Premedication with pioglitazone prevents doxorubicin-induced left ventricular dysfunction in mice

摘要

Pio pretreatment partially prevented DOX-induced LV dysfunction in the acute phase (day 7), but not in the hyperacute phase (day 1). a Diagram showing the treatment course of each group. For the hyperacute and acute phases, mice were divided into 3 groups. Vehicle mice were fed a standard diet and treated with vehicle instead of DOX. DOX mice were fed a standard diet and treated with a single DOX bolus (15 mg/kg of body weight [BW]) on day 0. Pio + DOX mice were orally administered with Pio (0.02% [wt/wt]) from day − 5 as premedication, and then treated with a DOX bolus on day 0. All measurements were acquired and hearts were excised on both day 1 (hyperacute phase) and day 7 (acute phase). The horizontal open arrows represent standard diet intake, and the horizontal closed arrow indicates Pio intake. The vertical arrows indicate treatment with vehicle or DOX. b Kaplan-Meier survival curves of Vehicle (n = 15, black broken line), DOX (n = 15, blue line), or Pio + DOX mice (n = 15, red line). c Representative echocardiographs of Vehicle (left panel), DOX (middle panel), and Pio + DOX (right panel) mice. d, e, f, g, h Summary data of LVEDD, LVESD, %FS, HR, and LV wall thickness. Day 1: Vehicle (open upward triangles, n = 10), DOX (open circles, n = 10), and Pio + DOX (closed circles, n = 10). Day 7: Vehicle (n = 25), DOX (n = 26), and Pio + DOX (n = 25). i, j, k Summary data of BW, LV/BW, and lung/BW. Data are shown as means ± SEs. *P < 0.05 vs. Vehicle, †P < 0.05 vs. DOX. DOX, doxorubicin; Pio, pioglitazone; LV, left ventricle; LVEDD, LV end-diastolic diameter, LVESD, LV end-systolic diameter; %FS, percent fractional shortening