Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats

Figures & data

Table 1.  Effect of Dox, Pro and their combination on heart rate, ST segment, QT interval and T wave amplitude of rats ECG.

Groups	Heart rate (beats/min)	ST segment elevation (mV)	QT interval (msec)	T wave (mV)
Control	238 ± 13.46	0.24 ± 0.02	73.08 ± 2.63	0.53 ± 0.04
Pro	230 ± 14.93	0.2 ± 0.02	69.33 ± 2.67	0.52 ± 0.04
Dox	335 ± 11.21**	0.47 ± 0.04**	90.00 ± 3.33**	0.83 ± 0.06**
Dox + Pro	264 ± 13.90*	0.23 ± 0.02*	86.25 ± 3.24**	0.53 ± 0.05*

Data are expressed as mean ± SEM, n = 6.

Pro (70 mg/kg, orally) was given once daily for 10 consecutive days.

Dox (15 mg/kg, i.p.) was injected on the 7th day 1 h after Pro administration.

Analysis of the ECG waves was done 72 h after Dox injection.

Mean values were compared together using one-way ANOVA followed by Tukey–Kramer multiple comparisons test.

**Significantly different from the mean value of the control group (p < 0.05).

*Significantly different from the mean value of Dox-treated group (p < 0.05).

Figure 1.  Chart records showing ECG tracings; A: ECG for control group, B: ECG for Dox-treated group, C: ECG for (Pro)-treated group, D: ECG for (Dox + Pro)-treated group, and E: Electrocardiographic tracing of a control anesthetized rat infused with aconitine. Anesthesia was induced by urethane (1.8 g/kg, i.p.). Aconitine (2.5 µg/ml) was infused via jugular vein in a rate of (0.5 ml/min) till appearance of ventricular tachycardia (VT). Electrocardiograms were recorded from standard lead II limb leads. The sensitivity was 2 mV and chart speed was 50 mm/sec.

Figure 2.  Effect of Dox, Pro and their combination on the threshold dose of aconitine producing ventricular tachycardia in rats. Values represent the mean ± SEM of 6 rats/group. Pro (70 mg/kg, orally) was given once daily for 10 consecutive days. Dox (15 mg/kg, i.p.) was injected on the 7th day 1 h after Pro administration. Determination of the threshold dose of aconitine producing VT was done 72 h after Dox injection. Mean values were compared together using one-way ANOVA followed by Tukey–Kramer multiple comparisons test. ^$Significantly different from the mean value of the control group (p < 0.05). *Significantly different from the mean value of Dox-treated group (p < 0.05).

Table 2.  Effect of Dox, Pro and their combination on serum CK-MB, LDH and catalase activities and myocardial SOD activity, MDA and GSH contents of rats.

	Control	Pro	Dox	Dox + Pro
CK-MB (U/L)	633.00 ± 58.95	634.69 ± 55.88	1519.2 ± 76.74^$	708.96 ± 63.16*
LDH (U/L)	758.9 ± 65.39	546.41 ± 45.35	1262.8 ± 111.71^$	613.87 ± 55.49*
Catalase (K unit/g protein)	145.50 ± 12.99	156.23 ± 10.04	33.20 ± 2.94^$	47.03 ± 4.83^$
SOD (U/g tissue)	30.95 ± 0.92	27.18 ± 1.09	20.71 ± 1.41^$	26.58 ± 1.29*
MDA (nmol/g tissue)	7.92 ± 0.23	9.90 ± 0.27	12.65 ± 0.58^$	10.60 ± 0.51^$*
GSH (mg/g tissue)	35.87 ± 2.52	38.25 ± 3.14	52.47 ± 3.72^$	38.5 ± 2.91*

Data are expressed as mean ± SEM, n = 6.

Pro (70 mg/kg, orally) was given orally once daily for 9 consecutive days.

Dox (15 mg/kg, i.p.) was injected on the 7th day 1 h after Pro administration.

Biochemical measurements were determined 48 h after Dox injection.

Mean values were compared together using one-way ANOVA followed by Tukey–Kramer multiple comparisons test.

^$Significantly different from the mean value of the control group (p < 0.05).

*Significantly different from the mean value of Dox-treated group (p < 0.05).