followed the same procedures used in the present study.…”

“…Support for such antioxidant activity was suggested by Degáspari and Waszczynskyj (2004), who reported that flavonoids are formed from a combination of synthesized phenylalanine derivatives (metabolic via chiquimic acid) and acetic acid. Thus, phenylalanine supplementation is an effective dietary measure for preventing damage to DNA caused by clastogenic agents; and can be evaluated by the micronucleus test (Mauro et al, 2010).…”

Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

“…Regarding the results for mutagenicity in Preadmet software, all screened and reference molecules were classified as mutagenic. Even showing mutagenicity, where elimination of molecules for this reason would be premature, studies with rats have shown that a mutagenic molecule when administered in combination with an antimutagenic (chemopreventive) agent may cause suppression of the mutagenic action [ 48 , 49 ].…”