PhD Scientific Days 2020

Health Sciences Lectures

Toxicity of Carboplatin Increased to Granulopoiesis in OLETF Rats with CCK-1 Cholecystokinin Receptor Deficiency

Előadó neve

Beáta, Taskó, MSc

Előadó munkahelye

Facultaty of Medicine, Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36306922035

Előadó e-mail címe

pelles-tasko.beata@med.unideb.hu

Az előadás címe

Toxicity of Carboplatin Increased to Granulopoiesis in OLETF Rats with CCK-1 Cholecystokinin Receptor Deficiency

Szerző(k) neve és munkahelye

Beáta Taskó1, Krisztina Géresi2, Klára Benkő3, Attila Megyeri1, Zoltán Szilvássy1, Ilona Benkő1

1 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen
2 Laboratory of Clinical Immunology, Military Hospital, HDF- Medical Centre, Budapest
3 Department of Radiology, Clinical Centre, University of Debrecen, Debrecen

Szekció

Health Sciences Lectures

Language of the presentation

Hungarian

Section, first choice

Health Sciences

Section, second choice

Pharmaceutical Sciences

Összefoglaló szövege

Damage of granulopoiesis resulting neutropenia is the most frequent dose-limiting toxicity of cancer chemotherapy. Obesity is associated with lower phagocytic activity by macrophages and decreased resistance to some infections, which may be based on an affected granulopoiesis.
Our aim was to study whether obesity-associated changes of granulopoiesis can influence toxicity of anticancer drugs, namely carboplatin.
Granulopoiesis was studied in an obese animal model in OLETF rats with CCK1 receptor deficiency in comparison to their non-obese counterparts, LETO rats. Frequency of CFU-GM and total CFU-GM content of the femoral bone marrow characterize granulopoiesis. Special soft gel colony assay was used and bone marrow cells were cultured in the presence of carboplatin in vitro. Proglumide was iv. administered in vivo using 3 mg/kg dose.
Cholecystokinin, a gut-derived cytokine has a great role in control of appetite. The CCK receptor deficient OLETF rats became obese due to an excessive food intake. At first sight granulopoiesis was not differ in obese OLETF rats from the non-obese control LETO rats. However, testing vulnerability of granulocyte-macrophage progenitors (CFU-GM) by culturing them in the presence of carboplatin, we detected an increased toxicity to the CFU-GM progenitors obtained from OLETF rats dose-dependently compared to those from LETO rats. To evaluate whether the CCK receptor deficiency has a role we used pre-treatment in vivo for non-obese LETO rats by proglumide. Proglumide, a CCK antagonist resulted in similar increased sensitivity of the progenitor cells to toxic effects of carboplatin used in vitro.
Pharmacokinetic properties of anticancer drugs are often changed in obese patients however our results showed functional disorders of the target cells which responsible for production of mature macrophages. Increased toxicity of carboplatin to these progenitors results in more serious neutropenia with increased risk for life-threatening infections. As the CCK antagonist proglumide pre-treatment had similar effect on toxicity of carboplatin in non-obese LETO rats than the obese CCK deficient OLETF rats showed that cholecystokinin receptors are found on CFU-GM cells and they may have a role at least partly in increased myelotoxicity of anticancer drugs in obesity. Supported by GINOP2.3.4-15-2016-00002, NKFIH-1150-6/2019

Additional Information

EFOP-3.6.3-VEKOP-16-2017-0009

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4724

Start

11:05

End

11:20

Authors (legacy)

Beáta Taskó1, Krisztina Géresi2, Klára Benkő3, Attila Megyeri1, Zoltán Szilvássy1, Ilona Benkő1

1 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen
2 Laboratory of Clinical Immunology, Military Hospital, HDF- Medical Centre, Budapest
3 Department of Radiology, Clinical Centre, University of Debrecen, Debrecen