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Abstract Cisplatin‐associated acute kidney injury (AKI) is a severe clinical syndrome that significantly restricts the chemotherapeutic application of cisplatin in cancer patients. Ferroptosis, a newly characterized programmed cell death driven by the lethal accumulation of lipid peroxidation, is widely reported to be involved in the pathogenesis of cisplatin‐associated AKI. Targeted inhibition of ferroptosis holds great promise for developing novel therapeutics to alleviate AKI. Unfortunately, current ferroptosis inhibitors possess low bioavailability or perform non‐specific accumulation in the body, making them inefficient in alleviating cisplatin‐associated AKI or inadvertently reducing the anti‐tumor efficacy of cisplatin, thus not suitable for clinical application. In this study, a novel selenium nanomaterial, polyacrylic acid‐coated selenium‐doped carbon dots (SeCD), is rationally developed. SeCD exhibits high biocompatibility and specifically accumulates in the kidney. Administration of SeCD effectively scavenges broad‐spectrum reactive oxygen species and significantly facilitates GPX4 expression by releasing selenium, resulting in strong mitigation of ferroptosis in renal tubular epithelial cells and substantial alleviation of cisplatin‐associated AKI, without compromising the chemotherapeutic efficacy of cisplatin. This study highlights a novel and promising therapeutic approach for the clinical prevention of AKI in cancer patients undergoing cisplatin chemotherapy.

Abstract Background Deoxynivalenol (DON) is a widespread issue for feed and food safety, leading to animal and human health risks. The objective of this study was to determine whether ferroptosis is involved in DON-induced intestinal injury in piglets. Three groups of 21-day-old male weanling piglets (n = 7/group) were fed a control diet, or diet adding 1.0 or 3.0 mg DON/kg. At week 4, serum and small intestines were collected to assay for biochemistry, histology, redox status and ferroptosis-related genes expression. In addition, the involvement of ferroptosis and the role of FTL gene in DON-induced cell death were further verified in the IPEC-J2 cells. Results Compared to the control, dietary supplementation of DON at 1.0 and 3.0 mg/kg induced different degrees of damage in the duodenum, jejunum and ileum, and increased (P < 0.05) serum lipopolysaccharide concentration by 46.2%–51.4%. Dietary DON supplementation at 1.0 and (or) 3.0 mg/kg increased (P < 0.05) concentrations of malondialdehyde (17.4%–86.5%) and protein carbonyl by 33.1%–92.3% in the duodenum, jejunum and ileum. In addition, dietary supplemented with DON upregulated (P < 0.05) ferroptotic gene (DMT1) and anti-ferroptotic genes (FTL and FTH1), while downregulated (P < 0.05) anti-ferroptotic genes (FPN, FSP1 and CISD1) in the duodenum of the porcine. Furthermore, the in vitro study has demonstrated that deferiprone, a potent ferroptotic inhibitor, mitigated (P < 0.05) DON-induced cytotoxicity in porcine small intestinal IPEC-J2 cells. Additionally, deferiprone prevented or alleviated (P < 0.05) the dysregulation of ferroptosis-related genes (ACSL4 and FTL) by DON in IPEC-J2 cells. Moreover, specific siRNA knockdown FTL gene expression compromised the DON-induced cell death in IPEC-J2 cells. Conclusions In conclusion, this study revealed that ferroptosis is involved in DON-induced intestinal damage in porcine, and sheds a new light on the toxicity of DON to piglets.

Abstract Mycotoxins are toxic secondary metabolites produced by filamentous fungi that are commonly detected as natural contaminants in agricultural commodities worldwide. Mycotoxin exposure can lead to mycotoxicosis in both animals and humans when found in animal feeds and food products, and at lower concentrations can affect animal performance by disrupting nutrient digestion, absorption, metabolism, and animal physiology. Thus, mycotoxin contamination of animal feeds represents a significant issue to the livestock industry and is a health threat to food animals. Since prevention of mycotoxin formation is difficult to undertake to avoid contamination, mitigation strategies are needed. This review explores how the mycotoxins aflatoxins, deoxynivalenol, zearalenone, fumonisins and ochratoxin A impose nutritional and metabolic effects on food animals and summarizes mitigation strategies to reduce the risk of mycotoxicity.

Abstract Mycotoxins are secondary metabolites of different species of fungi. Aflatoxin B1 (AFB1), deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) are the main mycotoxins contaminating animal feedstuffs. These mycotoxins can primarily induce hepatotoxicity, immunotoxicity, neurotoxicity and nephrotoxicity, consequently cause adverse effects on the health and performance of animals. Therefore, physical, chemical, biological and nutritional regulation approaches have been developed as primary strategies for the decontamination and detoxification of these mycotoxins in the feed industry. Meanwhile, each of these techniques has its drawbacks, including inefficient, costly, or impractically applied on large scale. This review summarized the advantages and disadvantages of the different remediation strategies, as well as updates of the research progress of these strategies for AFB1, DON, ZEN and FB1 control in the feed industry.

Abstract Background The current study was conducted to investigate the individual and combined occurrence of aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEN) in feeds from various Provinces of China during 2018 to 2020. A total of 3,507 feed samples, including 2,090 feed ingredients and 1,417 complete feed samples, were collected from different areas of China for mycotoxins analysis. Results The individual contamination of AFB1, DON and ZEN were present in more than 81.9%, 96.4% and 96.9% of feed samples, respectively, with average concentration ranges of AFB1 between 1.2–27.4 μg/kg, DON between 458.0–1,925.4 μg/kg and ZEN between 48.1–326.8 μg/kg. Notably, 0.9%, 0.5% and 0.1% of feed ingredients, and 1.2–12.8%, 0.9–2.9% and 0–8.9% of complete feeds for pigs, poultry and ruminants with AFB1, ZEN and DON that exceeded China’s safety standards, respectively. Moreover, more than 81.5% of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins. Conclusion This study indicates that the feeds in China were universally contaminated with AFB1, DON and ZEN during the past 3 years. These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed, and the importance of carrying out feed administration and remediation strategies for mycotoxin control.

In the original publication [...]

Aflatoxin B1 (AFB1) is amongst the mycotoxins commonly affecting human and animal health, raising global food safety and control concerns. The mechanisms underlying AFB1 toxicity are poorly understood. Moreover, antidotes against AFB1 are lacking. Genome-wide CRISPR/Cas9 knockout screening in porcine kidney cells identified the transcription factor BTB and CNC homolog 1 (BACH1) as a gene required for AFB1 toxicity. The inhibition of BACH1 expression in porcine kidney cells and human hepatoma cells resulted in increased resistance to AFB1. BACH1 depletion attenuates AFB1-induced oxidative damage via the upregulation of antioxidant genes. Subsequently, virtual structural screening identified the small molecule 1-Piperazineethanol, α-[(1,3-benzodioxol-5-yloxy)methyl] -4-(2-methoxyphenyl) (M2) as an inhibitor of BACH1. M2 and its analogues inhibited AFB1-induced porcine and human cell death in vitro, while M2 administration significantly improved AFB1-induced symptoms of weight loss and liver injury in vivo. These findings demonstrate that BACH1 plays a central role in AFB1-induced oxidative damage by regulating antioxidant gene expression. We also present a potent candidate small-molecule inhibitor in developing novel treatments for AFB1 toxicity.

Aflatoxin is a known mycotoxin that pollutes various grains widely in the environment. Aflatoxin B1 (AFB1) and Aflatoxin M1 (AFM1) have been shown to induce cytotoxicity in many cells, yet their effects on mammary epithelial cells remain unclear. In this study, we examined the toxicity and the effects of AFB1 and AFM1 on bovine mammary epithelial cells (BME cells). The cells were treated with AFB1 or AFM1 at a concentration of 0–10 mg/L for 24 or 48 h, followed by cytotoxicity assays, flow cytometry, and transcriptomics. Our results demonstrated that AFB1 and AFM1 induced cell proliferation inhibition, apoptosis and cell cycle arrest. However, the level of intracellular reactive oxygen species has no significant difference. The RNA-Seq results also showed that AFB1 and AFM1 changed many related gene expressions like apoptosis and oxidative stress, cycle, junction, and signaling pathway. Taken together, AFB1 and AFM1 were found to affect cytotoxicity and related gene changes in BME cells. Notably, this study reported that 2 mg/L of AFB1 and AFM1 affected the expression of methylation-related genes, and ultimately altered the rate of m6A methylation in RNA. It may provide a potential direction for toxins to indirectly regulate gene expression by affecting RNA methylation modification. Our research provides some novel insights and data about AFB1 and AFM1 toxicity in BME cells.

Aflatoxin B1 (AFB1) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB1-induced immunotoxicity and oxidative stress via NF-κB and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control); 2. Basal diet + AFB1 1mg/kg contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB1 1 mg/kg + GSPE 250 mg/kg (AFB1 + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1β, IL-10, and IL-6 induced by AFB1. Similarly, GSPE + AFB1 treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the splenic tissue compared to the AFB1 treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of IκBα protein induced by AFB1. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB1 group. Taken together, GSPE alleviates AFB1-induced immunotoxicity and oxidative damage by inhibiting the NF-κB and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB1-induced immunotoxicity and oxidative damage.

Host defense peptides (HDPs) are efficient defense components of the innate immune system, playing critical roles in intestinal homeostasis and protection against pathogens. This study aims to investigate the interference effects of DON on the intestinal porcine HDPs expression in piglets and intestinal porcine epithelial cell line (IPEC-J2) cells, and elucidate the underlying mechanisms through which it functions. In an animal experiment, intestinal HDPs were determined in weaned piglets fed control and 1.28 mg/kg or 2.89 mg/kg DON-contaminated diets. Dietary exposure to DON significantly decreased piglet average daily gain, increased intestinal permeability and depressed the expression of porcine β-defensin1 (pBD1), pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C), PMAP23, and proline/arginine-rich peptide of 39 amino acids (PR39) in the intestine (p < 0.05). In IPEC-J2 cells, DON decreased cell viability and inhibited the expression of pBD1, pBD3, pEP2C, PG1-5, and PR39 (p < 0.05). NOD2, key regulator that is responsible for HDPs production, was markedly downregulated, whereas caspase-12 was activated in the presence of DON. In conclusion, DON induced caspase-12 activation and inhibited the NOD2-mediated HDPs production, which led to an impaired intestinal barrier integrity of weaned piglets. Our study provides a promising target for future therapeutic strategies to prevent the adverse effects of DON.

The authors wish to make the following correction to their paper [...]

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens.

Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0–21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3β-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females.

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens. [ABSTRACT FROM AUTHOR]

Seven combinations of monensin (33 mg/kg of the dietary DM) and vegetable oils (coconut oil, palm oil, soybean oil, sunflower oil, canola oil and linseed oil) (33 g/kg of the dietary DM) supplementations were tested to reduce in vitro enteric methane production in goats. Data showed that all treatments from supplementation of monensin and vegetable oils significantly reduced in vitro enteric methane production compared to control from 40.55-48.58%. In addition, total gas production also decreased from7.37-29.47% and number of protozoa decreased from 64.15-75.47% compared with the control. Supplementation of monensin and vegetable oils had no effect on rumen pH, microbial protein, in vitro dry matter digestibility (IVDMD) and in vitro organic matter digestibility (IVOMD), but had effect on ammonia concentration. Supplementation of monensin and vegetable oils effectively lowered total gas production, enteric methane production and number of protozoa in the rumen. However, the best supplementation was monensin-sunflower oil (MSf) which can reduce total gas production up to 29.47%, enteric methane production up to 48.58%, number of protozoa up to 75.47% compared to control (CD), without affecting the process of fermentation in the rumen. [ABSTRACT FROM AUTHOR]