Bisphenol A (BPA) is a widely distributed environmental endocrine disruptor. The accumulation of BPA has been proved that produce various toxic effects both on human and animals. However, the strategies to reduce the damage of BPA on the body and related mechanisms remain to be studied. Coenzyme Q10 (CoQ10), as a powerful antioxidant, is ubiquitous in many eukaryotic cells, which can improve the integrity of lysosomal membrane, lysosomal degradation function and promote autophagy. Here, we examined the ability of CoQ10 to alleviate oxidative stress and apoptosis in BPA-induced damages in C2C12 cells, and how to alleviate it. Our results showed that BPA treatment significantly reduced cell viability, increased the number of cell apoptosis and ROS production, decreased mitochondrial membrane potential, and inhibited the gene expression of mitochondria biogenesis. Moreover, we demonstrated that exposure to BPA increased expression levels of autophagy protein (LC3-II, p62), inhibited autophagy flux, and disrupted the acidic pH environment of lysosomes. Importantly, CoQ10 supplementation effectively restored these abnormalities caused by BPA. CoQ10 significantly decreased the apoptotic incidence and ROS levels, improved mitochondrial membrane potential. Moreover, CoQ10 improved lysosome function and enhanced autophagy flux. Taken together, our results indicate that CoQ10 supplementation is a feasible and effective way to promote the level of autophagy by improving lysosomal function, thereby reducing the apoptosis caused by BPA accumulation. This study aims to provide evidence for the role of CoQ10 in repairing BPA-induced cell damage in clinical practice.
1 January 2022 in Oxidative Medicine and Cellular Longevity
Phloretin (PHL) is a dihydrochalcone flavonoid isolated from the peel and root bark of apples, strawberries, and other plants with antioxidative characteristic. In this study, we aimed to investigate the protective effect and the potential mechanism of PHL on hydrogen peroxide (H2O2)‐induced oxidative damage in DF‐1 cells. The results showed that PHL exhibited no cytotoxic effect on DF‐1 cells at concentration below 20 μM. PHL markedly increased H2O2‐reduced cell viability, decreased H2O2‐induced apoptosis, as evidenced by reduced apoptosis rate, the upregulation of gene and protein level of Bcl‐2, and the downregulation of gene and protein level of Bax and Cleaved caspase3. In addition, PHL reduced H2O2‐induced reactive oxygen species (ROS) production and restored antioxidant enzymes activities as well as mitochondrial membrane potential in a dose‐dependent manner. Moreover, PHL prior to H2O2 further increased LC3‐II level, promoted p62 turnover and improved lysosomal function. Importantly, autophagy inhibitor chloroquine (CQ) reversed the protective effect of PHL, and increased H2O2‐induced apoptosis. Furthermore, PHL inhibited the phosphorylation levels of ERK, p38, and JNK. Collectively, these results indicate that PHL could attenuate H2O2‐induced oxidative injury and apoptosis by maintaining lysosomal function and promoting autophagic flux, and MAPKs pathway may be involved in this process. Our study provides evidence that PHL could as a new strategy to against oxidative damage in poultry industry.
The gut microbiota plays a vital role in regulating the host’s physiological functions, including metabolism and immunity. The microbial composition and metabolism are modulated by multiple factors; host sex is an important yet under-explored determinant. To investigate the sex-dependent differences in the gut microbiota within the small and large intestine, sixteen somatic mature Jiangshan black pigs (eight males and eight females) were analyzed. The ileal and colonic microbial community and metabolites were profiled using 16S rRNA gene high-throughput sequencing and gas chromatography. Distinct sex-related discrepancies were observed in both the microbial composition and metabolism of the ileum and colon. In the ileum, compared with the male group, the female group exhibited higher abundances of Unclassified Chloroplast and Pseudomonas but a lower abundance of Romboutsia (adjusted p < 0.05). Functional prediction indicated enrichment in amino acid metabolism pathway in females, with more copy numbers of genes encoding key enzymes for propionate (mmdA) generation and elevated valerate levels (p < 0.05). In the colon, compared with the male group, the female group showed higher abundances of Streptococcus, Phascolarctobacterium, and Prevotella spp. and lower abundances of Eubacterium coprostano-ligenes group, Blautia, Christensenellaceae R-7 group, and Ruminococcus (adjusted p < 0.05). Additionally, the female group had more copies of genes mmdA and LcdA (associated with lactate production), along with higher concentrations of propionate and lactate (p < 0.05). Correlation analysis between microbial metabolites and sex-biased bacteria further revealed that the SCFA concentration positively correlated with Prevotella spp. and negatively correlated with Romboutsia, Christensenellaceae R-7 group, and Blautia. Collectively, these findings highlight the pronounced sex-dependent discrepancies in the microbial composition and metabolism within the small and large intestines of Jiangshan black pigs, providing new insights for precisely modulating the microbiota community and metabolism in pigs according to sex.