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2018-04-01 - Colloque/Présentation - poster - Anglais - 1 page(s) (A publier)

Maroil Dorian , Delsinne Virginie , Tagliatti Vanessa , "Metabonomic study of the hypothyroidism effect of sunitinib, a multiple inhibitor of tyrosine kinase receptors, by metabonomic approach in the rat." in 15 International Youth School-Conference "Magnetic resonance and its applications - Spinus-2018, Saint-Pétersbourg, Russie, 2018

  • Codes CREF : Médecine pathologie humaine (DI3300)
Texte intégral :

Abstract(s) :

(Anglais) Exploration of the hypothyroidic effect of Sunitinib, a tyrosine kinase receptor inhibitor, by metabolomic approach, in the rat Renal cell carcinoma is one of the most common and deadly cancer. This cancer suffers of an extremely poor prognosis due to its low survival rate in the long term and the incidence of metastasis. To date, there is no successful treatment although a multi-targeted receptor tyrosine kinase inhibitor, Sunitinib, gives significant results thanks to a strong antiangiogenic activity blocking the tumor development. Among the numerous side effects, some (hypertension, hypothyroidism and feet/hands syndrome) are correlated with an improved efficcacy of treatment in patients presenting those adverse effects. It is therefore mandatory to understand the cellular mechanisms of this Sunitinib-induced hypothyroidism, not yet clarified today, in order to establish the link between treatment efficacy and such a side effect. In order to obtain an overview of the overall changes induced by Sunitinib, the use of metabonomic seems to be the best choice. Indeed, this recent approach allows to establish the complete metabolic profiles of an individual from his biofluids. These profiles are obtained from spectroscopic techniques combined to multivariate data analysis. The main objectives of this work was first to establish a metabonomic urinary signature of an animal model of hypothyroidism induced by exposure to propyl-thiouracil and, next, to compare this signature with the metabonomic profile of animals daily exposed to pharmacological doses of Sunitinib. Finally, this study also tried to assess the contribution of a pre-existing hypothyroidism on the effects of Sunitinib. During the experimental study, several physiological parameters were also measured. The metabonomic signature of propyl-thiouracil -induced hypothyroidism showed significant decreases in the activity of the Krebs cycle and in the urinary excretion of taurine. These changes were also observed in rats with normal thyroid function when chronically exposed to Sunitinib demonstrating the hypothyroidian effect of this drug. Similar changes were finally recorded in animals with pre-existing hypothyroidism and exposed to Sunitinib, although at a lesser extent. Keywords: Metabonomic, Sunitinib, hypothyroidism