Elevated intracellular Ca < sup > 2+ < /sup > functions downstream of mitodysfunction to induce Wallerian-like degeneration and necroptosis in organophosphorus-induced delayed neuropathy
This study was designed to investigate that deregulated cytosolic Ca2+ may function downstream of mitodysfunction in activating Wallerian-like degeneration and necroptosis in OPIDN. Adult hens were administrated a single dosage of 750mg/kg tri-ortho-cresyl phosphate (TOCP), and then sacrificed at 1day, 5day, 10day and 21day post-exposure, respectively. Sciatic nerves and spinal cords were examined for pathological changes and proteins expression related to Wallerian-like degeneration and necroptosis. In vitro experiments using differentiated neuro-2a (N2a) cells were conducted to investigate the relationship among mitochon...
Source: Toxicology - April 23, 2024 Category: Toxicology Authors: Mingxue Song Kang Kang Shuai Wang Cuiqin Zhang Xiulan Zhao Fuyong Song Source Type: research

Lead exerts a depression of neurotransmitter release through a blockade of voltage dependent calcium channels in chromaffin cells
Toxicology. 2024 Apr 20:153809. doi: 10.1016/j.tox.2024.153809. Online ahead of print.ABSTRACTThe present work, using chromaffin cells of bovine adrenal medullae (BCCs), aims to describe what type of ionic current alterations induced by lead (Pb2+) underlies its effects reported on synaptic transmission. We observed that the acute application of Pb2+ lead to a drastic depression of neurotransmitters release in a concentration-dependent manner when the cells were stimulated with both K+ or acetylcholine, with an IC50 of 119,57 μM and of 5,19 μM, respectively. This effect was fully recovered after washout. Pb2+ also blocke...
Source: Toxicology - April 22, 2024 Category: Toxicology Authors: Victoria Jim énez Carretero Ninfa Liccardi Maria Arribas Tejedor Ricardo de Pascual Jorge Hern ández Campano Jes ús M Hernández-Guijo Source Type: research

Sex, Age, and Species Differences of Perfluorooctanoic Acid Modeled by Flow- versus Permeability-limited Physiologically-Based Pharmacokinetic Models
In conclusion, the permeability PBPK model could interpret age, sex, and species differences and it could improve the accuracy of human prediction.PMID:38642821 | DOI:10.1016/j.tox.2024.153806 (Source: Toxicology)
Source: Toxicology - April 20, 2024 Category: Toxicology Authors: Go-Wun Choi Dong Wook Kang Ju Hee Kim Seok-Jin Cho Yong-Bok Lee In-Ho Kwon Hea-Young Cho Source Type: research

Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells
This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information re...
Source: Toxicology - April 20, 2024 Category: Toxicology Authors: Linjing Xu Huan Liu Yifeng Rang Lizi Zhou Xukai Wang Yinhuan Li Chunhong Liu Source Type: research

Decabromodiphenyl Ether Exposure Reduces Dabrafenib Sensitivity of Papillary Thyroid Carcinoma Harboring BRAF < sup > V600E < /sup > mutation through the EGFR-CRAF-MAPK Pathway: An In Vitro Study
Toxicology. 2024 Apr 17:153807. doi: 10.1016/j.tox.2024.153807. Online ahead of print.ABSTRACTDecabromodiphenyl ether (BDE209) has been demonstrated to be associated with thyroid dysfunction and thyroid carcinoma risk as a widely used brominated flame retardants. Although dabrafenib has been confirmed to be a promising therapeutic agent for papillary thyroid carcinoma (PTC) harboring BRAFV600E mutation, the rapid acquired dabrafenib resistance has brought a great challenge to clinical improvement and the underpinning mechanisms remain poorly defined. By treating PTC-derived and normal follicular epithelial cell lines with ...
Source: Toxicology - April 19, 2024 Category: Toxicology Authors: Xinpei Wang Xiujie Cui Yi Wang Qianqian Wang Feifei Sun Zhiyan Liu Source Type: research

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats
The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced ...
Source: Toxicology - April 15, 2024 Category: Toxicology Authors: Jintao Wang Yuan Xue Bin Wu Ming Lei Honglei Ma Xinxing He Qi Tan Jian Guan Wei Song Renfu Li Xinguang Cui Source Type: research

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats
The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced ...
Source: Toxicology - April 15, 2024 Category: Toxicology Authors: Jintao Wang Yuan Xue Bin Wu Ming Lei Honglei Ma Xinxing He Qi Tan Jian Guan Wei Song Renfu Li Xinguang Cui Source Type: research

Toxic effect and mRNA mechanism of moon dust simulant induced pulmonary inflammation in rats
The objective of this study is to investigate the pattern and mechanism of lung inflammation induced by subacute exposure to moon dust simulants (MDS) in rats. SD rats were exposed to MDS and silica dioxide through oral and nasal inhalation for 6hours per day continuously for 15 days. Pathological analysis indicated that the toxicity of MDS was lower than that of silica dioxide. MDS led to a notable recruitment and infiltration of macrophages in the rat lungs. Material characterization and biochemical analysis revealed that SiO2, Fe2O3, and TiO2 could be crucial sources of MDS toxicity. The study revealed that MDS-induced ...
Source: Toxicology - April 15, 2024 Category: Toxicology Authors: Jintao Wang Yuan Xue Bin Wu Ming Lei Honglei Ma Xinxing He Qi Tan Jian Guan Wei Song Renfu Li Xinguang Cui Source Type: research

Nanomaterials-induced programmed cell death: Focus on mitochondria
Toxicology. 2024 Apr 12:153803. doi: 10.1016/j.tox.2024.153803. Online ahead of print.ABSTRACTNanomaterials are widely utilized in several domains, such as everyday life, societal manufacturing, and biomedical applications, which expand the potential for nanomaterials to penetrate biological barriers and interact with cells. Multiple studies have concentrated on the particular or improper utilization of nanomaterials, resulting in cellular death. The primary mode of cell death caused by nanotoxicity is programmable cell death, which includes apoptosis, ferroptosis, necroptosis, and pyroptosis. Based on our prior publicatio...
Source: Toxicology - April 14, 2024 Category: Toxicology Authors: Shijia Qiao Yiyuan Kang Xiner Tan Xinru Zhou Can Zhang Shulin Lai Jia Liu Longquan Shao Source Type: research

Nanomaterials-induced programmed cell death: Focus on mitochondria
Toxicology. 2024 Apr 12:153803. doi: 10.1016/j.tox.2024.153803. Online ahead of print.ABSTRACTNanomaterials are widely utilized in several domains, such as everyday life, societal manufacturing, and biomedical applications, which expand the potential for nanomaterials to penetrate biological barriers and interact with cells. Multiple studies have concentrated on the particular or improper utilization of nanomaterials, resulting in cellular death. The primary mode of cell death caused by nanotoxicity is programmable cell death, which includes apoptosis, ferroptosis, necroptosis, and pyroptosis. Based on our prior publicatio...
Source: Toxicology - April 14, 2024 Category: Toxicology Authors: Shijia Qiao Yiyuan Kang Xiner Tan Xinru Zhou Can Zhang Shulin Lai Jia Liu Longquan Shao Source Type: research

In Vitro Toxicological Evaluation of glo menthol and non-menthol Heated Tobacco Products
Toxicology. 2024 Apr 11:153801. doi: 10.1016/j.tox.2024.153801. Online ahead of print.ABSTRACTHeated tobacco products (HTPs) are non-combustible, inhaled tobacco products that generate an aerosol with fewer and lower levels of toxicants, with a potential to reduce risk relative to cigarette smoking. Here, we assessed in vitro toxicological effects of three menthol (glo neo neoCLICK, neo Smooth Menthol and Fresh Menthol) and one non-menthol (neo Smooth Tobacco) variants of glo HTP, along with market comparators for cigarettes and HTPs. Limited chemical characterization of the study products revealed significantly lower leve...
Source: Toxicology - April 13, 2024 Category: Toxicology Authors: Brian M Keyser Robert Leverette Reagan McRae John Wertman Tom Shutsky Kristen Jordan Ken Szeliga Patrudu Makena Source Type: research

The p21 < sup > + < /sup > perinecrotic hepatocytes produce the chemokine CXCL14 after a severe acetaminophen overdose promoting hepatocyte injury and delaying regeneration
Toxicology. 2024 Apr 12;504:153804. doi: 10.1016/j.tox.2024.153804. Online ahead of print.ABSTRACTFifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete ...
Source: Toxicology - April 13, 2024 Category: Toxicology Authors: David S Umbaugh Nga T Nguyen Sawyer H Smith Anup Ramachandran Hartmut Jaeschke Source Type: research

In Vitro Toxicological Evaluation of glo menthol and non-menthol Heated Tobacco Products
Toxicology. 2024 Apr 11:153801. doi: 10.1016/j.tox.2024.153801. Online ahead of print.ABSTRACTHeated tobacco products (HTPs) are non-combustible, inhaled tobacco products that generate an aerosol with fewer and lower levels of toxicants, with a potential to reduce risk relative to cigarette smoking. Here, we assessed in vitro toxicological effects of three menthol (glo neo neoCLICK, neo Smooth Menthol and Fresh Menthol) and one non-menthol (neo Smooth Tobacco) variants of glo HTP, along with market comparators for cigarettes and HTPs. Limited chemical characterization of the study products revealed significantly lower leve...
Source: Toxicology - April 13, 2024 Category: Toxicology Authors: Brian M Keyser Robert Leverette Reagan McRae John Wertman Tom Shutsky Kristen Jordan Ken Szeliga Patrudu Makena Source Type: research

The p21 < sup > + < /sup > Perinecrotic Hepatocytes Produce the Chemokine CXCL14 After a Severe Acetaminophen Overdose Promoting Hepatocyte Injury and Delaying Regeneration
Toxicology. 2024 Apr 11:153804. doi: 10.1016/j.tox.2024.153804. Online ahead of print.ABSTRACTFifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete popu...
Source: Toxicology - April 13, 2024 Category: Toxicology Authors: David S Umbaugh Nga T Nguyen Sawyer H Smith Anup Ramachandran Hartmut Jaeschke Source Type: research

The effects of micro- and nanoplastic on the central nervous system: A New Threat to Humanity?
This article aims to provide a comprehensive overview of the knowledge of MNPs and the potential mechanisms of their impact on the central nervous system. Numerous in vivo and in vitro studies have shown that exposure to MNPs may pass through the blood-brain barrier (BBB) and lead to neurotoxicity through impairments in oxidative and inflammatory balance, neurotransmitter alternation, nerve conduction-related key enzymes, and impact through the gut-brain axis. It is worth noting that MNPs may act as carriers and have more severe effects on the body when co-exposed with other substances. MNPs of smaller sizes cause more sev...
Source: Toxicology - April 12, 2024 Category: Toxicology Authors: Yanxu Zheng Shengchao Xu Jingyu Liu Zhixiong Liu Source Type: research