Toxicity and oxidative stress induced by T-2 toxin in cultured mouse Leydig cells

To explore the toxic mechanism of T-2 toxin on Leydig cells of mice, we would investigate the toxicity and oxidative stress induced by T-2 toxin in the cells. Leydig cells were isolated and cultured with control or T-2 toxin (10^?7 M, 10^?8 M, or 10^?9 M) for 24?h, then cells and supernatants were harvested to examine cell viability, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, expression of messenger RNA (mRNA) related to oxidative stress, malondialdehyde (MDA) content and DNA damage. The cell viability was evaluated in mouse Leydig cells by MTT assay, MDA content and SOD, GSH-Px and CAT activities were measured by routine kits, expression of mRNA related to oxidative stress were examined by quantitative real-time polymerase chain reaction (PCR), and DNA damage was investigated by comet assay. Leydig cells treated with T-2 toxin showed significant reductions in cell viability, SOD, GSH-Px and CAT activities, and expression of mRNA related to oxidative stress, and remarkable increases in MDA content and levels of DNA damage. This study proves that T-2 toxin is toxic to Leydig cells of mice. Furthermore, oxidative stress plays an important role in the above-mentioned negative effects of T-2 toxin.     

T-2 toxin initially activates caspase-2 and induces apoptosis in U937 cells

T-2 toxin, which belongs to a group of mycotoxins synthesized by Fusarium fungi that are widely encountered as natural contaminants, induced apoptosis with distinct morphological and biological features in U937 cells. The concentration of more than 10nM T-2 toxin affected cell viability, induced nuclear and DNA fragmentation and caspase-3 activation. Caspase-2, -3, -8, and -9 were activated during T-2 toxin-induced apoptosis. T-2 toxin neither inhibited mitochondrial respiratory chain complexes I-IV in isolated mitochondria nor decreased ATP levels in U937 cells. Both enzyme activity assay and Western blot analysis revealed that T-2 toxin activated caspase-2 earlier than caspase-3, -8, and -9. Caspase-2 inhibitor (VDVAD-CHO/fmk) and caspase-8 inhibitor (IETD-CHO/fmk) completely blocked the T-2 toxin-induced process of procaspase-3, while caspase-9 inhibitor (LEHD-CHO/fmk) did so less effectively. Caspase-2 inhibitor entirely blocked T-2 toxin-induced caspase-8, and -9 activation. These results clearly indicate that activation of caspase-2 is essential to T-2 toxin-induced apoptosis and that apoptotic signals are mainly transmitted via caspase-8 and caspase-3 rather than mitochondrial pathway.     

Potential Role of Individual and Combined Effects of T-2 Toxin,HT-2 Toxin and Neosolaniol on the Apoptosis of Porcine Leydig Cells

T-2 toxin usually co-occurs with HT-2 toxin and neosolaniol (NEO) in the grains and feed. Our previous studies found that T-2 toxin and its metabolites’ binary or ternary combination exposure to porcine Leydig cells (LCs) displayed synergism in certain range of dosage and cannot be predicted based on individual toxicity. However, the possible mechanism of these mycotoxins’ combined exposure to cell lesions remains unknown. Based on 50% cell viability, the mechanism of apoptosis in porcine Leydig cells was investigated after exposure to T-2, HT-2, NEO individual and binary or ternary combinations. Compared with control, the adenosine triphosphate (ATP) content decreased, reactive oxygen species (ROS) level increased, and mitochondrial membrane potential (MMP) decreased in all treated groups. Additionally, the cell apoptosis rates were significantly increased in test groups (p < 0.05), and the B-cell lymphoma 2 (Bcl-2) Associated X (Bax)/Bcl-2 ratio and the expression of caspase 3, caspase 8, cytochrome c (Cytc) in the treated group are all significantly higher than the control group. Moreover, the expression of Cytc and caspase 8 gene in NEO and T-2+NEO groups was significantly higher than that in other individual and combined groups. It can be concluded that the toxicities of T-2, HT-2, and NEO individually and in combination can induce apoptosis related to the oxidative stress and mitochondrial damage, and the synergistic effect between toxins may be greater than a single toxin effect, which is beneficial for assessing the possible risk of the co-occurrences in foodstuffs to human and animal health.     

Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin found in several food commodities worldwide. ZEA causes reproductive disorders, genotoxicity, and testicular toxicity in animals. However, little is known about the functions of apoptosis and autophagy after exposure to ZEA in Leydig cells. This study investigated the effects of ZEA on rat Leydig cells. Results showed that ZEA at different doses significantly inhibited the growth of Leydig cells by inducing apoptosis. ZEA treatment upregulated Bax expression, promoted cytochrome c release into the cytosol, and triggered mitochondria-mediated apoptosis. Consequently, caspase-9 and downstream effector caspase-3 were activated, followed by the cleavage of poly(ADP-ribose) polymerase (PARP), resulting in Leydig cell apoptosis. ZEA treatment also upregulated LC3-II and Beclin-1 expression, suggesting that ZEA induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast to other ZEA-treated groups. Autophagy delayed apoptosis in the ZEA-treated Leydig cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing ZEA-induced cytotoxicity.     

Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway

Zearalenone (ZEN) is a Fusarium mycotoxin that causes several reproductive disorders and genotoxic effects. This study demonstrated the involvement of endoplasmic reticulum (ER) stress in ZEN-induced mouse Leydig cell death. Our study showed that ZEN reduced cell proliferation in a murine Leydig tumour cell line in a dose-dependent manner. The involvement of apoptosis as a major cause of ZEN-induced cell death was further confirmed by the results of a caspase-3 activity assay, which showed a ZEN dose-dependent increase in cell death. Treatment of MLTC-1 and primary mouse Leydig cells with ZEN upregulated the expression of the ER stress-typical markers GRP78, CHOP and caspase-12 protein. Further, pre-treating the cells with 4-phenylbutyrate or knocking down GRP78 using lentivirus-encoded shRNA significantly diminished ZEN-induced apoptosis and inhibited the expression of CHOP and caspase-12. In summary, these results suggest that the activation of an ER stress pathway plays a key role in ZEN-induced apoptosis in the mouse Leydig cells.     

Penetration of [3H]T-2 toxin through excised human and guinea-pig skin during exposure to [3H]T-2 toxin adsorbed to corn dust

An in vitro test system was used to measure the penetration of [3H]T-2 toxin through human epidermis, human whole skin (isolated dermis and epidermis), and through guinea-pig whole skin. To simulate the conditions which occur when agricultural workers are exposed to corn dust contaminated with T-2 toxin, the epidermal surface of each skin preparation was dosed with [3H]T-2 toxin adsorbed onto corn dust. The applied dose was 3.27 to 4.75 mg of corn dust containing 18.2 ppm [3H]T-2 toxin. The rate of percutaneous penetration was determined by measuring the accumulation of radioactivity in the receptor fluid bathing the dermal side of the excised skin. The total penetrations (expressed as percentage dose) through isolated human epidermis, human whole skin and through isolated guinea-pig whole skin were 1.12 +/- 0.26% (mean +/- standard deviation), 0.33 +/- 0.07%, and 0.13 +/- 0.07% respectively. The radioactive compounds in the receptor fluid bathing the human whole skin corresponded to T-2 toxin (69%) and HT-2 toxin (25%), as determined by thin-layer chromatography. Thus T-2 toxin adsorbed onto corn dust can partition into and penetrate through excised human and guinea-pig skin.     

Effects of a trichothecene, T-2 toxin, on proliferation and steroid production by porcine granulosa cells

Fusarium mycotoxins, such as trichothecenes and zearalenone, are produced by molds and contaminate a large variety of grains and feedstuffs worldwide. Mycotoxins of Fusarium fungi include the trichothecenes, deoxynivalenol and T-2 toxin (T2), and zearalenone, and have been implicated in poor reproductive performance in pigs. However, direct ovarian effects of T2 toxin have not been reported. Therefore, porcine granulosa cells (GC) from small follicles (1-5 mm) were cultured for 2 days in 5% fetal bovine serum and 5% porcine serum-containing medium followed by 2 days in serum-free medium containing various doses of FSH, insulin-like growth factor-I and T2 (at various doses/combinations) to evaluate the influence of T2 on steroid production and cell proliferation. T2 at 1, 3, 30 and 300 ng/mL completely inhibited FSH plus IGF-I-induced estradiol production, whereas 0.3 ng/mL of T2 inhibited estradiol production by 40%. Progesterone production was less sensitive to the inhibitory effects of T2 with 0.3 ng/mL having no effect and 1 ng/mL inhibiting progesterone production by only 30%. At 30 and 300 ng/mL, T2 completely inhibited FSH plus IGF-I-induced progesterone production. The impact of T2 on the dose-response to IGF-I (0, 3, 10 and 30 ng/mL) was also evaluated; T2 blunted the stimulatory effect of 3-30 ng/mL of IGF-I on steroid production and cell proliferation. Serum-induced granulosa cell proliferation was decreased (P < 0.05) by 40% after 1 day and by 56% after 2 days of T2 treatment. The present studies indicate for the first time that T2 may be able to alter in growth of the granulosa layer within ovarian follicles in addition to their effect on steroidogenesis. In conclusion, T2 has potent direct dose-dependent effects on granulosa cell proliferation and steroidogenesis. These direct ovarian effects could be one mechanism whereby contaminating Fusarium mycotoxins in feedstuffs could impact reproductive performance in swine.     

l-carnitine protects rat hepatocytes from oxidative stress induced by T-2 toxin

Context: Oxidative stress and mitochondrial dysfunction are thought to be the main mechanism of T-2 toxin toxicity. T-2 toxin is the most potent trichothecene mycotoxin which is present in agricultural products. L-carnitine, besides its anti-oxidative properties, facilitates the transportation of long-chain fatty acids in to mitochondrial matrix. Objective: In this study we tested whether L-carnitine, an antioxidant and a facilitator for long-chain fatty acid transportation across mitochondrial membranes, could protect rat hepatocytes against toxicity induced by T-2 toxin. Materials and methods: L-carnitine in low and high doses (50 and 500?mg/kg) was administered for five consecutive days to male Wistar rats. Hepatocytes were isolated and freshly exposed to appropriate concentration of T-2 toxin for 2?h followed by oxidative stress and cell death evaluations. Results: Glutathione depletion, ROS overproduction and mitochondrial membrane potential collapse were determined under T-2 toxin exposure. Pretreatment with L-carnitine particularly at high-dose reduced toxicity and prevented the hepatocytes from abnormal caspase-3 activity and apoptosis. Conclusion: Low toxicity of L-carnitine and its mitochondrial protective effects promises an effective way to reduce or prevent the toxicity induced by certain environmental pollutants, including T-2 toxin.     

Toxicological interactions between the mycotoxins beauvericin, deoxynivalenol and T-2 toxin in CHO-K1 cells in vitro

Beauvericin (BEA), deoxynivalenol (DON) and T-2 toxin (T-2) are important food-borne mycotoxins that have been implicated in human health. In this study, the acute toxicity of individual and combined mycotoxins (BEA, DON and T-2) were tested in immortalized hamster ovarian cells (CHO-K1) at 24, 48 and 72 h of exposure, by the tetrazolium salt (MTT) and neutral red (NR) assays. The IC₅₀ values obtained for all mycotoxins by the MTT and NR assays ranged from 0.017 to 12.08 μM and from 0.042 to 17.22 μM, respectively. Both, individual and combined mycotoxins demonstrated a significant cytotoxic effect in CHO-K1 cells in a dose-dependent manner. When mycotoxins were assayed individually, T-2 showed the strongest IC₅₀ values (from 0.017 to 0.052 μM), by both endpoints tested, followed by DON (0.53-2.30 μM) and BEA, showing this last one, the weakest IC₅₀ values (from 2.77 to 17.22 μM). On the other hand, cytotoxicity interactions were evaluated by the isobologram method. In acute binary tests, DON + BEA (CI = 1.60-25.07) and DON + T-2 (CI = 1.74-7.71) showed antagonism at 24, 48 and 72 h of exposure. By contrast, the binary BEA + T-2 combination (CI = 0.35-0.78) showed synergism at all time of exposure tested. The tertiary BEA + DON + T-2 combination demonstrated synergism effect (CI = 0.47-0.86) after 24 and 48 h of exposure; however moderate antagonistic effect (CI = 1.14-1.60) was presented after 72 h of exposure at the lower doses. These results provide quantitative evidence regarding potentially important interactions between BEA, DON and T-2 depending of the time of exposure. The combination index-isobologram equation method can serve as a useful tool in food risk assessment. Due to the potent toxic effects of BEA, DON and T-2, its combined exposure might be an important trigger for development of several diseases in humans, from the mycotoxicological point of view, especially after long period of exposure time.     

T-2 toxin is hydroxylated by chicken CYP3A37

T-2 toxin (T-2) is an acute toxic trichothecene mycotoxin produced mainly by Fusarium species, detected in many crops including oats, wheat and barley, in animal feed and food. It is important to know the metabolic pathway and kinetics of T-2 in food animals given that T-2 can cause serious adverse effects on human health. In this study, we investigated the metabolic capacity of chicken CYP3A37 in the metabolism of T-2 using reconstituted bacteria produced enzymes. Our results showed that chicken CYP3A37 is able to convert T-2 to 3′-OH T-2 with an apparent K_m of 15.29 μM, and T-2 hydroxylation activity of CYP3A37 is strongly inhibited by ketoconazole (IC₅₀ = 0.11 μM). We also observed that chicken CYP3A37 can catalyze erythromycin N-demethylation, another CYP3A-specific activity. These findings imply that chicken CYP3A37 may have a broad substrate spectrum, similar to its human homologue CYP3A4.     

Comparative Cytotoxic Effects and Possible Mechanisms of Deoxynivalenol,Zearalenone and T-2 Toxin Exposure to Porcine Leydig Cells In Vitro

Mycotoxins such as zearalenone (ZEN), deoxynivalenol (DON) and T-2 toxin (T-2) are the most poisonous biological toxins in food pollution. Mycotoxin contaminations are a global health issue. The aim of the current study was to use porcine Leydig cells as a model to explore the toxic effects and underlying mechanisms of ZEN, DON and T-2. The 50% inhibitory concentration (IC₅₀) of ZEN was 49.71 μM, and the IC₅₀ values of DON and T-2 were 2.49 μM and 97.18 nM, respectively. Based on the values of IC₅₀, ZEN, DON and T-2 exposure resulted in increased cell apoptosis, as well as disrupted mitochondria membrane potential and cell cycle distribution. The results also showed that ZEN and DON significantly reduced testosterone and progesterone secretion in Leydig cells, but T-2 only reduced testosterone secretion. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein and 3β-hydroxysteroid dehydrogenase (3β-HSD) were significantly decreased by ZEN, DON and T-2; whereas the protein expression of cholesterol side-chain cleavage enzyme (CYP11A1) was only significantly decreased by ZEN. Altogether, these data suggest that the ZEN, DON and T-2 toxins resulted in reproductive toxicity involving the inhibition of steroidogenesis and cell proliferation, which contributes to the cellular apoptosis induced by mitochondrial injury in porcine Leydig cells.     

Cytotoxicity and related effects of T-2 toxin on cultured Vero cells.

T-2 toxin belongs to a group of mycotoxins synthesized by Fusarium fungi that are widely encountered as natural contaminants of certain important agricultural commodities particularly, cereals. Upon exposure, T-2 toxin causes severe human and animal diseases. It is considered to be a major causative agent in fatal alimentary toxic aleukia (ATA) in humans. In this study, cytotoxicity and apotosis induction by T-2 toxin was investigated in vitro on Vero cell line using the MTT and the neutral red viability assays, the induction of lipid peroxidation, the decrease of macromolecule levels (protein, DNA and RNA), DNA fragmentation and caspase-3-dependent apoptosis induction. Our results showed that T-2 toxin reduced cell viability correlated to an impairment of macromolecule levels. It also increased MDA formation, induced DNA fragmentation showed by DNA laddering patterns on agarose gel electrophoresis. This fragmentation is in relation with apoptosis induction which was confirmed by activation of caspase-3, and depletion of the mitochondrial membrane potential reflecting a mitochondrial dysfunction.     

Diosgenin induces apoptosis in HeLa cells via activation of caspase pathway

AIM: To investigate the mechanism of diosgenin-induced HeLa cell apoptosis. METHODS: HeLa cell growth was measured by MTT method. Apoptosis was detected by electron microscopy and agarose gel electrophoresis. Ratio of apoptotic cells was measured by APO-BRDU kit. Cell cycle distribution and changes of mitochondrial membrane potential were monitored by flow cytometry. Caspase activities were assayed by caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of mitochondrial Bcl-2 expression. RESULTS: Diosgenin inhibited HeLa cell growth. HeLa cells treated with diosgenin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-9 inhibitor (Ac-AAVALPAVLLALLAPLEHD-CHO), and caspase-3 inhibitor (z-DEVD-fmk) partially prevented diosgenin-induced apoptosis, but not caspase-8 inhibitor (z-IETD-fmk) and caspase-10 inhibitor (z-AEVD-fmk). Diosgenin caused reduction of mitochondrial membrane po     

Gastroprotective effects of amifostine in rats treated by T-2 toxin

Cytoprotector amifostine (AMI) was given in a dose of 50, 100 or 150?mg/kg ip in rats treated with several highly toxic doses of T-2 toxin. The best survival rate (24?h and 7?days after treatment) was obtained with AMI50 (50?mg/kg ip). After T-2 intoxication, a peak in the mean number of gastric lesions (petechiae and ulcerations) was reached on the third day (26.40?±?6.24). Administration of AMI50 reduced, almost completely, the total number of gastric lesions in rats acutely poisoned by 0.5 LD₅₀ T-2 (1.5?mg/kg sc), starting with day 1 after intoxication (5.60?±?3.42).     

Sinomenine induces apoptosis in RAW 264.7 cell- derived osteoclasts in vitro via caspase-3 activation

Aim： Sinomenine （SIN） is an alkaloid found in the roots and stems of Sinomenium acutum, which has been used to treat rheumatic arthritis in China and Japan. In this study we investigated the effects of SIN on osteoclast survival in vitro and the mechanisms of the actions. Methods： Mature osteoclasts were differentiated from murine monocyte/macrophage cell line RAW264.7 through incubation in the presence of receptor activator of NF-KB ligand （RANKL, 100 np=VmL） for 4 d. The cell viability was detected using the CCK-8 method. The survival and actin ring construction of the osteoclasts were scored using TRACP staining and phalloidin-FITC staining, respectively. The apoptosis of the osteoclasts was detected by DNA fragmentation and Hoechst 33258 staining, and the cell necrosis was indicated by LDH activity. The activation of caspase-3 in osteoclasts was measured using Western blotting and the caspase-3 activity colorimetric method. Results： SIN （0.25-2 mmol/L） inhibited the viability of mature osteoclasts in dose-dependent and time-dependent manners, but did not affect that of RAW264.7 cells. Consistently, SIN dose-dependently suppressed the survival of mature osteoclasts. The formation of actin ring, a marker associated with actively resorbing osteoclasts, was also impaired by the alkaloid. SIN （0.5 mmol/L） induced the apoptosis of mature osteoclasts, which was significantly attenuated in the presence of the caspase-3 inhibitor Ac-DEVD-CHO. SIN increased the cleavage of caspase-3 in mature osteoclasts in dose-dependent and time-dependent manners. Furthermore, SIN dose- dependently enhanced caspase-3 activity, which was blocked in the presence of Ac-DEVD-CHO. Conclusion： Sinomenine inhibits osteoclast survival in vitro through caspase-3-mediated apoptosis, thus it is a potential agent for treat- ing excessive bone resorption diseases.     

Effect of T-2 toxin-injected shrimp muscle extracts on mouse macrophage cells (RAW264.7)

Following intramuscular injections of 0.1?mL, 3?mg?kg^?1?BW^?1(1/10 LD₅₀) T-2 toxin (T-2), the tissue concentration of T-2 in shrimp was quantitatively detected using LC-MS/MS. The biological half-time (t_1/2) of T-2 in blood was 40.47?±?0.24?min. The highest number of intramuscular T-2 shrimp could tolerate when given at blood t_1/2 intervals was 4. The shrimps which were injected 5 T-2 died. The T-2 toxin highest accumulation was 0.471?±?0.012?ng?g^?1?BW^?1. The effect of toxic shrimp muscle subjected to different processing conditions (high pressure, trifluoroacetic acid, acid and alkali digestions, artificial digestive juice [to simulate exposure to gastric and intestinal juices]) on mouse macrophage cells (RAW267.4) were evaluated by the MTT assay. The inhibition ratio of 2% muscle extract on RAW267.4 was 85.70?±?2.63%. The immunocytotoxicity of muscle extracts to RAW264.7 was highest in muscle extracts subjected to physical and chemical digestion (high pressure >?NaOH?> trifluoroacetic acid >?0.02 M HCl?>?0.2 M HCl?>?controls), and also artificial digestion (artificial intestinal juice >?artificial gastric juice >?N type intestinal juice >?N type gastric liquid >?controls). Results showed that high-pressure and artificial intestinal juice were most effective in the release of modified T-2 to free T-2 thus enhancing toxicity. These results can be interpreted as measurement of T-2 in food being of little value because of enhanced toxicity of T-2-contaminated food as they pass through the gastrointestinal tract.     

Bufalin induces apoptosis via mitochondrial ROS-mediated caspase-3 activation in HCT-116 and SW620 human colon cancer cells

Objective: Bufalin has been reported to kill various types of cancer including human colorectal cancer. Our previous study demonstrated that bufalin induced cell death via autophagy in HT-29 and Caco-2 colon cancer cells, but the action of bufalin remains unclear. This study was conducted to investigate the role of bufalin in other colon cancer HCT-116 and SW620 cells as well as its potential mechanism.

Methods: The effect of bufalin in HCT-116 and SW620 colon cancer cells was detected by assessing cell viability and cell death. Apoptotic cells were analyzed by Western blot and trypan blue dye exclusion assay. Mitochondrial ROS production was analyzed by flow cytometry after DCFDA and DHR-123 staining. The potential mechanism was investigated via pharmacological inhibitors.

Results: Bufalin had high potency against HCT-116 and SW620 cells with IC50 values of 12.823?±?1.792?nM and 26.303?±?2.498?nM in HCT-116 and SW620 cells, respectively. Bufalin decreased cell viability, increased cell death as well as caspase-3 downstream target (cleaved PARP) accumulation, and these actions were significantly blocked by pan-caspase inhibitor zVAD-FMK. Mechanistically, ROS production, but neither the NAD(P)H oxidase, AMPK, ERK nor p38, is responsible for bufalin-induced apoptotic cell death. Moreover, bufalin-induced ROS generation is derived from mitochondria.

Conclusion: Bufalin significantly induces apoptosis in HCT-116 and SW620 colon cancer cells via mitochondrial ROS-mediated caspase-3 activation. We believe that our novel findings will greatly alter our current understanding on the anti-cancer mechanism of bufalin in colon cancer cells and will pave the way for further exploiting the clinical application.     

T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-gamma responses

Trichothecenes are exquisitely toxic to the gastrointestinal (GI) tract and leukocytes and thus are likely to impair gut immunity. The purpose of this research was to test the hypothesis that the Type A trichothecene T-2 toxin interferes with the gut mucosal immune response to enteric reovirus infection. Mice were exposed i.p. first to 1.75 mg/kg bw T-2 and then 2 h later with 3 x 10(7) plaque-forming units of reovirus serotype 1, strain Lang (T1/L). As compared to vehicle-treated control, T-2-treated mice had dramatically elevated intestinal plaque-forming viral titers after 5 days and failed to completely clear the virus from intestine by 10 days. Levels of reovirus lambda2 core spike (L2 gene) RNA in feces in T-2-treated mice were significantly higher at 1, 3, 5, and 7 days than controls. T-2 potentiated L2 mRNA expression in a dose-dependent manner with as little as 50 microg/kg of the toxin having a potentiative effect. T-2 exposure transiently suppressed induction of reovirus-specific IgA in feces (6 and 8 days) as well as specific IgA and IgG2a in serum (5 days). This suppression corresponded to decreased secretion of reovirus-specific IgA and IgG2a in Peyer's patch (PP) and lamina propria fragment cultures prepared 5 days after infection. T-2 suppressed IFN-gamma responses in PP to reovirus at 3 and 7 days as compared to infected controls whereas IL-2 mRNA concentrations were unaffected. PP IL-6 mRNA levels were increased 2-fold 2 h after T-2 treatment, but no differences between infected T-2-exposed and infected vehicle-treated mice were detectable over the next 7 days. Overall, the results suggest that T-2 toxin increased both the extent of GI tract reovirus infection and fecal shedding which corresponded to both suppressed immunoglobulin and IFN-gamma responses.     

Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2 ／ Bax and activating caspase-3 ／ ICAD pathway

INTRODUCTIONHerbal medicine, Donglingcao (rabdosiarubescens), has been traditionally used in China for thetreatment of various diseases such as leukemia.Oridonin (Fig 1) is a diterpenoid compound isolated fromRabdosia rubescens (hemsl). It has various pharmaco-logical and physiological effects such as anti-inflammation, anti-bacteria, anti-tumor[1-3] and has beenused for the treatment of human cancers, especiallyFig 1. Chemical structure of oridonin.esophageal carcinoma[4]. This comp…