Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncotarget Année : 2018

Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice

Résumé

Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients' quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known. Chronic injections of DZNep were performed intraperitoneally in male NMRI mice (2 mg/kg; i.p.; three times per week) during 8 weeks. A follow-up of body weight was assessed during all experiments. Histological analysis were performed on several organs. EZH2 expression and H3K27me3 were assayed by western-blot. Several behavioral tests were performed during treatment and 2 weeks after. A particular focus was made on spontaneous locomotor activity, cognitive functions (spontaneous alternation and recognition memory), and anxiety- and depression-related behavior. Hematological modifications were also assessed. Chronic DZNep treatment transiently reduced animal growth. It had no effect on most organs but provoked a reversible splenomegaly, and persistent testis reduction and erythropoiesis. DZNep administration did not alter animal behavior. In conclusion, this study is encouraging for the use of DZNep for cancer treatment. Indeed, it has no effect on animal behavior, conferring an advantageous safety, and induces irreversible side effects limited on testis which are unfortunately found in most chemotherapy treatments.
Fichier principal
Vignette du fichier
25062-1000247-4-PB.pdf (2.08 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01796395 , version 1 (03-05-2019)

Identifiants

Citer

Eva Lhuissier, Juliette Aury-Landas, Valentine Bouët, Céline Bazille, Yohann Repesse, et al.. Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice. Oncotarget, 2018, 9 (29), pp.20698 - 20708. ⟨10.18632/oncotarget.25062⟩. ⟨hal-01796395⟩
76 Consultations
53 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More