PMID- 29623860
OWN - NLM
STAT- MEDLINE
DCOM- 20190605
LR  - 20190605
IS  - 2212-4063 (Electronic)
IS  - 1871-529X (Linking)
VI  - 18
IP  - 3
DP  - 2018
TI  - Adenosine and Adenosine 5'-triphosphate Catabolism in Systemic Blood as a 
      Potential Biomarker for Doxorubicin Cardiotoxicity in an Experimental Rat Model 
      in vivo.
PG  - 224-233
LID - 10.2174/1871529X18666180406125225 [doi]
AB  - BACKGROUND: Previous studies have shown that metabolism of adenosine 
      5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for 
      cardiovascular toxicity. OBJECTIVE: To investigate the acute effect of high dose 
      of doxorubicin (DOX) on adenosine and ATP catabolism in systemic blood in vivo. 
      METHOD: Sprague Dawley (SD) rats were each given either 10 mg/kg of DOX (n = 8) 
      or normal saline (1 mL/kg, n = 11) twice daily for 4 doses by subcutaneous (sc) 
      injection. Blood samples were collected sequentially for up to 6 hours for 
      measuring circulating concentrations of ATP, adenosine and their metabolites. 
      Hemodynmic recording was obtained continuously after the last injection. The 
      difference in response between groups was considered significant at p < 0.05 
      (t-test). RESULTS: Diastolic blood pressure (DBP) was significantly lower in the 
      DOX treated rats than in the control before the final injection (87 +/- 12 vs. 104 
      +/- 11 mmHg, p < 0.05). Blood pressure fell gradually after the last injection and 
      the decrease was significantly greater in the DOX treated group (p < 0.05). 
      Plasma concentration of adenosine was significantly lower in the DOX treated 
      group. In contrast, plasma concentrations of uric acid and hypoxanthine, as well 
      as Red Blood Cell (RBC) concentrations of AMP, were significantly higher (p < 
      0.05). CONCLUSION: Acute cardiotoxicity induced by DOX may be measured by the 
      increased breakdown of ATP to AMP in the RBC and also breakdown of adenosine to 
      hypoxanthine and uric acid in plasma.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Yeung, Pollen K
AU  - Yeung PK
AD  - Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of 
      Medicine, Faculties of Health Professions and Medicine, Dalhousie University, 
      Halifax, NS, Canada.
FAU - Purcell, Chad
AU  - Purcell C
AD  - Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of 
      Medicine, Faculties of Health Professions and Medicine, Dalhousie University, 
      Halifax, NS, Canada.
FAU - Akhoundi, Fatemeh
AU  - Akhoundi F
AD  - Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of 
      Medicine, Faculties of Health Professions and Medicine, Dalhousie University, 
      Halifax, NS, Canada.
FAU - Agu, Remigius U
AU  - Agu RU
AD  - Biopharmaceutics and Drug Delivery Laboratory, College of Pharmacy, Faculty of 
      Health Professions, Dalhousie University, Halifax, NS, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Cardiovasc Hematol Disord Drug Targets
JT  - Cardiovascular & hematological disorders drug targets
JID - 101269160
RN  - 0 (Biomarkers)
RN  - 0 (Polyphosphates)
RN  - 80168379AG (Doxorubicin)
RN  - K72T3FS567 (Adenosine)
RN  - NU43IAG5BC (triphosphoric acid)
SB  - IM
MH  - Adenosine/*metabolism
MH  - Animals
MH  - Biomarkers/*blood
MH  - Cardiotoxicity/*etiology/pathology
MH  - Disease Models, Animal
MH  - Doxorubicin/*adverse effects
MH  - Male
MH  - Polyphosphates/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - ATP
OT  - Adenosine
OT  - cardiotoxicity
OT  - catabolism
OT  - doxorubicin
OT  - rats.
EDAT- 2018/04/07 06:00
MHDA- 2019/06/06 06:00
CRDT- 2018/04/07 06:00
PHST- 2017/12/14 00:00 [received]
PHST- 2018/02/16 00:00 [revised]
PHST- 2018/04/01 00:00 [accepted]
PHST- 2018/04/07 06:00 [pubmed]
PHST- 2019/06/06 06:00 [medline]
PHST- 2018/04/07 06:00 [entrez]
AID - CHDDT-EPUB-89579 [pii]
AID - 10.2174/1871529X18666180406125225 [doi]
PST - ppublish
SO  - Cardiovasc Hematol Disord Drug Targets. 2018;18(3):224-233. doi: 
      10.2174/1871529X18666180406125225.