The Mechanism of Blood Coagulation Induced by Sodium Dehydroacetate via the Regulation of the mTOR/ERK Pathway in Rats
Toxicol Lett. 2023 Dec 14:S0378-4274(23)01117-7. doi: 10.1016/j.toxlet.2023.12.009. Online ahead of print.ABSTRACTDehydroacetic acid (DHA-S), a potent antifungal and antibacterial agent, is widely used in food, feed and cosmetics. However, recent studies have shown that DHA-S could pose a risk for human and animal health. We had previously reported that DHA-S could cause coagulation disorders in rats and chicken. In the present study, we further confirmed that DHA-S induced blood coagulation via VKORC1 and VKORC1L1 in rats, and elucidated the role played by mTOR/ERK signaling. The in vivo studies demonstrated that PT, APTT...
Source: Toxicology Letters - December 16, 2023 Category: Toxicology Authors: Meng Zhang Qingqi Zhang Weiya Zhao Xin Chen Yumei Zhang Source Type: research

The association between neuropsychiatric effects of substance use and occurrence of endoplasmic reticulum and unfolded protein response: A systematic review
CONCLUSIONS: The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.PMID:38101493 | DOI:10.1016/j.toxlet.2023.12.008 (Source: Toxicology Letters)
Source: Toxicology Letters - December 15, 2023 Category: Toxicology Authors: Bin Yang Ruiling Zhang Mohammad Farris Iman Leong Bin Abdullah Source Type: research

Gentamicin administration leads to synaptic dysfunction in inner hair cells
In this study, we intraperitoneally injected C57BL/6J mice with 300mg/kg gentamicin once daily for 3, 10, and 20 days. Then, we performed immunofluorescence staining, patch-clamp recording, proteomics analysis and western blotting to characterize the changes in ribbon synapses in IHCs and the associated mechanisms. After gentamicin treatment, the auditory brainstem response (ABR) threshold was elevated, and the ABR wave I amplitude was decreased. We also observed loss of ribbon synapses in IHCs. Interestingly, ribbon synapse loss occurred on both the modiolar and pillar sides of IHCs. Whole-cell patch-clamp recordings in I...
Source: Toxicology Letters - December 15, 2023 Category: Toxicology Authors: Gen Li Yunge Gao Hao Wu Ting Zhao Source Type: research

The association between neuropsychiatric effects of substance use and occurrence of endoplasmic reticulum and unfolded protein response: A systematic review
CONCLUSIONS: The neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.PMID:38101493 | DOI:10.1016/j.toxlet.2023.12.008 (Source: Toxicology Letters)
Source: Toxicology Letters - December 15, 2023 Category: Toxicology Authors: Bin Yang Ruiling Zhang Mohammad Farris Iman Leong Bin Abdullah Source Type: research

Gentamicin administration leads to synaptic dysfunction in inner hair cells
In this study, we intraperitoneally injected C57BL/6J mice with 300mg/kg gentamicin once daily for 3, 10, and 20 days. Then, we performed immunofluorescence staining, patch-clamp recording, proteomics analysis and western blotting to characterize the changes in ribbon synapses in IHCs and the associated mechanisms. After gentamicin treatment, the auditory brainstem response (ABR) threshold was elevated, and the ABR wave I amplitude was decreased. We also observed loss of ribbon synapses in IHCs. Interestingly, ribbon synapse loss occurred on both the modiolar and pillar sides of IHCs. Whole-cell patch-clamp recordings in I...
Source: Toxicology Letters - December 15, 2023 Category: Toxicology Authors: Gen Li Yunge Gao Hao Wu Ting Zhao Source Type: research

An in-silico porcine model of phosgene-induced lung injury predicts clinically relevant benefits from application of continuous positive airway pressure up to 8  h post exposure
We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive air...
Source: Toxicology Letters - December 13, 2023 Category: Toxicology Authors: Sonal Mistry Timothy E Scott Bronwen Jugg Rosi Perrott Sina Saffaran Declan G Bates Source Type: research

Multi-Fusarium mycotoxin exposure activates Nrf2 and Ahr pathway in the liver of laying hens
This study investigates gene expression changes in laying hens exposed to trichothecene mycotoxins, known to induce oxidative stress and affect xenobiotic transformation and antioxidants. A 3-day feeding trial tested low and high doses of T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 in hen feed. Results showed increased expression of AHR, AHRR, HSP90, and CYP1A2 genes on days 2 and 3, suggesting a response to mycotoxin exposure. High doses down-regulated CYP1A2, AHR, and AHRR on day 1. KEAP1 expression decreased on day 1 but increased dose-dependently on days 2 and 3. NRF2 was up-regulated by low and down-regulated by hig...
Source: Toxicology Letters - December 13, 2023 Category: Toxicology Authors: Benjamin K övesi Szabina Kulcs ár Zsolt Ancsin M árta Erdélyi Erika Z ándoki Patrik G ömbös Kriszti án Balogh Mikl ós Mézes Source Type: research

An in-silico porcine model of phosgene-induced lung injury predicts clinically relevant benefits from application of continuous positive airway pressure up to 8  h post exposure
We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive air...
Source: Toxicology Letters - December 13, 2023 Category: Toxicology Authors: Sonal Mistry Timothy E Scott Bronwen Jugg Rosi Perrott Sina Saffaran Declan G Bates Source Type: research

Multi-Fusarium mycotoxin exposure activates Nrf2 and Ahr pathway in the liver of laying hens
This study investigates gene expression changes in laying hens exposed to trichothecene mycotoxins, known to induce oxidative stress and affect xenobiotic transformation and antioxidants. A 3-day feeding trial tested low and high doses of T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 in hen feed. Results showed increased expression of AHR, AHRR, HSP90, and CYP1A2 genes on days 2 and 3, suggesting a response to mycotoxin exposure. High doses down-regulated CYP1A2, AHR, and AHRR on day 1. KEAP1 expression decreased on day 1 but increased dose-dependently on days 2 and 3. NRF2 was up-regulated by low and down-regulated by hig...
Source: Toxicology Letters - December 13, 2023 Category: Toxicology Authors: Benjamin K övesi Szabina Kulcs ár Zsolt Ancsin M árta Erdélyi Erika Z ándoki Patrik G ömbös Kriszti án Balogh Mikl ós Mézes Source Type: research

Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
Toxicol Lett. 2023 Dec 7;391:39-44. doi: 10.1016/j.toxlet.2023.12.004. Online ahead of print.ABSTRACTCyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure with all-tr...
Source: Toxicology Letters - December 9, 2023 Category: Toxicology Authors: Barbara Kubickova Sarka Martinkova Dasa Bohaciakova Klara Hilscherova Source Type: research

Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
Toxicol Lett. 2023 Dec 7:S0378-4274(23)01111-6. doi: 10.1016/j.toxlet.2023.12.004. Online ahead of print.ABSTRACTCyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure...
Source: Toxicology Letters - December 9, 2023 Category: Toxicology Authors: Barbara Kubickova Šárka Martinková D áša Bohaciaková Kl ára Hilscherová Source Type: research

Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
Toxicol Lett. 2023 Dec 7:S0378-4274(23)01111-6. doi: 10.1016/j.toxlet.2023.12.004. Online ahead of print.ABSTRACTCyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure...
Source: Toxicology Letters - December 9, 2023 Category: Toxicology Authors: Barbara Kubickova Šárka Martinková D áša Bohaciaková Kl ára Hilscherová Source Type: research

Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid
Toxicol Lett. 2023 Dec 7:S0378-4274(23)01111-6. doi: 10.1016/j.toxlet.2023.12.004. Online ahead of print.ABSTRACTCyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure...
Source: Toxicology Letters - December 9, 2023 Category: Toxicology Authors: Barbara Kubickova Šárka Martinková D áša Bohaciaková Kl ára Hilscherová Source Type: research

Lipid characteristics of lung tissue in silicosis rat model were studied based on lipid metabolomics
Toxicol Lett. 2023 Dec 5:S0378-4274(23)01108-6. doi: 10.1016/j.toxlet.2023.12.002. Online ahead of print.ABSTRACTSilicosis is a common occupational disease caused by the long-term inhalation of large amounts of silica dust. Lipid metabolism plays an important role in the progression of silicosis, but its contributing mechanism remains unclear. The aim of this study was to investigate the differential lipid metabolites and active metabolic pathways in silicosis rat lung tissue. We first constructed a silicosis rat model, and randomly divided 24 male SD rats into control group (C), silicosis group for 1 week (S1W), silicosis...
Source: Toxicology Letters - December 7, 2023 Category: Toxicology Authors: Hailan He Rong Qi Jie Cui Mingming Liu Bo Guan Yufan Zhou Yingshu Zhang Xiaohui Hao Hongli Wang Heliang Liu Source Type: research

Pb induces the release of CXCL10 and CCL2 chemokines via mtROS/NF- κB activation in BV-2 cells
Toxicol Lett. 2023 Dec 5:S0378-4274(23)01110-4. doi: 10.1016/j.toxlet.2023.12.001. Online ahead of print.ABSTRACTLead (Pb), a well-known environmental pollutant, could cause damage of microglia, the resident macrophages vitally regulating inflammation in brain. Previous studies have found that Pb exposure induces typical pro-inflammatory factors release, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), but what effects of Pb treatment below the dose causing these factors release are unknown. Thus, cytokines assay was performed to identify the factors released from Pb-treated BV-2 cells at 2.5μM, cau...
Source: Toxicology Letters - December 7, 2023 Category: Toxicology Authors: Chenghao Jiang Xintong Li Cui Xiang Fang Ye Source Type: research