ascorbic-acid and deoxynivalenol

Type B trichothecene mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially

Topics: Animals; Antioxidants; Ascorbic Acid; Jejunum; Lipid Metabolism; Male; p38 Mitogen-Activated Protein Kinases; Saccharomyces cerevisiae; Signal Transduction; Swine; Transcriptome; Trichothecenes

The in vitro effects of 2 representative mycotoxins, T-2 toxin and deoxynivalenol (DON), of trichothecene group on the electron transport system (ETS) of mitochondria in rat cardiomyocytes were investigated by measuring oxygen consumption rates (OCR). The ATP-linked OCR and the reserve capacity (RC) of the mitochondria ETS were quantified by a "mitochondria stress test" which was estimated by the OCR responses to oligomycin and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, with an extracellular flux analyzer. The basal OCR was significantly inhibited by the application of T-2 toxin at concentrations of 6 × 10⁻¹ to 6 × 10⁻⁵ μM and DON at concentrations of 0.78 to 100 μM for 24 hr. The threshold of cardiomyocyte toxicity was estimated to be between 6.0 × 10⁻⁶ and 6.0 × 10⁻⁵ μM for T-2 toxicity on both ATP-linked OCR and RC and between 0.39 and 0.78 μM on ATP-linked OCR or between 1.56 and 3.13 μM on RC for DON. The decrease in OCR of cardiomyocytes exposed to T-2 toxin with a concentration of 6.0 × 10⁻³ and 6.0 × 10⁻⁴ μM was significantly inhibited by antioxidants, catalase and vitamin C. In conclusion, the present study demonstrated, through the direct and real-time measurement of respiratory function in mitochondria, that a marked inhibition of mitochondrial ETS function in cardiomyocytes was induced by T-2 toxin and DON and that the mitochondrial dysfunction by T-2 toxin was largely associated with oxidative stress.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Ascorbic Acid; Catalase; Cells, Cultured; Dose-Response Relationship, Drug; Electron Transport; Mitochondria; Myocytes, Cardiac; Oxygen Consumption; Rats, Sprague-Dawley; T-2 Toxin; Trichothecenes

To explore the effects of Vitamin C (Vit C) on the apoptosis and proliferation inhibition of human peripheral blood mononuclear cells (HPBMCs) induced by deoxynivalenol (DON) in vitro.. The effects of Vit C pretreatment at different dosages (25 micromol/L and 100 micromol/L) on apoptosis, apoptosis related genes expression and proliferation inhibition of HPBMCs induced by DON were evaluated with cell culture, flow cytometric DNA analysis and Western blotting.. Flow cytometry (FCM) analysis showed that the apoptosis rate of HPBMCs in 2000 microg/L DON group was (28.82 +/- 1.67)%, which was significantly higher than that in control group (14.07 +/- 0.70, P < 0.05). Compared with DON group, the apoptosis rate of HPBMCs in 25 micromol/L Vit C pretreatment group was significantly decreased (28.82 +/- 1.67)% vs (22.39 +/- 1.05)%, P < 0.05, while that in 100 micromol/L Vit C pretreatment group was obviously increased (36.07 +/- 2.92)%, P < 0.05. Western blotting analysis showed that the expression of Bax and Caspase-3 up-regulated by DON was markedly decreased, while the expression of Bcl-2 down-regulated by DON was increased by 25 micromol/L Vit C pretreatment (P < 0.05). 100 micromol/L Vit C pretreatment could further increase the expression of Bax and Caspase-3 of HPBMCs induced by DON, while no significant effects on the Bcl-2 expression induced by DON were seen. FCM analysis showed that the proliferation index of HPBMCs in Vit C pretreatment groups at different dosages was all dramatically increased as compared with that in DON groups (P < 0.05).. 25 micromol/L Vit C pretreatment could at certain extent inhibit the apoptosis and reverse the abnormal expression of apoptosis related genes of HPBMCs induced by DON in vitro, while 100 micromol/L Vit C pretreatment could further increase the apoptosis rate of HPBMCs induced by DON. Vit C pretreatment could reverse the proliferation inhibition of HPBMCs induced by DON in vitro.

Topics: Apoptosis; Ascorbic Acid; Cell Proliferation; Cells, Cultured; Humans; Monocytes; Trichothecenes

To explore the putative effects of Vitamin C (Vit C) on inhibition of human leucocyte antigen class I (HLA-I) expression of human peripheral blood mononuclear cells (HPBMCs) induced by deoxynivalenol (DON) in vitro.. The effects of Vit C on the changes of HLA-I expression of HPBMCs induced by DON in vitro were evaluated with cell culture, flow cytometry (FCM), Western blotting and immunocytochemical methods.. FCM analysis showed that HLA-I expression of HPBMCs in DON treated cells was significantly lower than that in controls (FI 0.88 +/- 0.02 vs 1.00 +/- 0.03, P < 0.05). As compared with DON group, the HLA-I expressions of HPBMCs in the two Vit C (25 micromol/L and 100 micromol/L) pretreatment groups were all significantly increased (1.15 +/- 0.06 and 1.10 +/- 0.02 vs 0.88 +/- 0.02, P < 0.05). Exposure to different dosage of Vit C alone could dramatically increase the expression of HLA-I of HPBMCs in vitro as compared with that in the normal control (FI for 25 micromol/L and 100 micromol/L Vit C treatment group was 1.28 +/- 0.03 and 1.25 +/- 0.05 respectively, P < 0.05). Immunocytochemical results showed that the percentages of HLA-I positive expression of HPBMCs in Vit C pretreatment groups at different dosages were significantly higher than those in DON group (70.10 +/- 6.90)%, (64.50 +/- 5.50)% vs (42.20 +/- 4.30)%, P < 0.05. Western blotting confirmed the results of FCM and immunocytochemistry.. Vitamin C pretreatment at different dosages could reverse at some extent the inhibitive effects of DON on HLA-I expression of HPBMCs.

Topics: Ascorbic Acid; Cells, Cultured; Flow Cytometry; Histocompatibility Antigens Class I; Humans; Monocytes; Trichothecenes

An experiment was conducted on rats to investigate the capacity of antioxidants to protect against acute toxicity caused by DON or T-2 toxin. Male rats were fed two different feeds. One group received a feed deficient in vitamins C and E and selenium, whereas the other group was fed with a feed enriched in antioxidants. After two weeks, selected groups of rats were administered orally a single dose of DON or T-2 toxin. After the treatment with mycotoxins, all rats were decapitated. The livers were analyzed for TBARS values, hepatic GSH content and for the activities of CyP-450, CAT, SOD and GSH-TR. Increases in lipid peroxides of 21% and 268% were observed in those rats which did not receive the supplement of antioxidants and which were administered DON or T-2 toxin, respectively. There was no significant increases in the TBARS values in the groups receiving DON with selenium and vitamins, but increases of 57% and 79% were recorded in the groups administered T-2 toxin and antioxidants. Furthermore, in the groups fed the deficient feed and administered DON or T-2 toxin, the lipid peroxidation increased by 33% and 307%, respectively. No mortality, and a lower number of intoxicated animals were observed in rats fed a diet supplemented with antioxidants. Significant decreases of GSH, CAT, SOD, CyP-450 and GSH-TR were recorded in treated rats receiving the deficient feed. The results of this study demonstrate that trichothecenes stimulate lipid peroxidation with consequent decrease of GSH content, but that the dietary use of selenium, alpha-tocopherol and ascorbic acid provides protection against acute toxicosis caused by DON or T-2 toxin.

Topics: Animals; Ascorbic Acid; Free Radicals; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Selenium; T-2 Toxin; Trichothecenes; Vitamin E