RESUMEN
Tricresyl phosphate (TCP) has received extensive attentions due to its potential adverse effects, while the toxicological information of TCP isomers is limited. In this study, 2 h post-fertilization zebrafish embryos were exposed to tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) or tri-p-cresyl phosphate (TpCP) at concentrations of 0, 100, 300 and 600 µg/L until 120 hpf, and the cardiotoxicity and mechanism of TCP isomers in zebrafish embryos/larvae were evaluated. The results showed that ToCP or TmCP exposure induced cardiac morphological defects and dysfunction in zebrafish, characterized by increased distance between sinus venosus and bulbus arteriosis, increased atrium and pericardial sac area, trabecular defects, and decreased heart rate and blood flow velocity, while no adverse effects of TpCP on zebrafish heart were found. Transcriptomic results revealed that extracellular matrix (ECM) and motor proteins, as well as PPAR signaling pathways, were included in the cardiac morphological defects and dysfunction induced by ToCP and TmCP. Co-exposure test with D-mannitol indicated that the inhibition of energy metabolism by ToCP and TmCP affected cardiac morphology and function by decreasing osmoregulation. This study is the first to report the cardiotoxicity induced by TCP in zebrafish from an isomer perspective, providing a new insight into the toxicity of TCP isomers and highlighting the importance of evaluating the toxicity of different isomers.
Asunto(s)
Cardiotoxicidad , Embrión no Mamífero , Pez Cebra , Animales , Pez Cebra/embriología , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/anomalías , Cardiotoxicidad/etiología , Larva/efectos de los fármacos , Corazón/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Tritolilfosfatos/toxicidadRESUMEN
Recently, we found that Ustiloxin A (UA, a mycotoxin) was widely detected in paddy environment and rice samples from several countries, and was also detected in human urine samples from China. However, the current knowledge about the health risks of UA are limited. In this research, the cytotoxicity of UA in mice renal tubular epithelial cells (mRTECs) was evaluated, and the results indicated that UA arrested cell cycle in G2/M phase via altering cellular morphology and microtubule, and inhibited the proliferation and division of mRTECs. Furthermore, UA could inhibit mitochondrial respiration via binding to the CoQ-binding site in dihydro-orotate dehydrogenase (DHODH) protein, and resulted in mitochondrial damage. These adverse effects of UA on mitochondria might be responsible for the cytotoxicity observed in vitro. In vivo, UA at concentrations that were comparable to the realistic concentrations of human exposure induced renal insufficiency in mice, and this might be associated with the renal mitochondrial damage in mice. However, exposure to UA at those realistic concentrations did not promote the progression from renal insufficiency to renal fibrosis and chronic kidney disease was not observed in mice.
Asunto(s)
Riñón , Insuficiencia Renal Crónica , Ratones , Humanos , Animales , Riñón/metabolismo , Células Epiteliales/metabolismo , Respiración , Mitocondrias/metabolismo , Proliferación CelularRESUMEN
Ustiloxin A (UA) and ustiloxin B (UB), two major mycotoxins produced by the pathogen of rice false smut (RFS) during rice cultivation, have attracted increasing attentions due to their potential health risks. However, limited data are available about their occurrence and fate in paddy fields and contamination profiles in rice. In this study, a field study was performed to investigate the occurrence and translocation of UA and UB in RFS-occurred paddies. For the first time to our knowledge, we reported a ubiquitous occurrence of the two ustiloxins in the paddy water (range: 0.01-3.46 µg/L for UA and <0.02-1.15 µg/L for UB) and brown rice (range: 0.09-154.08 µg/kg for UA and <0.09-23.57 µg/kg for UB). A significant positive correlation was observed between ustiloxin levels in paddy water and brown rice (rs = 0.48-0.79, p < 0.01). The occurrence of ustiloxin uptake in water-rice system was also evidenced by the rice exposure experiment, suggesting paddy water might be an important source for ustiloxin accumulation in rice. These results suggested that the contamination of ustiloxins in rice might occur widely, which was supported by the significantly high detection frequencies of UA (96.6%) and UB (62.4%) in polished rice (149 samples) from Hubei Province, China. The total concentrations of ustiloxins in the polished rice samples collected from Hubei Province ranged from <20.7 ng/kg (LOD) to 55.1 µg/kg (dry weight). Further studies are needed to evaluate the potential risks of ustiloxin exposure in the environment and humans.
Asunto(s)
Micotoxinas , Oryza , China , Humanos , AguaRESUMEN
Ustiloxins, a group of bioactive metabolites produced by the pathogen of rice false smut (RFS), have emerged as ubiquitous contaminants in RFS-occurred paddy fields and could accumulate in rice. Nevertheless, the prevalence of ustiloxins in rice and exposure risks of humans are limited. In this study, concentrations of ustiloxin A (UA) and ustiloxins B (UB), which are two predominant ustiloxins, were measured in 240 rice samples from China and 72 rice samples from 12 other counties. The detection rates (DRs) of UA and UB were 82.1% and 49.3%, respectively, and their concentrations in rice ranged from below detection limit (LOD: 0.22 µg/kg) to 85.96 µg/kg dw. Furthermore, for the first time, we reported the occurrence of UA (DR = 22.8%) in urine collected from residues of Enshi city, China. Urinary UA were significantly correlated with the activities of alanine aminotransferase in male, and this male-biased hepatotoxicity was further confirmed in mice exposure experiment. This study for the first time reported the widespread geographical distribution of ustiloxins in rice, as well as emphasized the occurrence of internal exposure and potential health risk in humans.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Oryza , Animales , China/epidemiología , Masculino , Ratones , Oryza/químicaRESUMEN
Due to global outbreak of rice false smut disease, ustiloxin A (UA) was detected in rice. However, accurate methods for monitoring UA in human body fluids were lacking. In this context, a UPLC-MS/MS method based on two-step SPE was constructed for measuring UA in urine. The limits of UA quantification in human and mice urine were 58.3 and 108.7 ng/L, respectively. The proposed method was applied to detect UA in urine samples collected from human and mice. After dietary exposure, the contents of UA in mice urine were from 6.03 to 16.76 µg/g of creatine, accounting for approximate 14% of daily intake dose. Furthermore, due to the trace residues in rice (78-109 ng/kg), no detectable UA was observed in the urine of 20 volunteers. To the best of our knowledge, it is the first time to report the occurrence of UA in mammal urine.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Péptidos Cíclicos/orina , Espectrometría de Masas en Tándem/métodos , Animales , Monitoreo Biológico , Femenino , Humanos , Límite de Detección , Modelos Lineales , Masculino , Ratones , Reproducibilidad de los Resultados , Extracción en Fase SólidaRESUMEN
Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) has commonly been used as an additive flame retardant and frequently detected in the aquatic environment and in biological samples worldwide. Recently, it was found that exposure to TDCIPP inhibited the growth of zebrafish, but the relevant molecular mechanisms remained unclear. In this study, 5 day-old crucian carp (Carassius auratus) larvae were treated with 0.5, 5, or 50 µg/L TDCIPP for 90 days; the effect on growth was evaluated; and related molecular mechanisms were explored. Results demonstrated that 5 or 50 µg/L TDCIPP treatment significantly inhibited the growth of crucian carp and downregulated the expression of growth hormones (ghs), growth hormone receptor (ghr), and insulin-like growth factor 1 (igf1). Molecular docking, dual-luciferase reporter gene assay, and in vitro experiments demonstrated that TDCIPP could bind to the growth hormone releasing hormone receptor protein of crucian carp and disturb the stimulation of growth hormone releasing hormone to the expression of ghs, resulting in the decrease of the mRNA level of gh1 and gh2 in pituitary cells. Our findings provide new perceptions into the molecular mechanisms of developmental toxicity of TDCIPP in fish.