Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes

Abstract

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

Keywords: curcumin; isoproterenol; myocardial infarction; nanoparticles; oxidative stress.

Figure 1

ECG record on day 0, at the beginning of the experiment.

Figure 2

ECGs on day 12 (before ISO administration). Increased RR interval (black arrow). (a) C = Control; (b) MI-C = MI without any pre-treatment; (c) curcumin solution, as 100 mg/kg bw (Cs100), (d) curcumin solution, as 150 mg/kg bw (Cs150), (e) curcumin solution, as 200 mg/kg bw (Cs200); (f) curcumin nano-particle solution as 100 mg/kg bw (nC100), (g) curcumin nano-particle solution as 150 mg/kg bw (nC150), and (h) curcumin nano-particle solution as 200 mg/kg bw (nC200); ISO = isoproterenol.

Figure 3

ECGs on day 15 (after ISO administration). Increased RR interval (black arrow), enlargement of the QRS complex (orange arrow), increased QT interval (red arrow), ST-segment depression (green arrow), T wave inversion (yellow arrow). (a) C = Control; (b) MI-C = myocardial infarction (MI) without any pre-treatment; (c) curcumin solution, as 100 mg/kg bw (Cs100), (d) curcumin solution, as 150 mg/kg bw (Cs150), (e) curcumin solution, as 200 mg/kg bw (Cs200); (f) curcumin nano-particle solution as 100 mg/kg bw (nC100), (g) curcumin nano-particle solution as 150 mg/kg bw (nC150), and (h) curcumin nano-particle solution as 200 mg/kg bw (nC200); ISO = isoproterenol.

Figure 4

Serum levels of lactate dehydrogenase (LDH) by groups. C = control; MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). The letter-number codes correspond to the p-values < 0.05: ^α as compared with MI-C, ^β as compared with CS100+ISO, ^γ as compared with CS150+ISO, ^λ as compared with nC100+ISO, ^μ as compared with nC150+ISO, ^ε as compared with Cs200+ISO.

Figure 5

Serum levels of: (a) aspartate transaminase (AST) and (b) alanine transaminase (ALT) by groups. C = control; MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). The letter-number codes correspond to the p-values < 0.05: ^α as compared with MI-C, ^β as compared with CS100+ISO, ^γ as compared with CS150+ISO, ^λ as compared with nC100+ISO, ^μ as compared with nC150+ISO, ^ε as compared with Cs200+ISO.

Figure 6

Serum levels of glycemia by groups. C = control; MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). The letter-number codes correspond to the p-values < 0.05: ^α as compared with MI-C, ^β as compared with CS100+ISO, ^γ as compared with CS150+ISO, ^λ as compared with nC100+ISO, ^ε as compared with Cs200+ISO.

Figure 7

Distribution of oxidative stress intensity in the myocardial tissue: (a) nitric oxide (NOx), (b) malondialdehyde (MDA), and (c) total oxidative status (TOS) by groups. C = control; MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200); the letter-number codes correspond to the p-values < 0.05: ^α as compared with MI-C, ^β as compared with CS100+ISO, ^γ as compared with CS150+ISO, ^λ as compared with nC100+ISO, ^μ as compared with nC150+ISO, ^ε as compared with Cs200+ISO.

Figure 8

Distribution of antioxidant capacity in the myocardial tissue: (a) Thiol and (b) total antioxidant capacity (TAC) by groups. C = control; MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). The letter-number codes correspond to the p-values < 0.05: ^α as compared with MI-C, ^β as compared with CS100+ISO, ^γ as compared with CS150+ISO, ^λ as compared with nC100+ISO, ^μ as compared with nC150+ISO, ^ε as compared with Cs200+ISO.

Figure 9

Differences relative to the control (no myocardial infarction, C group) of serum analysis represented by lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), and glycaemia. * extreme value; ^○ outlier.

Figure 9

Differences relative to the control (no myocardial infarction, C group) of serum analysis represented by lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), and glycaemia. * extreme value; ^○ outlier.

Figure 10

Differences relative to the control (no myocardial infarction, C group) of antioxidant capacity in the myocardial tissue: Thiol and total antioxidant capacity (TAC) by groups and of oxidative stress intensity in the myocardial tissue: nitric oxide (NOx), malondialdehyde (MDA), and total oxidative status (TOS) by groups. MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). * extreme value; ^○ outlier.

Figure 10

Differences relative to the control (no myocardial infarction, C group) of antioxidant capacity in the myocardial tissue: Thiol and total antioxidant capacity (TAC) by groups and of oxidative stress intensity in the myocardial tissue: nitric oxide (NOx), malondialdehyde (MDA), and total oxidative status (TOS) by groups. MI-C = isoproterenol without any pre-treatment; Cs = curcumin solution, in doses of 100 mg/kg bw (Cs100), 150 mg/kg bw (Cs150), and 200 mg/kg bw (Cs200); nC = curcumin nanoparticle solution, in doses of 100 mg/kg bw (nC100), 150 mg/kg bw (nC150), and 200 mg/kg bw (nC200). * extreme value; ^○ outlier.

Figure 11

Flow chart demonstrating the experimental study groups.

Figure 12

Blood pressure measurement method.