Effects of Curcumin Nanoparticles in Isoproterenol-Induced Myocardial Infarction

Abstract

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.

Figure 1

Distribution of serum levels of myocardial infarction enzymes ((a) CK (creatine kinase) and (b) CK-MB (creatine kinase-MB)) by groups. The horizontal line is given by the median, and the circles represent the individual values. C = control; ISOC = isoproterenol without any pretreatment; CC = curcumin solution, in doses of 100 mg/kg bw (CC100), 150 mg/kg bw (CC150), and 200 mg/kg bw (CC200); CCNP = curcumin nanoparticle solution, in doses of 100 mg/kg bw (CCNP100), 150 mg/kg bw (CCNP150), and 200 mg/kg bw (CCNP200). The Roman and Greek letters correspond to the p values < 0.03: ^aISOC compared to C, ^bCC100+ISO compared to ISOC, ^cCC150+ISO compared to ISOC, ^dCC200+ISO compared to ISOC, ^eCCNP100+ISO compared to ISOC, ^fCCNP150+ISO compared to ISOC, ^gCCNP200+ISO compared to ISOC, ^ACC100+ISO compared to CC150+ISO, ^BCC150+ISO compared to CC200+ISO, ^CCC100+ISO compared to CC200+ISO, ^XCCNP100+ISO compared to CCNP150+ISO, ^YCCNP150+ISO compared to CCNP200+ISO, ^ZCCNP100+ISO compared to CCNP200+ISO, ^αCC100+ISO compared to CCNP100+ISO, ^βCC150+ISO compared to CCNP150+ISO, and ^μCC200+ISO compared to CCNP200+ISO.

Figure 2

Distribution of oxidative stress intensity ((a) NOx (nitric oxide), (b) MDA (malondialdehyde), and (c) TOS (total oxidative status)) by groups. The horizontal line is given by the median, and the circles represent the individual values. C = control; ISOC = isoproterenol without any pretreatment; CC = curcumin solution, in doses of 100 mg/kg bw (CC100), 150 mg/kg bw (CC150), and 200 mg/kg bw (CC200); CCNP = curcumin nanoparticle solution, in doses of 100 mg/kg bw (CCNP100), 150 mg/kg bw (CCNP150), and 200 mg/kg bw (CCNP200). The Roman and Greek letters correspond to the p values < 0.05: ^aISOC compared to C, ^bCC100+ISO compared to ISOC, ^cCC150+ISO compared to ISOC, ^dCC200+ISO compared to ISOC, ^eCCNP100+ISO compared to ISOC, ^fCCNP150+ISO compared to ISOC, ^gCCNP200+ISO compared to ISOC, ^ACC100+ISO compared to CC150+ISO, ^BCC150+ISO compared to CC200+ISO, ^CCC100+ISO compared to CC200+ISO, ^XCCNP100+ISO compared to CCNP150+ISO, ^ZCCNP100+ISO compared to CCNP200+ISO, ^αCC100+ISO compared to CCNP100+ISO, ^βCC150+ISO compared to CCNP150+ISO, and ^μCC200+ISO compared to CCNP200+ISO.

Figure 3

Distribution of antioxidant capacity ((a) thiol and (b) TAC (total antioxidant capacity)) by groups. C = control; ISOC = isoproterenol without any pretreatment; CC = curcumin solution, in doses of 100 mg/kg bw (CC100), 150 mg/kg bw (CC150), and 200 mg/kg bw (CC200); CCNP = curcumin nanoparticle solution, in doses of 100 mg/kg bw (CCNP100), 150 mg/kg bw (CCNP150), and 200 mg/kg bw (CCNP200). The Roman and Greek letters correspond to the p values < 0.05: ^aISOC compared to C, ^bCC100+ISO compared to ISOC, ^cCC150+ISO compared to ISOC, ^dCC200+ISO compared to ISOC, ^eCCNP100+ISO compared to ISOC, ^fCCNP150+ISO compared to ISOC, ^gCCNP200+ISO compared to ISOC, ^ACC100+ISO compared to CC150+ISO, ^BCC150+ISO compared to CC200+ISO, ^CCC100+ISO compared to CC200+ISO, ^YCCNP150+ISO compared to CCNP200+ISO, ^ZCCNP100+ISO compared to CCNP200+ISO, ^αCC100+ISO compared to CCNP100+ISO, ^βCC150+ISO compared to CCNP150+ISO, and ^μCC200+ISO compared to CCNP200+ISO.

Figure 4

Distribution of serum cytokine levels ((a) TNF-α (tumor necrosis factor alpha), (b) IL-6 (interleukin 6), (c) IL-1α (interleukin 1a), (d) IL-1β (interleukin 1β), (e) MCP1 (monocyte chemoattractant protein-1), and (f) RANTES (regulated upon activation, normal T cell expressed and secreted)) by groups. C = control; ISOC = isoproterenol without any pretreatment; CC = curcumin solution, in doses of 100 mg/kg bw (CC100), 150 mg/kg bw (CC150), and 200 mg/kg bw (CC200); CCNP = curcumin nanoparticle solution, in doses of 100 mg/kg bw (CCNP100), 150 mg/kg bw (CCNP150), and 200 mg/kg bw (CCNP200). The Roman and Greek letters correspond to the p values < 0.05: ^aISOC compared to C, ^bCC100+ISO compared to ISOC, ^cCC150+ISO compared to ISOC, ^dCC200+ISO compared to ISOC, ^eCCNP100+ISO compared to ISOC, ^fCCNP150+ISO compared to ISOC, ^gCCNP200+ISO compared to ISOC, ^ACC100+ISO compared to CC150+ISO, ^BCC150+ISO compared to CC200+ISO, ^CCC100+ISO compared to CC200+ISO, ^XCCNP100+ISO compared to CCNP150+ISO, ^YCCNP150+ISO compared to CCNP200+ISO, ^ZCCNP100+ISO compared to CCNP200+ISO, ^αCC100+ISO compared to CCNP100+ISO, ^βCC150+ISO compared to CCNP150+ISO, and ^μCC200+ISO compared to CCNP200+ISO.

Figure 5

Distribution of serum matrix metalloproteinases ((a) MMP-2 (matrix metalloproteinase-2) and (b) MMP-9 (matrix metalloproteinase-9)) per group. C = control; ISOC = isoproterenol without any pretreatment; CC = curcumin solution, in doses of 100 mg/kg bw (CC100), 150 mg/kg bw (CC150), and 200 mg/kg bw (CC200); CCNP = curcumin nanoparticle solution, in doses of 100 mg/kg bw (CCNP100), 150 mg/kg bw (CCNP150), and 200 mg/kg bw (CCNP200). The Roman and Greek letters correspond to the p values < 0.05: ^aISOC compared to C, ^bCC100+ISO compared to ISOC, ^cCC150+ISO compared to ISOC, ^dCC200+ISO compared to ISOC, ^eCCNP100+ISO compared to ISOC, ^fCCNP150+ISO compared to ISOC, ^gCCNP200+ISO compared to ISOC, ^ACC100+ISO compared to CC150+ISO, ^CCC100+ISO compared to CC200+ISO, ^XCCNP100+ISO compared to CCNP150+ISO, ^ZCCNP100+ISO compared to CCNP200+ISO, ^αCC100+ISO compared to CCNP100+ISO, ^βCC150+ISO compared to CCNP150+ISO, and ^μCC200+ISO compared to CCNP200+ISO.

Figure 6

Histopathology on the basis of severity of changes: (a) grade 1—normal myocardial tissue, (b) grade 2—focal myocardial fiber necrosis (orange arrow), (c) grade 3—focal myocardial fiber necrosis (orange arrow) with associated inflammation (yellow arrow), and (d) grade 4—extensive or multifocal myocardial fiber necrosis (orange arrow) with extensive associated inflammation (red arrow).