Physiologically based kinetic (PBK) modeling as a new approach methodology (NAM) for predicting systemic levels of gut microbial metabolites
Toxicol Lett. 2024 Apr 27:S0378-4274(24)00085-7. doi: 10.1016/j.toxlet.2024.04.013. Online ahead of print.ABSTRACTThere is a clear need to develop new approach methodologies (NAMs) that combine in vitro and in silico testing to reduce and replace animal use in chemical risk assessment. Physiologically based kinetic (PBK) models are gaining popularity as NAMs in toxico/pharmacokinetics, but their coverage of complex metabolic pathways occurring in the gut are incomplete. Chemical modification of xenobiotics by the gut microbiome plays a critical role in the host response, for example, by prolonging exposure to harmful metab...
Source: Toxicology Letters - April 30, 2024 Category: Toxicology Authors: Maja Stevanoska Jacob Folz Karsten Beekmann Georg Aichinger Source Type: research
Physiologically based kinetic (PBK) modeling as a new approach methodology (NAM) for predicting systemic levels of gut microbial metabolites
Toxicol Lett. 2024 Apr 27:S0378-4274(24)00085-7. doi: 10.1016/j.toxlet.2024.04.013. Online ahead of print.ABSTRACTThere is a clear need to develop new approach methodologies (NAMs) that combine in vitro and in silico testing to reduce and replace animal use in chemical risk assessment. Physiologically based kinetic (PBK) models are gaining popularity as NAMs in toxico/pharmacokinetics, but their coverage of complex metabolic pathways occurring in the gut are incomplete. Chemical modification of xenobiotics by the gut microbiome plays a critical role in the host response, for example, by prolonging exposure to harmful metab...
Source: Toxicology Letters - April 30, 2024 Category: Toxicology Authors: Maja Stevanoska Jacob Folz Karsten Beekmann Georg Aichinger Source Type: research
Vertebrate Response to Microplastics, Nanoplastics and Co-exposed Contaminants: Assessing Accumulation, Toxicity, Behaviour, Physiology, and Molecular Changes
Toxicol Lett. 2024 Apr 25:S0378-4274(24)00064-X. doi: 10.1016/j.toxlet.2024.04.004. Online ahead of print.ABSTRACTPollution from microplastics (MPs) and nanoplastics (NPs) has gained significant public attention and has become a serious environmental problem worldwide. This review critically investigates MPs/NPs' ability to pass through biological barriers in vertebrate models and accumulate in various organs, including the brain. After accumulation, these particles can alter individuals' behaviour and exhibit toxic effects by inducing oxidative stress or eliciting an inflammatory response. One major concern is the possibi...
Source: Toxicology Letters - April 27, 2024 Category: Toxicology Authors: Manjyot Kaur Anju Sharma Pradeep Bhatnagar Source Type: research
Chloropicrin Ocular Injury: Biomarkers, Potential Mechanisms, and Treatments
Toxicol Lett. 2024 Apr 25:S0378-4274(24)00077-8. doi: 10.1016/j.toxlet.2024.04.006. Online ahead of print.ABSTRACTOcular tissue, especially the cornea, is overly sensitive to chemical exposures. The availability and adoption of chemical threat agent chloropicrin (CP) is growing in the United States as a pesticide and fumigant; thereby increasing the risk of its use in warfare, terrorist attacks and non-intentional exposure. Exposure to CP results in immediate ocular, respiratory, and dermal injury; however, we lack knowledge on its mechanism of toxicity as well of its breakdown products like chlorine and phosgene, and effe...
Source: Toxicology Letters - April 27, 2024 Category: Toxicology Authors: Ebenezar O M Okoyeocha Neera Tewari-Singh Source Type: research
Vertebrate Response to Microplastics, Nanoplastics and Co-exposed Contaminants: Assessing Accumulation, Toxicity, Behaviour, Physiology, and Molecular Changes
Toxicol Lett. 2024 Apr 25:S0378-4274(24)00064-X. doi: 10.1016/j.toxlet.2024.04.004. Online ahead of print.ABSTRACTPollution from microplastics (MPs) and nanoplastics (NPs) has gained significant public attention and has become a serious environmental problem worldwide. This review critically investigates MPs/NPs' ability to pass through biological barriers in vertebrate models and accumulate in various organs, including the brain. After accumulation, these particles can alter individuals' behaviour and exhibit toxic effects by inducing oxidative stress or eliciting an inflammatory response. One major concern is the possibi...
Source: Toxicology Letters - April 27, 2024 Category: Toxicology Authors: Manjyot Kaur Anju Sharma Pradeep Bhatnagar Source Type: research
Chloropicrin Ocular Injury: Biomarkers, Potential Mechanisms, and Treatments
Toxicol Lett. 2024 Apr 25:S0378-4274(24)00077-8. doi: 10.1016/j.toxlet.2024.04.006. Online ahead of print.ABSTRACTOcular tissue, especially the cornea, is overly sensitive to chemical exposures. The availability and adoption of chemical threat agent chloropicrin (CP) is growing in the United States as a pesticide and fumigant; thereby increasing the risk of its use in warfare, terrorist attacks and non-intentional exposure. Exposure to CP results in immediate ocular, respiratory, and dermal injury; however, we lack knowledge on its mechanism of toxicity as well of its breakdown products like chlorine and phosgene, and effe...
Source: Toxicology Letters - April 27, 2024 Category: Toxicology Authors: Ebenezar O M Okoyeocha Neera Tewari-Singh Source Type: research
Roles of AhR/CYP1s Signal Pathway Mediated ROS Production in Uremic Cardiomyopathy
CONCLUSION: This study provides evidence that the AhR/CYP1s pathway is activated in UCM rats, and this activation is correlated with the uremic toxin IS. In vitro studies indicate that IS can stimulate the AhR translocation in cardiomyocyte, triggering to the production of intracellular ROS via CYP1s. This process leads to prolonged oxidative stress stimulation and thus contributes to the progression of uremic toxin-mediated cardiomyopathy.PMID:38670245 | DOI:10.1016/j.toxlet.2024.04.005 (Source: Toxicology Letters)
Source: Toxicology Letters - April 26, 2024 Category: Toxicology Authors: Wei Lu Shi Cheng Jiarui Xu Zilong Xiao Yong Yu Qiwen Xie Yi Fang Ruizhen Chen Bo Shen Yeqing Xie Xiaoqiang Ding Source Type: research
Roles of AhR/CYP1s Signal Pathway Mediated ROS Production in Uremic Cardiomyopathy
CONCLUSION: This study provides evidence that the AhR/CYP1s pathway is activated in UCM rats, and this activation is correlated with the uremic toxin IS. In vitro studies indicate that IS can stimulate the AhR translocation in cardiomyocyte, triggering to the production of intracellular ROS via CYP1s. This process leads to prolonged oxidative stress stimulation and thus contributes to the progression of uremic toxin-mediated cardiomyopathy.PMID:38670245 | DOI:10.1016/j.toxlet.2024.04.005 (Source: Toxicology Letters)
Source: Toxicology Letters - April 26, 2024 Category: Toxicology Authors: Wei Lu Shi Cheng Jiarui Xu Zilong Xiao Yong Yu Qiwen Xie Yi Fang Ruizhen Chen Bo Shen Yeqing Xie Xiaoqiang Ding Source Type: research
Non-alcoholic fatty liver disease changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats
In conclusion, NALFD changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats, which may affect drug metabolism and pharmacokinetics. In clinical medication, drug monitoring should be strengthened to avoid potential risks.PMID:38663832 | DOI:10.1016/j.toxlet.2024.04.010 (Source: Toxicology Letters)
Source: Toxicology Letters - April 25, 2024 Category: Toxicology Authors: Yifei Shen Jie Liu Bingyi Yao Yuanjin Zhang Shengbo Huang Chenmeizi Liang Junze Huang Yu Tang Xin Wang Source Type: research
Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation
Toxicol Lett. 2024 Apr 18;396:19-27. doi: 10.1016/j.toxlet.2024.04.007. Online ahead of print.ABSTRACTRicin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstra...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Yuxin Xu Mingxin Dong Chengbiao Sun Yan Wang Na Zhao Kaikai Yu Nan Lu Na Xu Wensen Liu Congmei Wu Source Type: research
Inhibition kinetics of acetylcholinesterase and butyrylcholinesterase from various species by 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP)
Toxicol Lett. 2024 Apr 18;396:28-33. doi: 10.1016/j.toxlet.2024.04.003. Online ahead of print.ABSTRACTThe aerotoxic syndrome has been associated with exposure to tricresyl phosphate (TCP), which is used as additive in hydraulic fluids and engine lubricants. The toxic metabolite 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP) is formed from the TCP isomer tri-ortho-cresyl phosphate (TOCP) in vivo and is known to react with the active site serine in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) resulting in the inhibition of the enzymes. Previous in vitro studies showed pronounced species differences...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Gabriele Horn Sebastian Rappengl ück Franz Worek Source Type: research
Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation
Toxicol Lett. 2024 Apr 18;396:19-27. doi: 10.1016/j.toxlet.2024.04.007. Online ahead of print.ABSTRACTRicin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstra...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Yuxin Xu Mingxin Dong Chengbiao Sun Yan Wang Na Zhao Kaikai Yu Nan Lu Na Xu Wensen Liu Congmei Wu Source Type: research
Inhibition kinetics of acetylcholinesterase and butyrylcholinesterase from various species by 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP)
Toxicol Lett. 2024 Apr 18;396:28-33. doi: 10.1016/j.toxlet.2024.04.003. Online ahead of print.ABSTRACTThe aerotoxic syndrome has been associated with exposure to tricresyl phosphate (TCP), which is used as additive in hydraulic fluids and engine lubricants. The toxic metabolite 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP) is formed from the TCP isomer tri-ortho-cresyl phosphate (TOCP) in vivo and is known to react with the active site serine in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) resulting in the inhibition of the enzymes. Previous in vitro studies showed pronounced species differences...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Gabriele Horn Sebastian Rappengl ück Franz Worek Source Type: research
Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation
Toxicol Lett. 2024 Apr 18;396:19-27. doi: 10.1016/j.toxlet.2024.04.007. Online ahead of print.ABSTRACTRicin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstra...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Yuxin Xu Mingxin Dong Chengbiao Sun Yan Wang Na Zhao Kaikai Yu Nan Lu Na Xu Wensen Liu Congmei Wu Source Type: research
Inhibition kinetics of acetylcholinesterase and butyrylcholinesterase from various species by 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP)
Toxicol Lett. 2024 Apr 18;396:28-33. doi: 10.1016/j.toxlet.2024.04.003. Online ahead of print.ABSTRACTThe aerotoxic syndrome has been associated with exposure to tricresyl phosphate (TCP), which is used as additive in hydraulic fluids and engine lubricants. The toxic metabolite 2-(2-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide (CBDP) is formed from the TCP isomer tri-ortho-cresyl phosphate (TOCP) in vivo and is known to react with the active site serine in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) resulting in the inhibition of the enzymes. Previous in vitro studies showed pronounced species differences...
Source: Toxicology Letters - April 20, 2024 Category: Toxicology Authors: Gabriele Horn Sebastian Rappengl ück Franz Worek Source Type: research
