PMID- 23993975
OWN - NLM
STAT- MEDLINE
DCOM- 20140106
LR  - 20181202
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 273
IP  - 1
DP  - 2013 Nov 15
TI  - Differential cardiotoxicity in response to chronic doxorubicin treatment in male 
      spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), 
      and Wistar Kyoto (WKY) rats.
PG  - 47-57
LID - S0041-008X(13)00362-1 [pii]
LID - 10.1016/j.taap.2013.08.012 [doi]
AB  - Life threatening complications from chemotherapy occur frequently in cancer 
      survivors, however little is known about genetic risk factors. We treated male 
      normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with 
      cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 
      12weeks of observation to test the hypothesis that genetic cardiovascular disease 
      would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight 
      loss, decreased systolic blood pressure, increased kidney weights, greater 
      cardiac and renal histopathologic lesions and greater mortality. SHHF showed 
      growth restriction, increased kidney weights and renal histopathology but no 
      effect on systolic blood pressure or mortality. SHHF had less severe cardiac 
      lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content 
      and arachidonic acid metabolites after acute DOX exposure as potential mediators 
      of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH 
      and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 
      isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF 
      and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased 
      after treatment in SHR. Genetic predisposition to heart failure superimposed on 
      genetic hypertension failed to generate greater toxicity compared with 
      hypertension alone. The relative resistance of DOX-treated SHHF males to the 
      cardiotoxic effects of DOX in the delayed phase despite progression of genetic 
      disease was unexpected and a key finding. Strain differences in arachidonic acid 
      metabolism may contribute to variation in response to DOX toxicity.
CI  - (c) 2013 Elsevier Inc. All rights reserved.
FAU - Sharkey, Leslie C
AU  - Sharkey LC
AD  - Veterinary Clinical Sciences Department, University of Minnesota, 1352 Boyd Ave, 
      St. Paul, MN 55108 USA. Electronic address: shark009@umn.edu.
FAU - Radin, M Judith
AU  - Radin MJ
FAU - Heller, Lois
AU  - Heller L
FAU - Rogers, Lynette K
AU  - Rogers LK
FAU - Tobias, Anthony
AU  - Tobias A
FAU - Matise, Ilze
AU  - Matise I
FAU - Wang, Qi
AU  - Wang Q
FAU - Apple, Fred S
AU  - Apple FS
FAU - McCune, Sylvia A
AU  - McCune SA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130828
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Cardiotoxins)
RN  - 0 (Troponin T)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 73836-78-9 (Leukotriene D4)
RN  - 80168379AG (Doxorubicin)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/blood
MH  - Animals
MH  - Arachidonic Acid/blood
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Cardiotoxins/*toxicity
MH  - Chromatography, High Pressure Liquid
MH  - Doxorubicin/*toxicity
MH  - Epoxide Hydrolases/metabolism
MH  - Genetic Predisposition to Disease
MH  - Heart Diseases/chemically induced/*genetics/*pathology
MH  - Kidney/drug effects/pathology
MH  - Leukotriene D4/blood
MH  - Male
MH  - Organ Size/drug effects
MH  - Rats
MH  - *Rats, Inbred SHR
MH  - *Rats, Inbred WKY
MH  - Troponin T/blood
MH  - Ventricular Function, Left/drug effects
OTO - NOTNLM
OT  - %FS
OT  - Arachidonic acid
OT  - BW
OT  - CYP
OT  - Cardiotoxicity
OT  - DHET
OT  - DOX
OT  - Doxorubicin
OT  - EET
OT  - Epoxyeicosatrienoic acid
OT  - HE
OT  - HETE
OT  - Hypertension
OT  - LTD4
OT  - LVIDd
OT  - LVIDs
OT  - SAL
OT  - SBP
OT  - SHHF
OT  - SHR
OT  - Soluble epoxide hydrolase
OT  - WKY
OT  - Wistar Kyoto rat
OT  - body weight
OT  - cTnT
OT  - cardiac troponin T
OT  - cytochrome P450
OT  - dihydroxyeicosatrienoic acid
OT  - doxorubicin
OT  - epoxyeicosatrienoic acid
OT  - hematoxylin and eosin
OT  - hydroxyeicosatetraenoic acid
OT  - left ventricular fractional shortening
OT  - left ventricular internal diameter in diastole
OT  - left ventricular internal diameter in systole
OT  - leukotriene D4
OT  - sEH
OT  - saline
OT  - soluble epoxide hydrolase
OT  - spontaneous hypertension heart failure rat
OT  - spontaneously hypertensive rat
OT  - systolic blood pressure
EDAT- 2013/09/03 06:00
MHDA- 2014/01/07 06:00
CRDT- 2013/09/03 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/07/28 00:00 [revised]
PHST- 2013/08/10 00:00 [accepted]
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2014/01/07 06:00 [medline]
AID - S0041-008X(13)00362-1 [pii]
AID - 10.1016/j.taap.2013.08.012 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Nov 15;273(1):47-57. doi: 
      10.1016/j.taap.2013.08.012. Epub 2013 Aug 28.