Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin

Abstract

ABSTRACT.Cisplatin is an effective antineoplastic drug. However, it provokes considerable collateral effects, including genotoxic and clastogenic activity. It has been reported that a diet rich in glutamine can help inhibit such collateral effects. We evaluated this activity in 40 Swiss Glutamine chemoprevention in vivo mice, distributed into eight experimental groups: G1 -Control group (PBS 0.1 mL/10g body weight); G2 -cisplatin group (cisplatin 6 mg/kg intraperitoneally); G3, G4, G5 -glutamine groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally); G6, G7, G8 -Pre-treatment groups (glutamine at 150, 300, and 600 mg/kg, respectively; orally and cisplatin 6 mg/kg intraperitonially). For the micronucleus assay, samples of blood were collected (before the first use of the drugs at T0, then 24 (T1) and 48 (T2) hours after the first administration). For the comet assay, blood samples were collected only at T2. The damage reduction percentages for the micronucleus assay were 90.0, 47.3, and 37.3% at T1 and 46.0, 38.6, and 34.7% at T2, for G6, G7, and G8 groups, respectively. For the comet assay, the damage reduction percentages were 113.0, 117.4, and 115.0% for G6, G7, and G8, respectively. We conclude that glutamine is able to prevent genotoxic and clastogenic damages caused by cisplatin.

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.…”

“…In addition to the ability to reduce commercial chemotherapeutics effects, IR-01 also has a pharmacophoric radical in its structure, which could increase the antioxidant defenses in non-injured cells. This hypothesis is supported by Bianchi and Antunes (1999) , Albertini and Ruiz (2001) , Antunes and Bianchi (2004) , and Oliveira et al. (2013) , who reported that cells that have DNA lesions are deficient in antioxidant defenses.…”

Evaluation of the antimutagenic activity and mode of action of the fructooligosaccharide inulin in the meristematic cells of Allium cepa culture

“…This study used pretreatment, simultaneous simple, simultaneous with pre-incubation, and post-treatment protocols to evaluate the antimutagenicity of inulin. The simultaneous simple protocol indicated the desmutagenic and bioantimutagenic activity, the simultaneous with pre-incubation protocol indicated the desmutagenic activity, and the pre-and post-treatment protocols indicated preferably a biomutagenic activity (Ferguson, 1994;Flagg et al, 1995;Antunes and Araújo, 2000;De Flora and Ferguson, 2005;Oliveira et al, 2006Oliveira et al, , 2007Oliveira et al, , 2009Oliveira et al, , 2013bda Silva et al, 2013).…”

Antigenotoxic and antimutagenic effects of glutamine supplementation on mice treated with cisplatin

“…This was revealed by the damage reduction percentages of 115.05, 119.06, and 114.38% for the glutamine doses of 150, 300, and 600 mg/kg bw, respectively. Oliveira et al (2013) also tested the chemopreventive activity of glutamine using the same assays but with a different protocol. The authors also observed no dose-dependent response, but similar DR% values were observed for the comet assay.…”