Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo

Abstract

We previously reported that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting the MAPK pathway. The aim of this study was to test the hypothesis that NRG prevents cardiomyocytes from hyperglycemia-induced insult through the inhibition of the nuclear factor kappa B (NF-κB) pathway and the upregulation of ATP-sensitive K + (K ATP ) channels. Our results showed that exposure of cardiomyocytes to HG for 24 h markedly induced injuries, as evidenced by a decrease in cell viability and oxidative stress, and increases in apoptotic cells as well as the dissipation of mitochondrial membrane potential (MMP). These injuries were markedly attenuated by the pretreatment of cells with either NRG or pyrrolidine dithiocarbamate (PDTC) before exposure to HG. Furthermore, in streptozotocin (STZ)-induced diabetic rats and in HG-induced cardiomyocytes, the expression levels of caspase-3, bax and phosphorylated (p)-NF-κB p65 were increased. The increased protein levels were ameliorated by pretreatment with both NRG and PDTC. However, the expression levels of bcl-2 and K ATP and superoxide dismutase (SOD) activity were decreased by hyperglycemia; the expression level of Nox4 and the ADP/ATP ratio were increased by hyperglycemia. These hyperglycemia-induced indexes were inhibited by the pretreatment of cardiomyocytes with NRG or PDTC. In addition, in STZ-induced diabetic rats, we also observed that NRG or PDTC contributed to protecting mitochondrial injury and myocardium damage. This study demonstrated that NRG protects cardiomyocytes against hyperglycemia-induced injury by upregulating K ATP channels in vitro and inhibiting the NF-κB pathway in vivo and in vitro.

Angiotensin‐(1–7) protects cardiomyocytes against high glucose‐induced injuries through inhibiting reactive oxygen species‐activated leptin–p38 mitogen‐activated protein kinase/extracellular signal‐regulated protein kinase 1/2 pathways, but not the leptin–c‐Jun N‐terminal kinase pathway in vitro

“…As our previous studies reported, we showed that HG could have various degenerative effects, including cytotoxicity, apoptosis, oxidative stress and mitochondrial insult, as evidenced by the decreased cell viability, the increased apoptotic rate, the accumulation ROS generation and the loss of MMP. The ROS level is not only an oxidative stress indicator, but also one of the elements reflecting HG‐stimulated cardiomyocyte damage.…”

Trolox prevents high glucose‐induced apoptosis in rat myocardial H9c2 cells by regulating GLUT‐4 and antioxidant defense mechanism

“…Moreover, a lipid peroxidation product is known to cause DNA damage within the cell . In the present study, DNA condensation and nucleus fragmentation were significantly evident, which is consistent with earlier findings . High glucose‐induced damage was decreased in cells pretreated with Trolox (Figure ), further confirming the antioxidant nature of Trolox in protecting H9c2 cells against hyperglycemia‐induced injury.…”

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

“…Bcl-2, Bax, and Caspase-3 play critical roles in apoptosis. 56 Interestingly, Bcl-2 and Bax are generally detected at the same time in the progression of apoptosis, and the ratio of Bcl-2/Bax reflects the degree of apoptosis. Bax and Caspase-3 are pro-apoptotic proteins and Bcl-2 plays an anti-apoptotic role.…”

“…7 The ethylene oxide-propylene oxide (EO-PO) triblock copolymers have been extensively investigated. P105 is a PEO 37 -PPO 56 -PEO 37 triblock copolymer with a molecular weight of 6,500 Da and the potent ability to sensitize multidrug-resistant tumors and the capacity to encapsulate hydrophobic drugs. 8,9 OA-loaded P105/TPGS mixed micelles (OA-micelles) were prepared using a thin-film hydration method and possessed the aforementioned advantages.…”