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Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia-reperfusion (GCIR)-induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest-cardiopulmonary resuscitation (CA-CPR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal death in GCIR-injured brain post-CA-CPR. Using normal controls (Sham group) and two experimental groups [CA-CPR-induced GCIR injury (PCAS) group and exogenous treatment with adiponectin post-CA-CPR (APN group)], it was demonstrated that both apoptosis and autophagy were observed simultaneously in the brain subjected to GCIR, but apoptosis appeared to be more apparent. Exogenous administration of APN significantly reduced the formation of malondialdehyde, a marker of oxidative stress and increased the expression of superoxide dismutase, an anti-oxidative enzyme, resulting in the stimulation of autophagy, inhibition of apoptosis and reduced brain tissue injury (P<0.05 vs. PCAS). APN treatment increased the expression of APN receptor 1 (AdipR1) and the phosphorylation of AMP-activated protein kinase (AMPK; Ser182) in brain tissues. In conclusion, GCIR induced apoptosis and inhibited autophagy, contributing to brain injury in CA-CPR. By contrast, APN reduced the brain injury by reversing the changes of neuronal autophagy and apoptosis induced by GCIR. The possible mechanism might owe to its effects on the activation of AMPK after combining with AdipR1 on neurons, which suggests a novel intervention against GCIR injury in CA-CPR conditions. [ABSTRACT FROM AUTHOR]

The present study explored the protective effect of exogenous hydrogen sulfide (H2S) on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and the underlying mechanisms. To establish an AKI injury mouse model, LPS (10 mg/kg) was intraperitoneally injected into mice pretreated with 0.8 mg/kg sodium hydrosulfide hydrate (NaHS), an H2S donor. The mouse survival rate and the degree of kidney injury were examined. To construct a cell damage model, HK-2 cells were pretreated with different concentrations (0.1, 0.3 and 0.5 mM) of NaHS, and then the cells were stimulated with LPS (1 µg/ml). The cell viability, autophagy, apoptosis levels and the release of inflammatory factors were examined in mouse kidney tissue and HK-2 renal tubular epithelial cells. It was found that pretreatment with NaHS significantly improved the survival rate of septic AKI mice, and reduced the renal damage, release of inflammatory factors and apoptosis. In HK-2 cells, NaHS protected cells from LPS caused damage via promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. In order to clarify the relationship between autophagy and apoptosis and inflammatory factors, this study used 3-methyladenine (3-MA) to inhibit autophagy. The results revealed that 3-MA eliminated the protective effect of NaHS in HK-2 cells and AKI mice. Overall, NaHS can protect from LPS-induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. [ABSTRACT FROM AUTHOR]

Sepsis-induced myocardial dysfunction is one of the features of multiple organ dysfunction in sepsis, which is associated with extremely high mortality and is characterized by impaired myocardial compliance. To date, there are few effective treatment options available to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis; however, the underlying mechanisms by which TA protects against septic heart injury remain elusive. The present study investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)-induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 µg/ml), TA (10 µM) and TA + LPS; control cells were treated with medium only. Apoptosis was measured using flow cytometry, reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT-qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress-associated functional proteins. The present findings demonstrated that TA reduced the degree of LPS-induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)-associated apoptosis. ERS-associated functional proteins, including activating transcription factor 6, protein kinase-like ER kinase, inositol-requiring enzyme 1, spliced X box-binding protein 1 and C/EBP-homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS-associated apoptotic proteins, including c-Jun N-terminal kinase, Bax, cytochrome c, caspase-3, caspase-12 and caspase-9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS-induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N-acetylcysteine, which demonstrated that ROS mediated ERS-associated apoptosis and TA was able to decrease ROS-mediated ERS-associated apoptosis. Collectively, the present findings demonstrated that the protective effects of TA against LPS-induced H9C2 cell apoptosis may be associated with the amelioration of ROS-mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury. [ABSTRACT FROM AUTHOR]