Experimental biology and medicine
-
Exp. Biol. Med. (Maywood) · Apr 2013
[D-Ala2,D-Leu5]-enkephalin (DADLE) and morphine-induced postconditioning by inhibition of mitochondrial permeability transition pore, in human myocardium.
The aim of the study was to examine the cardioprotective effect of morphine and Delta 2 opioid D-Ala2-Leu5 enkephalin(DADLE) administered, at early reoxygenation, in isolated human myocardium exposed to hypoxia–reoxygenation. Then,we tested the involvement of mitochondrial permeability transition pore in morphine and DADLE-induced postconditioning. Human right atrial trabeculae were obtained during cardiac surgery (coronary artery bypass and aortic valve replacement). ⋯ DADLE 10 nmol did not modify the FoC60 (50+9% of baseline; P ¼ 0.60 versus control group). The enhanced recovery of FoC60 induced by morphine and DADLE 100 nmol were abolished in the presence of atractyloside (FoC60: respectively 57+6% and 44+7% of baseline;P, 0.001). In conclusion, the administration of morphine and DADLE, in early reoxygenation period, protected human myocardium, in vitro, against hypoxia–reoxygenation injury, at least in part, by the inhibition of mitochondrial permeability transition pore opening.
-
Exp. Biol. Med. (Maywood) · Feb 2013
Mesenchymal stem cells protects hyperoxia-induced lung injury in newborn rats via inhibiting receptor for advanced glycation end-products/nuclear factor κB signaling.
Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown recently to ameliorate hyperoxia-induced lung injury, but the underlying mechanism remains unclear. This study aimed to determine whether BMSCs attenuate hyperoxia-induced lung injury by down-modulating the inflammatory RAGE/NF-κB (receptor for advanced glycation end-products/nuclear factor-κB) signaling. Thirty Sprague-Dawley newborn rats were randomly divided into three groups (n = 10): sham control (C); hyperoxia-induced acute lung injury (ALI) (B) and ALI with BMSCs transplantation (A). ⋯ Moreover, RAGE and NF-κB expression in lung tissue at mRNA and protein concentrations was significantly lower in Group A than in Group B. The lung damage score was significantly lower in Group A than in Group B. These data demonstrate that hyperoxia induces the inflammation and causes damage in the lung but BMSC transplantation could alleviate hyperoxia-induced lung injury by inhibiting the inflammatory process mediated by RAGE/NF-κB signaling.
-
Exp. Biol. Med. (Maywood) · Dec 2012
Cross-talk between inflammation and angiotensin II: studies based on direct transfection of cardiomyocytes with AT1R and AT2R cDNA.
Ischemic myocardium exhibits inflammation, local angiotensin II (Ang II) generation and up-regulation of LOX-1, a lectin-like ox-LDL receptor. To define the inter-active roles of Ang II and inflammation in furthering tissue injury, cultured HL-1 cardiomyocytes were treated with Ang II. Ang II treatment up-regulated the expression of Ang II type 1 (AT1R) and type 2 (AT2R) receptors as well as LOX-1. ⋯ Forced over-expression of AT1R resulted in activation of MAPKs, c-Jun and NF-κB, up-regulation of inflammatory genes and LOX-1; on the other hand forced AT2R over-expression induced up-regulation of pro-apoptotic signals (pro-IL-1β and IL-1β), and decreased LOX-1 expression. These studies show that both Ang II and inflammation mediator LPS up-regulate AT1R, AT2R and LOX-1 expression. Up-regulation of AT1R promotes inflammation and LOX-1 expression, whereas up-regulation of AT2R promotes apoptosis signals and decreases LOX-1 expression.
-
Exp. Biol. Med. (Maywood) · Nov 2012
Laser-treated Nucleus pulposus as an innovative model of intervertebral disc degeneration.
This study describes an innovative experimentally induced model of intervertebral disc degeneration. This innovative approach is based on the induction of extracellular matrix disorders in the intervertebral disc (IVD) using a diode laser. For this study, 15 one-year-old and five 30-month-old New Zealand White rabbits were used. ⋯ The radiological, MRI and histological data confirm its relevance. The histological examination indicates that IVD degeneration induced by laser treatment is comparable to the degenerative process observed during the onset of spontaneous IVD degeneration. This model could be a useful tool to help us validate biomaterial-assisted, cell-based, regenerative medicine strategies for the prevention and treatment of IVD degeneration.
-
Exp. Biol. Med. (Maywood) · Jun 2012
Ethyl pyruvate reduces ventilation-induced neutrophil infiltration and oxidative stress.
Mechanical ventilation with high tidal volume causes intense inflammatory responses and oxidative stress, including the release of high-mobility group box-1 (HMGB1), plasminogen activator inhibitor-1 (PAI-1) and heme oxygenase-1 (HO-1). The mechanisms regulating ventilator-induced lung injury (VILI) are unclear. We hypothesized that ethyl pyruvate attenuated acute lung injury as adjunctive pharmacological strategy by down-regulating neutrophil infiltration, oxidative stress and HMGB1 mRNA expression. ⋯ In contrast, administration of ethyl pyruvate before high stretch mechanical ventilation prevented lung edema formation, inflammatory cytokine production, neutrophil accumulation, oxidative stress and HMGB1 and HO-1 expression. High-tidal-volume mechanical ventilation increased microvascular permeability, neutrophil influx and inflammatory cytokines. Ethyl pyruvate is capable of suppressing the VILI related to the reduction of HMGB1 and our findings support the potential use of ethyl pyruvate as a therapeutic agent for the prevention of VILI.