## 4 Discussion
### Serum Levels of Matrix Metalloproteinases  
Conventional curcumin and NC prevented the increase in MMP-2 and MMP-9. The best results were obtained for NC compared to CC, especially in rats who received the nanoparticles before T1 DM induction (Figure 9).  
Matrix metalloproteinases (MMPs) are a family of zinc-binding proteolytic enzymes that pathologically attack substrates as part of an inflammatory response and have an important role in the extracellular matrix (ECM) reorganization [46]. MMP-2, or gelatinase A, is found in nearly all cell types and is involved in the degradation of denatured collagen and collagen type IV, a significant component of the basement membrane [47]. It may also be responsible for proteolysis of cytoskeletal proteins, increasing oxidative stress, so its inhibition can attenuate tissue damage [48]. MMP-9 is implicated in the regulation of tissue remodeling since it directly degrades extracellular matrix proteins and activates cytokines and chemokines involved in this process [49]. Apart from inflammation and oxidative stress, matrix MMPs can play an essential role in diabetes mellitus pathogenesis and contribute to vascular complications, especially in diabetic retinopathy due to the capillary cell apoptosis mechanism [50]. MMP-2 serum levels were reported to rise early in diabetes mellitus within the first 5 years from the onset of diagnosis and to be markedly raised with the disease's progression [51]. Elevated expression and enhanced activity of MMP-9 in diabetes mellitus is due to acute stimuli, such as vascular injury or as inflammatory mediators [52]. Systemic concentrations of MMP-2 and MMP-9, in addition to gelatinase activity levels, are also increased in patients with T2 DM and peripheral arterial disease [53]. MMP-2 and MMP-9 are activated in the myocardial tissue after AMI's onset; therefore, they were studied for their roles in left ventricular remodeling and post-myocardial infarction prognosis [54]. Inhibition of MMP-2 was associated with a higher survival rate and with less left ventricular adverse remodeling after AMI in mice [54], while MMP-9 inhibition was associated with a lower incidence of myocardial wall rupture after AMI and reduced left ventricular dilation, explained by the reduced collagen reorganization in the infarcted area [55]. Curcumin treatment inhibits both MMP-2 and MMP-9 through its potent antioxidant and anti-inflammatory effect [56]. Curcumin nanoparticles were already proven effective in reducing MMP-2 and MMP-9 in streptozotocin-induced T1 DM [57]. Our study is the first to report the effect of curcumin and curcumin nanoparticle pretreatment on MMP-2 and MMP-9 expression in AMI in rats with T1 DM. Due to their ability to reduce the activity of active matrix metalloproteinases, curcumin and curcumin nanoparticles can be used as an adjuvant treatment for reducing the vascular complication of diabetes mellitus [57] and to improve systolic function and promotion of the cardiac remodeling process [56] after AMI in patients with diabetes mellitus. Curcumin nanoparticles exert greater effects on MMPs activity than curcumin due to their increased solubility and higher resistance to enzymatic degradation [57].