curcumin and quinocetone

The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress, mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor -kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX, a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Blotting, Western; Cells, Cultured; Curcumin; Heme Oxygenase-1; Hepatocytes; Humans; Inflammation; L-Lactate Dehydrogenase; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Quinoxalines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

The aim of this study was to evaluate the effect of dietary curcumin supplementation on growth performance and intestinal mucosal barrier function of weaned piglets. Fifty piglets, weaned at 21±2 days of age, were randomly allotted to five treatments for 21 days. The dietary treatments were the control (basal diet), and the basal diet supplemented with 50mg/kg quinocetone, or 200 mg/kg, 300 mg/kg or 400mg/kg curcumin. The piglets were housed in individual pens and orally challenged with enterotoxigenic Escherichia coli (ETEC) during the preliminary trial period. The jejunal morphology and histology analysis were detected under light microscope. The plasma D-lactate and diamine oxidase (DAO) were determined by using enzymatic spectrophotometric assay. Immunohistochemistry assays were used to examine secretory immunoglobulin (sIgA) protein expression. Real-time PCR was used to determine mRNA levels of cytokine and Toll-like receptor 4 (TLR4) in jejunal mucosa. The results showed that, compared with the control, dietary addition of 300 mg/kg or 400 mg/kg curcumin decreased (P<0.05) feed/gain ratio and crypt depth, improved (P<0.05) villus height and villus height:crypt depth ratio, reduced (P<0.05) plasma D-lactate and DAO activity, up-regulated the protein expression of sIgA (P<0.05), increased (P<0.05) the number of goblet cells (GCs) and reduced (P<0.05) the number of intraepithelial lymphocytes (IELs). The mRNA levels of interleukin 1β (IL-1β) and TLR4 and tumor necrosis factor α (TNF-α) were also decreased (P<0.05), but mRNA level of interleukin 10 (IL-10) was increased (P<0.05). There was no difference in the above parameters between the 300 mg/kg and 400 mg/kg curcumin groups. Pigs fed with 50 mg/kg quinocetone also decreased (P<0.05) feed/gain ratio, increased villus height:crypt depth ratio (P<0.05), and reduced (P<0.05) crypt depth and mRNA levels of TLR4. In conclusion, curcumin and the quinocetone have similar effects in improving piglet growth, but dietary addition of 300 mg/kg or 400 mg/kg curcumin was more effective than quinocetone in improving intestinal mucosal barrier integrity, morphology, and immune status of weaned pigs. This indicates that curcumin could be used as a potential feed additive replacing quinocetone in weaned piglets.

Topics: Animals; Curcumin; Cytokines; Dietary Supplements; Enterocolitis; Escherichia coli; Escherichia coli Infections; Growth and Development; Immunity, Innate; Immunoglobulin A; Intestinal Mucosa; Jejunum; Quinoxalines; Swine; Weaning

Quinocetone (QCT), a new quinoxaline 1,4-dioxides, has been used as antimicrobial feed additive in China. Potential genotoxicity of QCT was concerned as a public health problem. This study aimed to investigate the protective effect of curcumin on QCT-induced oxidative stress and genotoxicity in human hepatocyte L02 cells. Cell viability and intracellular reactive oxygen species (ROS), biomarkers of oxidative stress including superoxide dismutase (SOD) activity and glutathione (GSH) level were measured. Meanwhile, comet assay and micronucleus assay were carried out to evaluate genotoxicity. The results showed that, compared to the control group, QCT at the concentration ranges of 2-16 μg/mL significantly decreased L02 cell viability, which was significantly attenuated with curcumin pretreatment (2.5 and 5 μM). In addition, QCT significantly increased cell oxidative stress, characterized by increases of intracellular ROS level, while decreased endogenous antioxidant biomarkers GSH level and SOD activity (all p < 0.05 or 0.01). Curcumin pretreatment significantly attenuated ROS formation, inhibited the decreases of SOD activity and GSH level. Furthermore, curcumin significantly reduced QCT-induced DNA fragments and micronuclei formation. These data suggest that curcumin could attenuate QCT-induced cytotoxicity and genotoxicity in L02 cells, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, consumption of curcumin may be a plausible way to prevent quinoxaline 1,4-dioxides-mediated oxidative stress and genotoxicity in human or animals.

Topics: Antimutagenic Agents; Antioxidants; Cell Line; Cell Survival; Comet Assay; Curcumin; DNA; DNA Damage; Glutathione; Hepatocytes; Humans; Micronucleus Tests; Oxidative Stress; Quinoxalines; Reactive Oxygen Species; Superoxide Dismutase