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Rapid restoration of perfusion in ischemic myocardium is the most direct and effective treatment for coronary heart disease but may cause myocardial ischemia/reperfusion injury (MIRI). Cinnamaldehyde (CA, C9H8O), a key component in the well-known Chinese medicine cinnamomum cassia, has cardioprotective effects against MIRI. This study aimed to observe the therapeutic effect of CA on MIRI and to elucidate its potential mechanism. H9C2 rat cardiomyocytes were pretreated with CA solution at 0, 10, and 100 μM, respectively and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Then the cell viability, the NF-κB and caspase3 gene levels, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD) level, reactive oxygen species (ROS) generation, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were detected. The severity of DNA damage was assessed by tail moment (TM) values using alkaline comet assay. Besides, the DNA damage-related proteins and the key proteins of the Nrf2 pathway were detected by western blot. CA treatment increased the cell viability, GHS/GSSG ratio, SOD level, PARP1, Nrf2, PPAR-γ, and HO-1 protein levels of H9C2 cardiomyocytes, while reducing NF-κB, caspase3, ROS level, 4-HNE and MDA content, γ-H2AX protein level, and TM values. Inhibition of the Nrf2 pathway reversed the effect of CA on cell viability and apoptosis of OGD/R induced H9C2 cardiomyocytes. Besides, 100 μM CA was more effective than 10 μM CA. In the OGD/R-induced H9C2 cardiomyocyte model, CA can protect cardiomyocytes from MIRI by attenuating lipid peroxidation and repairing DNA damage. The mechanism may be related to the activation of the Nrf2 pathway., (© 2024 John Wiley & Sons Ltd.)

The aim of the present study was to establish a progressive steatohepatitis mouse model because few reported animal models of non-alcoholic steatohepatitis (NASH) show the progression from fatty liver to steatohepatitis. C57BL/6N mice were fed a high-fat diet (HFD) to develop obesity and were either administered carbon tetrachloride (CCl4 ) eight times (0.05 mL/kg, s.c., once, followed by 0.1 mL/kg, s.c., seven times) or not. Serum parameters and hepatic histopathology were examined. In a separate experiment, CCl4 was administered subcutaneously from 0 to eight times to HFD-fed obese mice to investigate progressive changes. Markers of oxidative stress, inflammation and apoptosis, as well as histopathological changes in the liver, were analysed. The HFD-fed obese mice showed fatty liver but not steatohepatitis. In contrast, HFD-fed mice administered CCl4 eight times showed histopathological features of steatohepatitis (fatty liver, inflammation, hepatocellular ballooning and fibrosis) and increased serum alanine aminotransferase levels. However, the multiple administration of CCl4 to obese mice reduced the ratio of reduced glutathione to oxidized glutathione, superoxide dismutase activity and mitochondrial DNA copy number, leading to the development of chronic oxidative stress, increased numbers of apoptotic cells and increased levels of both tumour necrosis factor-α and transforming growth factor-β mRNA. The resulting inflammation led to increased hydroxyproline content in the liver and fibrosis. The present study demonstrates that multiple administration of CCl4 to HFD-fed obese mice induces chronic oxidative stress that triggers inflammation and apoptosis and leads to the development of fibrosis in the liver, resulting in progression from fatty liver to steatohepatitis. This murine model will be useful in the research of hepatic disorders., (© 2013 Wiley Publishing Asia Pty Ltd.)