Effects of vildagliptin, metformin, and combination of vildagliptin and metformin on metabolic parameters (n = 11/group).

<p>*<i>P</i><0.05 vs. NDV, ^†<i>P</i><0.05 vs. HFDV.</p

Effects of vildagliptin, metformin, and combined drugs on cardiac mitochondrial function and morphology.

<p>(A) Mitochondrial ROS production was increased in ischemic area of NDV and HFDV, Mitochondrial ROS production was higher in HFDV than NDV, and all treatments reduced mitochondrial ROS production. *p<0.05 vs. remote area, ^†p<0.05 vs. ischemic area of NDV, n = 5/group. (B) Mitochondrial membrane depolarization was found in ischemia area of NDV and HFDV, all treatment prevented mitochondrial membrane depolarization. *p<0.05 vs. remote area of NDV, n = 5/group. (C) An absorbance was decreased in ischemic area of NDV and HFDV. The reduction of absorbance was greater in HFDV than NDV, and all treatments prevented mitochondrial swelling, *p<0.05 vs. remote area of NDV, n = 5/group. (D–M) Cardiac mitochondrial morphology</p

Effects of vildagliptin, metformin, combined drugs on arrhythmia, mortality rate, and phosphorylation of Cx43 level.

<p>(A) Combined drugs reduced arrhythmia score in HFD rats.*p<0.05 vs. HFDV, n = 11/group. (B) Combined drugs delayed time to the 1^st VT/VF onset in HFD rats. *p<0.05 vs. HFDV, n = 11/group. (C) Mortality rate was higher in HFDV, and combined drugs reduced mortality rate in both ND and HFD rats. *p<0.05 vs. NDV, ^†p<0.05 vs. HFDV, n = 11/group. (D) Combined drugs increased p-Cx43 in HFD rats. *p<0.05 vs. HFDV, n = 5/group.</p

Effects of vildagliptin, metformin, and combined drugs on infarct size, Bax, and Bcl-2 expression.

<p>(A) Infarct size was increased in HFDV, and all treatments reduced infarct size in both ND and HFD rats. *p<0.05 vs. NDV, ^†p<0.01 vs. HFDV, n = 6/group. (B) Representative images showing TTC staining for infarct size determination. (C) Bax expression was increased in HFDV, and all treatments reduced Bax expression in HFD rats. *p<0.05 vs. NDV, ^†p<0.05 vs. HFDV, n = 5/group. (D) Bcl-2 expression was decreased in HFDV, and all treatments increased Bcl-2 expression in HFD rats. *p<0.05 vs. NDV, ^†p<0.05 vs. HFDV, n = 5/group.</p

Effects of HFD consumption, vildagliptin, metformin, and combined drugs on HRV and echocardiographic parameters.

<p>(A) The LF/HF ratio was increased at week 8^th and week 12^thof HFD consumption.*p<0.05 vs. baseline, n = 11/group. (B) Vildagliptin, metformin, and combined drugs reduced the LF/HF ratio in HFD rats. *p<0.05 vs. NDV, ^†p<0.05 vs. HFDV, n = 11/group, (C) %FS was decreased after 12 weeks of HFD consumption.*p<0.05 vs. ND, n = 11/group. (D) LVEF was decreased after 12 weeks of HFD consumption.*p<0.05 vs. ND, n = 11/group. (E) Vildagliptin, metformin, and combined drugs increased %FS in HFD rats. *p<0.05 vs. HFDV, n = 11/group. (F) Vildagliptin, metformin, and combined drugs increased LVEF in HFD rats. *p<0.05 vs. HFDV, n = 11/group.</p

Effects of vildagliptin, metformin, and combination of vildagliptin and metformin on cardiac function at the end of Reperfusion (n = 11/group).

<p>*<i>P</i><0.05 vs. NDV, ^†<i>P</i><0.05 vs. HFDV.</p

Effects of metformin, vildagliptin, and combination of vildagliptin and metformin on cardiac function before I/R injury (n = 11/group).

<p>*<i>P</i><0.05 vs. NDV, ^†<i>P</i><0.05 vs. HFDV.</p

Effects of vildagliptin, metformin, and combined drugs on intracellular calcium regulation.

<p>(A) Intracellular diastolic calcium was increased in HFDV. All treatments reduced intracellular diastolic calcium in HFD rats. (B) Calcium transient amplitude was decreased in HFDV. All treatments improved calcium transient amplitude in HFD rats. (C) Calcium transient decay rate was reduced in HFDV. All treatments increased the calcium transient decay rate in HFD rats. (D) Representative calcium transient tracing for calcium transient parameters determination. *p<0.05 vs. baseline NDV, ^†p<0.01 vs. baseline HFDV, ^‡p<0.05 vs. HFDV with H₂O₂ n = 8 cells/group</p

Effects of HFD consumption on metabolic parameters at baseline and 12-week after HFD consumption.

<p>ND  =  normal diet, HFD  =  high-fat diet. *<i>P</i><0.05 vs. Baseline, ^†<i>P</i><0.05 vs. ND week 12.</p

Additional file 1 of Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients

Additional file 1: Fig. S1. Study protocol. Fig. S2. Absolute changes in LVEF (A), LF/HF ratio (B), plasma troponin I (C), plasma NT-proBNP (D), and cellular oxidative stress in peripheral blood mononuclear cells (E) at 2 weeks after completion of doxorubicin treatment in HER2-positive versus HER2-negative breast cancer patients. Table S1. Lists of eighty-five targeted plasma metabolomes and the chromatographic technique for each metabolome. Table S2. Patients’ characteristics at baseline. Table S3: Baseline plasma metabolome levels in HER2-positive versus HER2-negative breast cancer patients. Table S4. Plasma metabolome levels in HER2-positive breast cancer patients at baseline versus at 2 weeks after completion of doxorubicin treatment. Table S5. Plasma metabolome levels in HER2-negative breast cancer patients at baseline versus at 2 weeks after completion of doxorubicin treatment. Table S6. The top five plasma metabolomes that their alterations were significantly correlated with the changes in each cardiac parameter of HER2-positive and HER2-negative breast cancer patients at 2 weeks after completion of doxorubicin treatment