Oyster broth concentrate and its major component taurine alleviate acute alcohol-induced liver damage.

Our previous study showed that oyster hydrolysate (OH) protected against the liver damage caused by a single instance of ethanol (EtOH) binge drinking. Oyster broth concentrate (OBC) was discovered in the process of searching for a different substance derived from oysters (Crassostrea gigas) with economic value. OBC is a by-product of boiling oysters at 95°C for 3 min. In this study, we investigated the effects of OBC and its major component taurine on blood and liver tissues obtained from a single-EtOH-binge-drinking mouse model. The preadministration of OBC enhanced EtOH metabolism by increasing the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and catalase. In addition, the preadministration of OBC reduced cytochrome P450 2E1 (CYP2E1) activity, reactive oxygen species (ROS) generation, Ca2+ concentrations, apoptotic signals, and inflammatory mediators in liver tissues. The reduction of apoptotic and inflammatory signals by OBC resulted from the downregulation of endoplasmic reticulum (ER) stress molecules and NF-κB activity. Taurine administration showed similar effects to OBC. These results show that OBC protected against acute EtOH-induced liver damage through the action of taurine. Our findings suggest that OBC could be an economically valuable substance and a functional food with hepatoprotective effects.

Oyster-Derived Tyr-Ala (YA) Peptide Prevents Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure by Suppressing Inflammatory, Apoptotic, Ferroptotic, and Pyroptotic Signals.

Models created by the intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) have been widely used to study the pathogenesis of human acute liver failure (ALF) and drug development. Our previous study reported that oyster (Crassostrea gigas) hydrolysate (OH) had a hepatoprotective effect in LPS/D-GalN-injected mice. This study was performed to identify the hepatoprotective effect of the tyrosine-alanine (YA) peptide, the main component of OH, in a LPS/D-GalN-injected ALF mice model. We analyzed the effect of YA on previously known mechanisms of hepatocellular injury in the model. LPS/D-GalN-injected mice showed inflammatory, apoptotic, ferroptotic, and pyroptotic liver injury. The pre-administration of YA (10 mg/kg or 50 mg/kg) significantly reduced the liver damage factors. The hepatoprotective effect of YA was higher in the 50 mg/kg YA pre-administered group than in the 10 mg/kg YA pre-administered group. These results showed that YA had a hepatoprotective effect by reducing inflammation, apoptosis, ferroptosis, and pyroptosis in the LPS/D-GalN-injected ALF mouse model. We suggest that YA can be used as a functional peptide for the prevention of acute liver injury.

Upregulation of TRESK Channels Contributes to Motor and Sensory Recovery after Spinal Cord Injury.

TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TGTRESK). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (p < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TGTRESK SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TGTRESK mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1ß concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TGTRESK SCI mice compared to WT-SCI mice (p < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.

Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models.

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

Involvement of mitochondrial biogenesis during the differentiation of human periosteum-derived mesenchymal stem cells into adipocytes, chondrocytes and osteocytes.

Due to a rapidly expanding aging population, the incidence of age-related or degenerative diseases has increased, and efforts to handle the issue with regenerative medicine via adult stem cells have become more important. And it is now clear that the mitochondrial energy metabolism is important for stem cell differentiation. When stem cells commit to differentiate, glycolytic metabolism is being shifted to mitochondrial oxidative phosphorylation (OXPHOS) to meet an increased cellular energy demand required for differentiated cells. However, the nature of cellular metabolisms during the differentiation process of periosteum-derived mesenchymal stem cells (POMSC) is still unclear. In the present study, we investigated mitochondrial biogenesis during the adipogenic, chondrogenic, and osteogenic differentiation of POMSCs. Both mitochondrial DNA (mtDNA) contents and mitochondrial proteins (VDAC and mitochondrial OXPHOS complex subunits) were increased during all of these mesenchymal lineage differentiations of POMSCs. Interestingly, glycolytic metabolism is reduced as POMSCs undergo osteogenic differentiation. Furthermore, reducing mtDNA contents by ethidium bromide treatments prevents osteogenic differentiation of POMSCs. In conclusion, these results indicate that mitochondrial biogenesis and OXPHOS metabolism play important roles in the differentiation of POMCS and suggest that pharmaceutical modulation of mitochondrial biogenesis and/or function can be a novel regulation for POMSC differentiation and regenerative medicine.

Involvement of TREK-1 Channel in Cell Viability of H9c2 Rat Cardiomyoblasts Affected by Bupivacaine and Lipid Emulsion.

Lipid emulsion (LE) therapy has been used to reduce overdose of bupivacaine (BPV)-induced cardiotoxicity. The TWIK-related potassium channel-1 (TREK-1) is inhibited by BPV and activated by polyunsaturated fatty acids, which are the main component in LE. These pharmacological properties inspired us to investigate whether the TREK-1 channel is associated with cell viability of H9c2 cardiomyoblasts affected by BPV and LE. Consistent with previous studies, BPV-induced cell death was reduced by LE treatment. The reduction in the TREK-1 expression level by BPV was alleviated by LE. The BPV cytotoxicity highly decreased in TREK-1 overexpressed cells but was the opposite in TREK-1 knocked-down cells. TREK-1 channel activators and inhibitors increased and decreased cell viability, respectively. BPV-induced depolarization of the plasma and mitochondrial membrane potential and increase in intracellular Ca2+ level were blocked by LE treatment. BPV-induced depolarization of membrane potential was reduced in TREK-1 overexpressed cells, indicating that TREK-1 channels mediate setting the resting membrane potentials as a background K+ channel in H9c2 cells. These results show that TREK-1 activity is involved in the BPV cytotoxicity and the antagonistic effect of LE in H9c2 cells and suggest that TREK-1 could be a target for action of BPV and LE.