| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-88 |
Sentence |
denotes |
High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity. |
| T2 |
89-222 |
Sentence |
denotes |
Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. |
| T3 |
223-341 |
Sentence |
denotes |
Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. |
| T4 |
342-528 |
Sentence |
denotes |
This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. |
| T5 |
529-752 |
Sentence |
denotes |
In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. |
| T6 |
753-1015 |
Sentence |
denotes |
A LD(10) dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. |
| T7 |
1016-1180 |
Sentence |
denotes |
Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. |
| T8 |
1181-1744 |
Sentence |
denotes |
Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-alpha, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9+/-14.0 nmol/min/g heart in ND versus 400.2+/-11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-alpha2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. |
| T9 |
1745-1859 |
Sentence |
denotes |
Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. |
| T10 |
1860-2097 |
Sentence |
denotes |
In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3 pathway. |
