Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity

Figures & data

Table 1. Weights and CsA levels of the groups.

Groups	Initial weight (g)	Final weight (g)	CsA level (ng/mL)
Control (n = 6)	232.66 ± 3.14	233.50 ± 7.44	0
GSPE (n = 6)	229.00 ± 5.54	229.16 ± 8.03	0
CsA (n = 6)	223.00 ± 10.93	227.66 ± 8.73	1777.16 ± 783.56
CsA + GSPE (n = 6)	229.00 ± 7.32	227.50 ± 9.35	1712.43 ± 607.34

Note: CsA, cyclosporine A; GSPE, grape seed proanthocyanidin extract.

Table 2. Enzyme activities of heart tissues in the control, GSPE, CsA, and CsA + GSPE groups.

Groups	TOS (μmol H2O2 Equiv./g wet tissue)	TAS (μmol Trolox Equiv./g wet tissue)	OSI	MDA (nmol/g wet tissue)
Control (n = 6)	0.32 ± 0.05	41.56 ± 8.30	0.84 ± 0.33	103.19 ± 4.41
GSPE (n = 6)	0.40 ± 0.18	54.12 ± 7.53	0.78 ± 0.39	95.97 ± 13.56
CsA (n = 6)	0.59 ± 0.07	26.34 ± 14.17	2.75 ± 1.10	132.66 ± 17.26
CsA + GSPE (n = 6)	0.52 ± 0.07	44.54 ± 5.00	1.19 ± 0.13	103.46 ± 13.25
p-Values
Control versus GSPE	NS	0.024	NS	NS
Control versus CsA	0.004	NS	0.006	0.010
Control versus CsA + GSPE	0.004	NS	NS	NS
GSPE versus CsA	NS	0.015	0.004	0.006
GSPE versus CsA + GSPE	NS	0.035	NS	NS
CsA versus CsA + GSPE	NS	0.041	0.008	0.016

Notes: CsA, cyclosporine A; GSPE, grape seed proanthocyanidin extract; TOS, total oxidant system; TAS, total antioxidant system; OSI, oxidative stress index; MDA, malondialdehyde; NS, nonsignificant (mean ± SD). The OSI values were calculated using the following formula: [(TOS, μmol H₂O₂ Equiv./g wet tissue)/(TAS, μmol Trolox Equiv./g wet tissue)] × 100. The values are expressed as mean ± SD.

Figure 1. (A) Hematoxylin and eosin-stained sections (×400) of normal heart tissue (control). (B) Heart tissue of GSPE (100 mg/kg p.o.)-treated rats showing almost normal morphology. (C) Heart tissue of CsA-treated rats showing widespread myocardial edema, inflammation, disorganization, and mild fibrosis. (D) Heart tissue of GSPE (100 mg/kg p.o.) + CsA-treated rats showing prevention of CsA-induced alterations.

Table 3. Distribution of cardiac histopathological findings in the groups.

Groups	Inflammation	Myocardial disorganization	Interstitial fibrosis
Control	(−)	(−)	(−)
GSPE	(−)	(−)	(−)
CsA	(–/++)	(++)	(+/–)
CsA + GSPE	(+/–)	(+/–)	(−)

Note: CsA, cyclosporine A; GSPE, grape seed proanthocyanidin extract.

Figure 2. The effect of GSPE on histopathological score of myocardial cell in CsA-treated rats. The histopathological score of myocardial cell significantly increased in the CsA group compared with the control group. The histopathological score of myocardial cell significantly decreased in the CsA + GSPE group compared with the CsA group. The values are expressed as mean ± SD.

Notes: CsA, cyclosporine A; GSPE, grape seed proanthocyanidin extract. (a) CsA versus control, p = 0.007; (b) CsA + GSPE versus CsA, p = 0.041.

Figure 3. The effect of GSPE on apoptotic index of myocardial cell in CsA-treated rats. The apoptotic index is the lowest in GSPE group and the highest in CsA group. GSPE protects the heart against chronic CsA cardiotoxicity. The values are expressed as mean ± SD.

Notes: CsA, cyclosporine A; GSPE, grape seed proanthocyanidin extract. (a) GSPE versus control, p = 0.049; (b) GSPE versus CsA, p = 0.004; (c) CsA versus control, p = 0.041; (d) CsA versus CsA + GSPE, p = 0.027.

Figure 4. The effect of GSPE on apoptosis: (A) the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling)-positive myocardial cells in the control group; (B) decreased number of TUNEL-positive myocardial cells in the GSPE group; (C) increased number of TUNEL-positive myocardial cells in the CsA group; and (D) decreased number of TUNEL-positive myocardial cells in the GSPE + CsA group (TUNEL ×400).