The Detoxification Effects of Melatonin on Aflatoxin-Caused Toxic Effects and Underlying Molecular Mechanisms.

Aflatoxins (AFTs) are a form of mycotoxins mainly produced by and , which are common contaminants in various agricultural sources such as feed, milk, food, and grain crops. Aflatoxin B1 (AFB1) is the most toxic one among all AFTs. AFB1 undergoes bioactivation into AFB1-8,9-epoxide, then leads to diverse harmful effects such as neurotoxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, nephrotoxicity, and immunotoxicity, with specific molecular mechanisms varying in different pathologies.

Molecular insights of T-2 toxin exposure-induced neurotoxicity and the neuroprotective effect of dimethyl fumarate.

T-2 toxin, a potent environmental pollutant, has been proved to stimulate neuroinflammation, while the connection between T-2 toxin and pyroptosis remain elusive. Dimethyl fumarate (DMF), recently identified as a neuroprotectant and pyroptosis inhibitor, has potential therapeutic applications that are underexplored. Based on present study in vitro and vivo, we demonstrated that T-2 toxin induced the activation of NLRP3-Caspase-1 inflammasome in hippocampal neurons.

S2 subunit plays a critical role in pathogenesis of TW-like avian coronavirus infectious bronchitis virus.

To investigate the critical role of the S gene in determining pathogenesis of TW-like avian infectious bronchitis virus (IBV), we generated two recombinant IBVs (rGD and rGD) by replacing either the S1 or S2 region of GD strain with the corresponding regions from an attenuated vaccine candidate aGD strain. The virulence and pathogenicity of these recombinant viruses was assessed both in vitro and in vivo. Our results indicated the mutations in the S2 region led to decreased virulence, as evidenced by reduced virus replication in embryonated chicken eggs and chicken embryonic kidney cells as well as observed clinical symptoms, gross lesions, microscopic lesions, tracheal ciliary activity, and viral distribution in SPF chickens challenged with recombinant IBVs.

Paeoniflorin recued hepatotoxicity under zinc oxide nanoparticles exposure via regulation on gut-liver axis and reversal of pyroptosis.

The risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF).

Sesquiterpenes from two Compositae plants as promising inhibitors to nuclear hormone receptor 3 of Tribolium castaneum.

Essential oils (EOs) and their volatile secondary metabolites have been proved to be effective on storage pests control, while restricted on the application due to unclear mechanism. Molecular dynamics (MD) simulations and binding free energies analysis provided an effective approach to reveal mechanism on conformational calculation. In this work, the insecticidal and repellent capacities of Praxelis clematidea and Ageratum houstonianum oils and their main components identified by gas chromatography-mass spectrometry (GC-MS) were scientifically measured.

Spatial distribution and comparative analysis of alkaloids in Fuzi using DESI-MSI and UHPLC-QTOF-MS.

poisoning is a major type of poisoning caused by herbal medicines in many countries. However, despite its toxicity, is still used because of its therapeutic value. Fuzi, the lateral root of , is one of the most important pharmacological parts.

TFEB coordinates autophagy and pyroptosis as hepatotoxicity responses to ZnO nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) have drawn serious concerns about their biotoxicity due to their extensive applications in biological medicine, clinical therapeutic, daily chemical production, food and agricultural additives. In our present study, we clarified hepatotoxic mechanism of ZnO NPs through investigating the crosstalk between autophagy and pyroptosis, a remaining enigma in hepatocyte stimulated by ZnO NPs. Based on the effects of autophagy intervention by Rapamycin (Rap) and 3-Methyladenine (3-MA), and the observation of pyroptosis morphology and related indexes, the autophagy and pyroptosis simultaneously initiated by ZnO NPs were interrelated and the autophagy characterized by autophagosome production and increased expression of autophagy proteins was identified as a protective response of ZnO NPs against pyroptosis.

Oxidative stress-related canonical pyroptosis pathway, as a target of liver toxicity triggered by zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in the fields of daily necessities, clinical diagnosis, drug delivery and agricultural production. The improper use of ZnO NPs could pose a risk to ecological environment and public health. Liver has been known as a critical toxic target of ZnO NPs.

Lethality of Zinc Oxide Nanoparticles Surpasses Conventional Zinc Oxide via Oxidative Stress, Mitochondrial Damage and Calcium Overload: A Comparative Hepatotoxicity Study.

Zinc oxide nanoparticles (ZnO NPs) with high bioavailability and excellent physicochemical properties are gradually becoming commonplace as a substitute for conventional ZnO materials. The present study aimed to investigate the hepatotoxicity mechanism of ZnO NPs and traditional non-nano ZnO particles, both in vivo and in vitro, and identify the differences in their toxic effects. The results showed that the extent and conditions of zinc ion release from ZnO NPs were inconsistent with those of ZnO.

Food-Origin Mycotoxin-Induced Neurotoxicity: Intend to Break the Rules of Neuroglia Cells.

Mycotoxins are key risk factors in human food and animal feed. Most of food-origin mycotoxins could easily enter the organism and evoke systemic toxic effects, such as aflatoxin B1 (AFB1), ochratoxin A (OTA), T-2 toxin, deoxynivalenol (DON), zearalenone (ZEN), fumonisin B1 (FB1), and 3-nitropropionic acid (3-NPA). For the last decade, the researches have provided much evidences in vivo and in vitro that the brain is an important target organ on mycotoxin-mediated neurotoxic phenomenon and neurodegenerative diseases.

Targeting HMGB1 inhibits T-2 toxin-induced neurotoxicity via regulation of oxidative stress, neuroinflammation and neuronal apoptosis.

T-2 toxin, a food-derived mycotoxin, has been identified as a neurotoxin. Nonetheless, T-2 toxin-induced neuroinflammation has never been revealed. As an important therapeutic target for inflammatory diseases and cancers, the role of high mobility group B1 (HMGB1) in mycotoxin-mediated neurotoxicity remains a mystery.

Identification of Plant Soot as Novel Safe Feed Additive: Evaluation of 90-Day Oral Toxicity and Prenatal Developmental Toxicity in Rats.

Plant soot, as a novel feed additive, could not only improve digestive function but also adsorb mycotoxins and inhibit bacterial infections. The subchronic toxicity and prenatal developmental effects of plant soot were studied for the first time. Our results indicated that there was no subchronic toxicity in the range of 2,000-50,000 mg/kg plant soot added in the feed, and there was no significant difference in reproductive function, embryo development, and teratogenicity between the pregnant rats exposed to 312.

Olaquindox-Induced Liver Damage Involved the Crosstalk of Oxidative Stress and p53 In Vivo and In Vitro.

Olaquindox (OLA), a member of the quinoxaline-N,N-dioxide family, has been widely used as a growth-promoting feed additive and treatment for bacterial infections. The toxicity has been a major concern, and the precise molecular mechanism remains poorly understood. The present study was aimed at investigating the roles of oxidative stress and p53 in OLA-caused liver damage.

Curcumin Ameliorates Copper-Induced Neurotoxicity Through Inhibiting Oxidative Stress and Mitochondrial Apoptosis in SH-SY5Y Cells.

Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot.

Molecular mechanism of olaquindox-induced hepatotoxicity and the hepatic protective role of curcumin.

Olaquindox (OLA) is a chemosynthetic growth promoter, which could promote the treatment of bacterial infections and improve feed energy efficiency. Hepatotoxicity is still a poor feature associated with the adverse effects of OLA. The present study aimed to investigate the molecular mechanism of OLA-induced hepatotoxicity and the protective role of curcumin in mice and HepG2 cells.

Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways.

The precise pathogenic mechanism in Cu exposure-cause nephrotoxicity remains unclear. This study investigated the underlying molecular mechanism of copper sulfate (CuSO)-induced nephrotoxicity. Mice were treated with CuSO at 50, 100, 200 mg/kg/day or co-treated with CuSO (200 mg/kg/day) and 4-phenylbutyric acid (4-PBA, 100 mg/kg/day) for 28 consecutive days.

Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis.

This is the first study to investigate the hepatoprotective effect of CQ on acute liver injury caused by carbon tetrachloride (CCl) in a murine model and the underlying molecular mechanisms. Ninety-six mice were randomly divided into the control (n = 8), CQ (n = 8), CCl (n = 40), and CCl + CQ (n = 40) treatment groups. In the CCl group, mice were intraperitoneally (i.

DIDS inhibits overexpression BAK1-induced mitochondrial apoptosis through GSK3β/β-catenin signaling pathway.

Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo.

ROS-mediated oligomerization of VDAC2 is associated with quinocetone-induced apoptotic cell death.

Quinocetone (QCT) has been approved and widely used as an animal feed additive in China since 2003. However, investigations indicate that QCT shows potential toxicity both in vitro and in vivo. Although voltage dependent anion channel 1 (VDAC1) involved in regulating QCT-induced apoptotic cell death has been established, the role of voltage dependent anion channel 2 (VDAC2) in QCT-induced toxicity remains unclear.

Critical role of p21 on olaquindox-induced mitochondrial apoptosis and S-phase arrest involves activation of PI3K/AKT and inhibition of Nrf2/HO-1pathway.

Olaquindox, a quinoxaline 1,4-di-N-oxide, is known as an antibacterial agent and feed additive to treat bacterial infections and promote animal growth. However, the potential mechanism of toxicity is still unknown. The present study aims to explore the molecular mechanism of p21 on olaquindox-induced mitochondrial apoptosis and S-phase arrest in human hepatoma G2 cells (HepG2).

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells.

Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner.

Quinocetone induces mitochondrial apoptosis in HepG2 cells through ROS-dependent promotion of VDAC1 oligomerization and suppression of Wnt1/β-catenin signaling pathway.

Quinocetone (QCT) has been used as an animal feed additive in China since 2003. However, investigations indicate that QCT has potential toxicity due to the fact that it shows cytotoxicity, genotoxicity, hepatotoxicity, nephrotoxicity and immunotoxicity in vitro and animal models. Although QCT-induced mitochondrial apoptosis has been established, the molecular mechanism remains unclear.

GADD45a Regulates Olaquindox-Induced DNA Damage and S-Phase Arrest in Human Hepatoma G2 Cells via JNK/p38 Pathways.

Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear.

Curcumin Attenuates Colistin-Induced Neurotoxicity in N2a Cells via Anti-inflammatory Activity, Suppression of Oxidative Stress, and Apoptosis.

Neurotoxicity is an unwanted side-effect seen in patients receiving therapy with the "last-line" polymyxin antibiotics. This is the first study to show that colistin-induced neurotoxicity in neuroblastoma-2a (N2a) cells gives rise to an inflammatory response involving the IL-1β/p-IκB-α/NF-κB pathway. Pretreatment with curcumin at 5, 10, and 20 μM for 2 h prior to colistin (200 μM) exposure for 24 h, produced an anti-inflammatory effect by significantly down-regulating the expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2), phosphorylation of the inhibitor of nuclear factor-kappa B (NF-κB) (p-IκB)-α, and concomitantly NF-κB levels.

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway.

Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells.