Environmental Toxicology最新文献

Flurochloridone (FLC) is a selective herbicide that can cause reproductive toxicity in male rats. However, limited information is available regarding the toxicity of FLC in the developmental stages of aquatic organisms. This study aimed to investigate the effects of FLC exposure during embryonic development and elucidate its potential mechanism of action. Zebrafish embryos were exposed to 6.25, 12.5, 25, and 50 μg/mL FLC for 4-144 hpf. The developmental status of embryos was recorded; the indicators of oxidative stress and embryonic apoptosis were determined. We found that FLC exposure caused severe embryonic malformations, such as pericardial edema, spinal curvature, and growth retardation, accompanied by a decreased hatching and survival rate. After exposure until 144 h postfertilization, the median lethal concentration (LC₅₀) of FLC in zebrafish embryos was 36.9 μg/mL. Subsequently, FLC induced the accumulation of reactive oxygen species and malondialdehyde, enhanced the activity of superoxide dismutase, and activated the Keap1-Nrf2 signaling pathway. Further studies confirmed that FLC can induce apoptosis in zebrafish embryos through the activation of caspase. These results suggest that FLC induced developmental toxicity in zebrafish embryos, which provides new evidence regarding FLC toxicity in aquatic organisms and to assess human health risks.

Numerous contemporary diseases are linked to food contamination. Pathogenic agents might stem from certain food ingredients or result from pollution stemming from food processing or packaging. One such contaminant is 3-Chloro-1,2-propanediol (3-MCPD), it has been previously reported to be produced during the preparation of chemical sauces, as well as during the heating of baked goods. Yet, uncertainty surrounds its potential to induce embryonic developmental toxicity. In this study, zebrafish were employed as the focal point to assess the impact of 3-MCPD on initial embryonic development, heart functionality, and behavior. The research unveiled that exposure of zebrafish embryos to 18, 36, and 54 mM 3-MCPD led to cardiac anomalies, including pericardial edema, reduced heart rate, and elongated SV-BA distance. Additionally, 3-MCPD exposure triggered aberrations in cardiac-related gene expression and an elevation in oxidative stress. Notably, behavioral changes were observed in 3-MCPD-exposed zebrafish embryos, while vascular development appeared unaffected. This study introduces a novel basis for comprehensive exploration of 3-MCPD toxicity.

Fluoride (F^-) is a major groundwater contaminant spread across the world. In excess concentrations, F^- can be detrimental to living beings. F^- exposure is linked to cellular redox dyshomeostasis, leading to oxidative stress-mediated pathologies including heart dysfunction. Due to its potent antioxidant properties, various phytochemicals are found to alleviate the symptoms of F^- toxicity. Hence, we explore the protective effect of esculin (Esc), a coumarin glucoside on F^--induced oxidative stress and cardiotoxicity in zebrafish larvae. The experimental groups consisted of NaF (50 ppm) and Esc (100 μM) groups treated alone and in combination with a control group for 6 h. The groups were maintained till 78 hpf after which the level of oxidants (ROS, LPO, and PCC) and antioxidants (GST, GSH, GPx, SOD, and CAT) were assessed. The results revealed that Esc pretreatment restored the depleted antioxidant markers and reduced the levels of oxidant in the Esc+NaF group, exhibiting its antioxidant potential. In addition, analyses of the heartbeat rate and hemoglobin integrity using o-Dianisidine staining were conducted in the control and experimental groups. Esc treatment prevents F^- induced cardiac changes including tachycardia and altered blood flow. Further, the mRNA expression level of antioxidant genes (nrf2, gstp1, hmox1a, prdx1, and nqo1) and cardiac developmental genes (bmp2b, nkx2.5, myh6, and myl7) confirmed that Esc acts as a potent free radical scavenger and antioxidant defense enhancer, protecting zebrafish larvae from NaF-induced oxidative stress and heart dysfunction.

The glutamatergic signaling pathway, which is mediated by N-methyl-D-aspartate (NMDA) receptors, is crucial for osteoblast differentiation and bone function. Dextromethorphan (DXM), a widely used antitussive, is a noncompetitive antagonist of the NMDA receptor. However, the effects of DXM on osteoblast and bone regeneration remain unclear. The present study investigated the effects of DXM on osteogenesis in vitro and in vivo. A MC3T3-E1 preosteoblast cell line was treated with varying concentrations of DXM. Real-time-quantitative polymerase chain reaction (RT-qPCR) and Western-blot analysis were performed to evaluate the expression of osteogenesis-related runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), collagen type 1α (Col-1α), and alkaline phosphatase (ALP) after DXM treatment. Zebrafish embryos were incubated with DXM, which had potential to affect the ossification of the vertebrae and skull, and analyzed using calcein staining. Furthermore, we used a rat calvarial defect model to assess the effects of DXM on bone regeneration by using microcomputed tomography. The results indicate that DXM inhibited extracellular mineralization, ALP activity, and the expression of osteogenic markers, namely RUNX2, OSX, OCN, Col-1α, and ALP, in MC3T3-E1 cells. DXM suppressed skeleton ossification in zebrafish and affected bone regeneration in rats with calvarial defects. However, the mineral density of the regenerated bones did not differ significantly between the DXM and control groups. The present study demonstrated that DXM negatively affects the osteogenic function of osteoblasts, leading to impaired skeletal development and bone regeneration. Thus, clinicians should consider the negative effects of DXM on bone regeneration.

As a conventional immunosuppressive drug, cyclophosphamide (CYP) exhibits strong hepatotoxicity in clinical applications. Betulinic acid (BA) is a natural triterpenoid that protects against liver damage. However, the underlying mechanism has not yet been elucidated. The purpose of this study was to evaluate the ameliorative effects of BA on CYP-induced hepatotoxicity and further clarify the underlying mechanism. BA pretreatment mitigated CYP-induced liver oxidative damage by alleviating histopathological lesions, reducing reactive oxygen species (ROS) accumulation, and restoring the mRNA expression of antioxidant enzymes (Cu-Sod, Mn-Sod, Cat, and Gsh-Px). BA treatment also suppressed CYP-induced oxidative stress by activating the NRF2 pathway and inhibiting the MAPK signaling pathway. Moreover, BA attenuated CYP-triggered hepatic apoptosis by suppressing excessive mitochondrial fission, boosting mitochondrial fusion, and ameliorating pro-apoptotic protein expression (CASP9 and the ratio of BCL-2/BAX) by blocking the oxidative stress-activated mitochondrial apoptotic pathway. Furthermore, PD98059 (an inhibitor of ERK) and/or BA abated CYP-provoked hepatotoxicity by inhibiting the ERK-MAPK and mitochondrial apoptotic pathways, implying that deactivation of the ERK-mediated mitochondrial apoptotic pathway contributed to the hepatoprotective efficacy of BA against CYP-induced oxidative stress. Therefore, BA could be used as a complementary medicine in patients undergoing CYP treatment owing to its hepatoprotective effects.

Bladder cancer is one of the most common human malignancies worldwide. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is crucial to driving malignant progression and predicting poor prognosis of multiple human cancers, including bladder cancer, making STAT3 a promising target of cancer therapeutics. Cryptotanshinone (CTS) is an anticancer ingredient of Danshen (Salvia miltiorrhiza), a top-graded Chinese medicinal herb. However, whether CTS targets STAT3 to exert its cytotoxic effect on human bladder cancer remains unknown. Herein, we demonstrated that CTS is cytotoxic to multiple human urinary bladder transitional cell carcinoma (TCC) cell lines while sparing normal human urothelial cells. CTS provoked apoptosis-dependent bladder TCC cytotoxicity, as apoptosis blockage by z-VAD-fmk markedly rescued the clonogenicity of CTS-treated cells. Besides, CTS was found to suppress constitutive and interleukin 6-inducible activation of STAT3, evidenced by the downregulation of STAT3 tyrosine 705 phosphorylation and BCL2, a recognized STAT3 transcriptional target. Notably, ectopic expression of a dominant-active STAT3 mutant (STAT3-C) or BCL-2 alleviated CTS-induced apoptosis and clonogenicity inhibition, thus confirming STAT3 blockade as a pivotal mechanism of CTS's cytotoxic action on bladder TCC cells. Lastly, immunoblotting revealed that CTS lowered the levels of active JAK2, an upstream kinase that mediates STAT3 tyrosine 705 phosphorylation. Altogether, we conclude that the blockade of the JAK2/STAT3/BCL-2 antiapoptotic signaling axis is a vital mechanism whereby CTS provokes bladder cancer cytotoxicity. The current evidence implicates CTS's potential to be translated into a bladder cancer therapeutic agent.

Spiromesifen (SPM) is widely used for orchard mites and white fly control. The ecotoxicological data suggested that SPM is highly toxic to fish, but the information about its toxic effect on zebrafish is still obscure. In this study, adult zebrafish were exposed to SPM for 21 days. The plasma sex steroid hormone levels reflected the ratio of 17β-estradiol (E2) to testosterone (T) (E2/T) was significantly increased at 0.50 μg/L of SPM in male fish (2.4-fold, p = 0.049). Following 21 days' post exposure, distinct pathological changes were noted in gonad, males were more sensitive than female, which showed the interstitial connective tissue hyperplasia and widener in testis at 15 μg/L of SPM. In male fish, the relative percentage of spermatozoa was 13% decreased at 30 μg/L of SPM (p = 0.041). Which suggest SPM potential role in disrupting male gonad development. qRT-PCR results suggest that expression of follicle stimulating hormone receptor (fshr) was significantly down regulated in female zebrafish (0.29 fold of control, p = 0.010). Variable importance of projection (VIP) scores indicate the most important features separate in female and male. The different response of steroid level towards SPM between male and female zebrafish may due to the distinct regulation of key genes related in steroidogenesis and metabolism. This study for the first time connects the biochemical and histological to reveal the adverse effects of SPM on adult zebrafish in a sex dependent manner.

Retraction: H. Xu, N. Yang, B.Y. Wang, L. Zhou, L.L. Xu, Y. Chen, D.J. Wang, and W.H. Ge, "Phenylacetyl Glutamine (PAGln) Enhances Cardiomyocyte Death after Myocardial Infarction through β1 Adrenergic Receptor," Environmental Toxicology 39, no. 3 (2024): 1682-1699, https://doi.org/10.1002/tox.24063. The above article, published online on 02 December 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Paul B. Tchounwou; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. In addition, the investigation found there was significant unattributed textual overlap between this article and a previously-published article (Beale et al., 2008; https://doi.org/10.1186/1471-2407-8-200). Therefore, the article must be retracted. The authors Weihong Ge and Hang Xu disagree with this decision. The other authors did not respond.