Alleviation of Oral Exposure to Aflatoxin B1-Induced Renal Dysfunction, Oxidative Stress, and Cell Apoptosis in Mice Kidney by Curcumin.

Aflatoxin B1 is a contaminant widely found in food and livestock feed, posing a major threat to human and animal health. Recently, much attention from the pharmaceutical and food industries has been focused on curcumin due to its strong antioxidant capacity. However, the therapeutic impacts and potential mechanisms of curcumin on kidney damage caused by AFB1 are still incomplete. In this study, AFB1 triggered renal injury in mice, as reflected by pathological changes and renal dysfunction. AFB1 induced renal oxidative stress and interfered with the Keap1-Nrf2 pathway and its downstream genes (CAT, SOD1, NQO1, GSS, GCLC, and GCLM), as manifested by elevated oxidative stress metabolites and reduced antioxidant enzymes activities. Additionally, AFB1 was found to increase apoptotic cells percentage in the kidney via the TUNEL assay, along with increased expression of Cyt-c, Bax, cleaved-Caspase-3, Caspase-9, and decreased expression of Bcl-2 at the transcriptional and protein levels; in contrast, for mice given curcumin, there was a significant reversal in kidney coefficient, biochemical parameters, pathological changes, and the expression of genes and proteins involved in oxidative stress and apoptosis. These results indicate that curcumin could antagonize oxidative stress and apoptosis to attenuate AFB1-induced kidney damage.

Curcumin mitigates aflatoxin B1-induced liver injury via regulating the NLRP3 inflammasome and Nrf2 signaling pathway.

Aflatoxins are produced as secondary metabolites by the toxigenic Aspergillus fungi. Among the aflatoxins, aflatoxin B1 (AFB1) is a common contaminant of global concern in human and animal food products. Prolonged exposure to AFB1 may provoke hepatocyte pyroptosis and oxidative stress, which leads to liver damage. Dietary polyphenols could protect the liver from a wide range of toxins. Curcumin, a polyphenolic substance derived from turmeric, is rich in pharmacological activity. The aim of this study was to systematically investigate the protective effects of curcumin against AFB1-induced liver injury in mice and to explore the possible molecular mechanisms. BALB/c mice received oral gavage of AFB1 (0.75 mg/kg) and curcumin (100 or 200 mg/kg) for 30 days. Our data demonstrated that curcumin attenuated AFB1-induced weight loss in mice and rescued liver injury by mitigating the alterations in pathology and liver function with AFB1 exposure. Curcumin reduced the accumulation of AFB1-DNA adducts in the liver and alleviated hepatotoxicity by inhibiting AFB1-induced oxidative stress and potentiating glutathione S-transferase (GST)-mediated phase II detoxification. In addition, curcumin significantly reduced the characteristic indices of AFB1-induced pyroptosis, such as the expression of mRNAs for genes related to NOD-like receptor protein 3 (NLRP3) inflammasome assembly and activation, the expression of key proteins (NLRP3, Caspase-1 and GSDMD). The release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the serum detected by ELISA was also significantly decreased. Notably, administration of curcumin upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its related downstream antioxidant molecules (SOD, CAT, HO-1, NQO1) and phase II detoxification enzyme-related molecules (GST, GSH, GSS, GCLC, GCLM) in the presence of AFB1 exposure. To summarize, our results indicated that curcumin could modulate the NLRP3 inflammasome and Nrf2 signaling pathways to attenuate AFB1-induced liver pyroptotic damage and oxidative stress.

Resveratrol Relieved Acute Liver Damage in Ducks (Anas platyrhynchos) Induced by AFB1 via Modulation of Apoptosis and Nrf2 Signaling Pathways.

The presence of aflatoxin B1 (AFB1) in feed is a serious threat to livestock and poultry health and to human food safety. Resveratrol (Res) is a polyphenolic compound with antioxidant, anti-apoptotic and other biological activities; however, it is not clear whether it can improve AFB1 induced hepatotoxicity. Therefore, this study was conducted to investigate the effects of dietary Res on liver injury induced by AFB1 and its mechanisms. A total of 270 one-day-old male specific pathogen free (SPF) ducks, with no significant difference in weight, were randomly assigned to three groups: the control group, the AFB1 group and the AFB1 + Res group, which were fed a basic diet, a basic diet and a basic diet containing 500 mg/kg Res, respectively. On the 70th day, the ducks in theAFB1 group and the AFB1+ 500 mg/kg Res group were given 60 µg/kg AFB1 via gavage. When comparing the AFB1 group and the AFB1 + Res group and also with the control group, AFB1 significantly increased liver damage, cytochrome P450 (CYP450) and AFB1-DNA adduct content, increased oxidative stress levels and induced liver apoptosis, which was improved by Res supplementation. In sum, the addition of Res to feed can increase the activity of the II-phase enzyme, activate the nuclear factor E2-related factor 2 (Nrf2) signal pathway, and protect ducks' livers from the toxicity, oxidative stress and inflammatory reaction induced by AFB1.

Effect of Dietary Curcumin Supplementation on Duck Growth Performance, Antioxidant Capacity and Breast Meat Quality.

This study aimed at examining the effects of curcumin supplementation on growth performance, antioxidant capacity, and meat quality of ducks. To investigate these effects, 600 healthy ducks were randomly assigned to four treatment groups with 10 replicates pens, and each pen contained 15 ducks. Ducks were fed a diet containing curcumin at levels of 0, 300, 400, and 500 mg kg-1 in different groups. The results demonstrated that curcumin supplementation is beneficial to the growth performance (p < 0.05) of ducks and antioxidant capacity (p < 0.05) of duck meat. In addition, dietary curcumin raised the meat quality of ducks, improving the meat color, increasing water-holding capacity, and inhibiting lipid and protein oxidation. In conclusion, the present study provides important insights into both the nutrient and qualities of ducks, finding that a dietary inclusion of 400-500 mg/kg of curcumin (kg-1) has the greatest effect.

The Critical Role of Tryptophan in the Antimicrobial Activity and Cell Toxicity of the Duck Antimicrobial Peptide DCATH.

Antimicrobial peptides (AMPs) have attracted more attention for their potential candidates for new antibiotic drugs. As a novel identified cathelicidin AMP from duck, dCATH owns broad-spectrum antimicrobial activities but with a noticeable toxicity. To explore dCATH-derived AMPs with reduced cell toxicity and improved cell selectivity, a series of truncated and tryptophan-replaced peptides of dCATH were designed. Two truncated peptides containing one of the two tryptophan (Trp) residues at the positions of 4 and 17 (W4 and W17) of dCATH, dCATH(1-16) and dCATH(5-20), showed strong antibacterial activity, but didn't show obvious hemolytic activity and cytotoxicity. The derived peptides not containing Trp didn't possess obvious antimicrobial activity, and their hemolytic and cytotoxic effect was also diminished. Also as evidence by Trp fluorescence experiment that existence of W4 and W17 was crucially important to the antimicrobial activity, hemolysis and cytotoxicity of dCATH, and one of the two Trp residues was competent and necessary to retain its antimicrobial activity. Antibacterial mechanism analysis showed that dCATH(1-16) and dCATH(5-20) killed bacterial cells by increasing permeability and causing a loss of membrane integrity. dCATH(1-16) and dCATH(5-20) possessed insignificant inhibitory activity against levels of IL-6, TNF-α, and NO in RAW 264.7 cells treated with LPS. In vivo, intraperitoneal administration of the two peptides significantly decreased mortality and provided protection against LPS-induced inflammation in mice challenged with lethal dose of LPS. The two peptides, dCATH(1-16) and dCATH(5-20), which possessed high antibacterial activity and cell selectivity, may herald development prospects as new antibacterial agents in the future.

Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma.

Tissue inhibitor metalloproteinase-1 (TIMP-1) is clinically associated with a poor prognosis for various cancers, but the roles of TIMP-1 in lung cancer metastasis are controversial. Our previous secretomic study revealed that TIMP-1 is highly abundant in high invasiveness cells of lung adenocarcinoma. In the current study, TIMP-1 abundances in primary lung adenocarcinoma tissues, as revealed by immunohistochemistry, are significantly higher in patients with lymph invasion and distant metastasis than in those without. Receiver operating characteristic curve analyses suggest 73.7 and 86.2 % accuracy to separate patients with lymph node and distant metastasis and those without, respectively. Moreover, we demonstrate that the expression level of TIMP-1 positively associates with cell mobility, invasiveness, and metastatic colonization. Most notably, the novel mechanism in which TIMP-1 facilitates metastatic colonization through the mediation of pericellular polyFN1 assembly was revealed. In summary, this study presents novel functions of TIMP-1 in promoting cancer metastasis and suggests TIMP-1 is a potential tissue biomarker for lymph invasion and distant metastasis of lung adenocarcinoma.

[Determination and fingerprint analysis of tetramethylpyrazine and ferulic acid in Ligusticum chuanxiong].

OBJECTIVE: To determine the contents of tetramethylpyrazine (TMP) and ferulic acid in Ligusticum chuanxiong from different producing areas and seasons. METHODS: The contents of TMP and ferulic acid were determined by HPLC, and then analyzed by Chromatographic Fingerprints. RESULTS: The contents of TMP and ferulic acid from different seasons were obviously different from each other. It was much higher in "laoxiong" than that in "naixiong". The similarity of fingerprints was high if the samples were collected from the same season, or the same areas, but not different seasons. CONCLUSIONS: The contents of TMP and ferulic acid were different from different producing areas. The evident variety of Ligusticum chuanxiong's fingerprints from different collecting seasons, Laoxiong and Naixiong, was not relevant for clinical use as the same medicine.