Evaluation of Ameliorative Effect of Quercetin and Candesartan in Doxorubicin-Induced Cardiotoxicity

Figures & data

Table 1 Route, Dose and Description of Drug Administration

Group	Description	Route and Dose of Drug	Description of Drug Administration
Group 1 (Control)	Normal group	Same volume of solvent	–
Group 2 (DOX)	DOX-treated group	DOX (2.5 mg/kg, i. p.)	06 equivalent injections at 48 hours interval for 02 consecutive weeks to achieve a cumulative dose of 15 mg/kg
Group 3 (DQ)	DOX + QRN treated group	QRN suspension (10 mg/kg/day; orally) to rats	QRN administration was started along with DOX and further continued for 4 weeks (6 weeks total period).
Group 4 (DC)	DOX + CAN treated group	CAN (5 mg/kg/day; Orally)	CAN was started along with DOX and continued for further for 4 weeks (6-weeks period)
Group 5 (DQC)	DOX+QRN+CAN treated group	Combined administration of QRN + CAN started along with DOX and further continued for 4 weeks (6 weeks total period)

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 2 Effect of CAN, QRN and CAND+ QRN on Heart/Body Weight Ratio

Treatment	Body Weight (g)	Heart Weight (g)	Heart/Body Weight Ratio (x10^−3)
Control	240 ± 3.81	0.515 ± 0.07	2.145 ± 0.12
DOX	190 ± 6.72	0.670 ± 0.01	3.526 ± 0.22^#
DOX + CAN	195 ± 4.06	0.615 ± 0.03	3.153 ± 0.18
DOX + QRN	215 ± 5.46	0.595 ± 0.03	2.767 ± 0.15*
DOX + QRN + CAN	235 ± 6.33	0.535 ± 0.06	2.276 ± 0.12*

Notes: Data were expressed as mean ± S.E.M. (n=8). ^#(p<0.05) when NC vs DOX. *(p<0.05) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 3 Effect of CAN, QRN and CAND+ QRN on Plasma Markers of Cardiac Damage

Treatment	CK-MB (IU/L)	LDH (IU/L)
Control	131.2±10.09	182.4±16.99
DOX	352.4±16.99^###	661.7±20.45^###
DOX + CAN	251.8±14.92**	311.3±28.35**
DOX + QRN	216.7±14.24**	296.1±8.90***
DOX + QRN + CAN	164.7±7.605***	251.3±20.49***

Notes: Data were expressed as mean ± S.E.M (n=8). ^###(p<0.001) when NC vs DOX. ** (p<0.01), ***(p<0.001) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+ CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 4 Effect of CAN, QRN and CAND+ QRN on Antioxidant Level

Treatment	CAT (nmol/mg Protein)	GSH (nmol/mg Protein)	SOD (U/mg Protein)
Control	4.08±0.12	28.29±0.43	5.51±0.088
DOX	1.43±0.12^###	8.48±0.42^###	2.09±0.031^###
DOX + CAN	2.55±0.14**	19.4±1.01***	4.02±0.044**
DOX + QRN	2.84±0.16***	20.75±1.02***	2.97±0.008***
DOX + QRN + CAN	3.54±0.32***	23.12±0.64***	3.23±0.015***

Notes: Data were expressed as mean ± S.E.M. (n=8). ^###(p<0.001) when NC vs DOX. **(p<0.01), ***(p<0.001) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 5 Effect of CAN, QRN and CAN+ QRN on Cardiac LPO Levels and NO Level

Treatment	LPO (µmol/mg Protein)	Total Nitrate (nmol/mg Protein)
Control	19.17±1.20	5.62±0.61
DOX	33.12±1.63^###	13.33±0.73^###
DOX + CAN	16.90±0.90**	9.47±0.30***
DOX + QRN	16.69±0.89***	8.93±0.31***
DOX + QRN + CAN	18.59±0.65***	5.80±0.39***

Notes: Data were expressed as mean ± S.E.M (n=8). ^###(p<0.001) when NC vs DOX. **(p<0.01), ***(p<0.001) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 6 Effect of CAN, QRN and CAN+QRN on Plasma Lipid Profile

Treatment	TC (mg/dL)	TG (mg/dL)	VLDL (mg/dL)
Control	57.67±3.83	81.18±5.31	16.24±1.06
DOX	118.4±4.25^###	263.3±9.99^###	52.66±1.99^###
DOX+CAN	64.98±2.59***	113.7±4.86***	22.74±0.97**
DOX + QRN	77.91±4.11***	97.63±7.77***	19.53±1.55***
DOX+QRN+ CAN	81.83±3.59***	109.2±8.97***	21.84±1.79***

Notes: Data were expressed as mean ± S.E.M (n=8). ^###(p<0.001) when NC vs DOX. **(p<0.01), ***(p<0.001) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Table 7 Effect of CAN, QRN and CAN+QRN on Plasma Lipid Profile and Serum Troponin-T Levels

Treatment	LDL (mg/dL)	HDL (mg/dL)	Troponin T (pg/mL)
Control	19.73±2.78	21.70±0.65	0.29 ± 0.01
DOX	52.99±5.80^###	12.78±0.36^###	1.82 ± 0.11^###
DOX+CAN	24.47±2.62***	18.78±1.58**	0.39 ± 0.03**
DOX + QRN	25.69±3.96***	17.69±2.26**	0.42 ± 0.01**
DOX+QRN+ CAN	21.29±3.96***	19.08±2.20**	0.34 ± 0.02**

Notes: Data were expressed as mean ± S.E.M (n=8). ^###(p<0.001) when NC vs DOX. **(p<0.01), ***(p<0.001) when DOX vs DOX+CAN, DOX vs DOX+QRN and DOX vs DOX+QRN+CAN.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Figure 1 Effect of CAN, QRN, and CAN+ QRN on morphometry of cardiac tissue. Yellow arrows depict brick red coloration indicative of a greater number of viable cells in treatment groups.

Abbreviations: DOX, doxorubicin; QRN, quercetin; CAN, candesartan.

Figure 2 Effect of CAN, QRN, and CAN+ QRN on histopathology of cardiac tissue. (DOX – doxorubicin; QRN – quercetin; CAN – candesartan) Blue arrow depicts more amount of leukocyte infiltration and intramuscular hemorrhage in DOX treated group as compared to the treatment groups.