Sulforaphane inhibits the migration and invasion of BPDE-induced lung adenocarcinoma cells by regulating NLRP12
This study aims to explore the impact and underlying mechanism of sulforaphane (SFN) intervention on the migration and invasion of lung adenocarcinoma induced by 7, 8-dihydroxy-9, 10-epoxy-benzo (a) pyrene (BPDE). Human lung adenocarcinoma A549 cells were exposed to varying concentrations of BPDE (0.25, 0.50, and 1.00 μM) and subsequently treated with 5 μM SFN. Cell viability was determined using CCK8 assay, while migration and invasion were assessed using Transwell assays. Lentivirus transfection was employed to establish NLRP12 overexpressing A549 cells. ELISA was utilized to quantify IL-33, CXCL12, and CXCL13 levels i...
Source: Toxicology and Applied Pharmacology - March 27, 2024 Category: Toxicology Authors: Wei Wang Shufan Chang Xi He XiaoLei Zhou Pingping Shang Yusong Chen Xiaoke Wang Lijuan Chen Qiao Zhang Yahong Qiao Feifei Feng Source Type: research

NDRG2 acts as a negative regulator of the progression of small-cell lung cancer through the modulation of the PTEN-AKT-mTOR signalling cascade
In conclusion, NDRG2 serves as an inhibitor of SCLC, and its cancer-inhibiting effects are achieved through the suppression of AKT/mTOR via the activation of PTEN. This work suggests that NDRG2 is a potential druggable target for SCLC treatment.PMID:38537875 | DOI:10.1016/j.taap.2024.116915 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - March 27, 2024 Category: Toxicology Authors: Zhenchuan Ma Yuefeng Ma Jie Feng Zhengshui Xu Chuantao Cheng Jie Qin Shaomin Li Jiantao Jiang Ranran Kong Source Type: research

The ABCB1 and ABCG2 efflux transporters limit brain disposition of the SYK inhibitors entospletinib and lanraplenib
Toxicol Appl Pharmacol. 2024 Mar 23:116911. doi: 10.1016/j.taap.2024.116911. Online ahead of print.ABSTRACTThe highly selective Spleen Tyrosine Kinase (SYK) inhibitors entospletinib and lanraplenib disrupt kinase activity and inhibit immune cell functions. They are developed for treatment of B-cell malignancies and autoimmunity diseases. The impact of P-gp/ABCB1 and BCRP/ABCG2 efflux transporters, OATP1a/1b uptake transporters and CYP3A drug-metabolizing enzymes on the oral pharmacokinetics of these drugs was assessed using mouse models. Entospletinib and lanraplenib were orally administered simultaneously at moderate dosa...
Source: Toxicology and Applied Pharmacology - March 25, 2024 Category: Toxicology Authors: Nancy H C Loos Rolf W Sparidans Paniz Heydari Vi ët Bui Maria C Lebre Jos H Beijnen Alfred H Schinkel Source Type: research

The ABCB1 and ABCG2 efflux transporters limit brain disposition of the SYK inhibitors entospletinib and lanraplenib
Toxicol Appl Pharmacol. 2024 Mar 23:116911. doi: 10.1016/j.taap.2024.116911. Online ahead of print.ABSTRACTThe highly selective Spleen Tyrosine Kinase (SYK) inhibitors entospletinib and lanraplenib disrupt kinase activity and inhibit immune cell functions. They are developed for treatment of B-cell malignancies and autoimmunity diseases. The impact of P-gp/ABCB1 and BCRP/ABCG2 efflux transporters, OATP1a/1b uptake transporters and CYP3A drug-metabolizing enzymes on the oral pharmacokinetics of these drugs was assessed using mouse models. Entospletinib and lanraplenib were orally administered simultaneously at moderate dosa...
Source: Toxicology and Applied Pharmacology - March 25, 2024 Category: Toxicology Authors: Nancy H C Loos Rolf W Sparidans Paniz Heydari Vi ët Bui Maria C Lebre Jos H Beijnen Alfred H Schinkel Source Type: research

Redox-activity and in vitro effects of regional atmospheric aerosol pollution: Seasonal differences and correlation between oxidative potential and in vitro toxicity of PM < sub > 1 < /sub >
Toxicol Appl Pharmacol. 2024 Mar 24;485:116913. doi: 10.1016/j.taap.2024.116913. Online ahead of print.ABSTRACTParticulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated. PM deposition in the lungs induces oxi...
Source: Toxicology and Applied Pharmacology - March 24, 2024 Category: Toxicology Authors: Gloria Melzi Lorenzo Massimi Maria Agostina Frezzini Martina Iulini Naima Tarallo Matteo Rinaldi Marco Paglione Emma Nozza Federica Crova Sara Valentini Gianluigi Valli Francesca Costabile Silvia Canepari Stefano Decesari Roberta Vecchi Marina Marinovich Source Type: research

MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation
This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone a...
Source: Toxicology and Applied Pharmacology - March 24, 2024 Category: Toxicology Authors: Li Tao Yu-Feng Xue Fei-Fei Sun Xue He Hong-Qian Wang Cheng-Cheng Tong Cheng Zhang De-Xiang Xu Xi Chen Source Type: research

Redox-activity and in vitro effects of regional atmospheric aerosol pollution: Seasonal differences and correlation between oxidative potential and in vitro toxicity of PM < sub > 1 < /sub >
Toxicol Appl Pharmacol. 2024 Mar 22:116913. doi: 10.1016/j.taap.2024.116913. Online ahead of print.ABSTRACTParticulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated. PM deposition in the lungs induces oxidati...
Source: Toxicology and Applied Pharmacology - March 24, 2024 Category: Toxicology Authors: Gloria Melzi Lorenzo Massimi Maria Agostina Frezzini Martina Iulini Naima Tarallo Matteo Rinaldi Marco Paglione Emma Nozza Federica Crova Sara Valentini Gianluigi Valli Francesca Costabile Silvia Canepari Stefano Decesari Roberta Vecchi Marina Marinovich Source Type: research

MitoQ protects against carbon tetrachloride-induced hepatocyte ferroptosis and acute liver injury by suppressing mtROS-mediated ACSL4 upregulation
This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone a...
Source: Toxicology and Applied Pharmacology - March 24, 2024 Category: Toxicology Authors: Li Tao Yu-Feng Xue Fei-Fei Sun Xue He Hong-Qian Wang Cheng-Cheng Tong Cheng Zhang De-Xiang Xu Xi Chen Source Type: research

TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome
Toxicol Appl Pharmacol. 2024 Mar 21:116912. doi: 10.1016/j.taap.2024.116912. Online ahead of print.ABSTRACTAnthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline ant...
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Mikito Hirakata Emi Tomikawa Chizuka Sakai Masashi Uchida Tsubasa Okano Reiko Shimozono Masakatsu Kawai Shoichi Itaba Lisa Munakata Ryo Suzuki Keiyu Oshida Source Type: research

L-Methionine accentuates anti-tumor action of Gefitinib in Gefitinib-resistant lung adenocarcinoma: Role of EGFR/ERK/AKT signaling and histone H3K36me2 alteration
In this study, we investigated the potential of L-Methionine in enhancing the cytotoxicity of Gefitinib and preventing resistance development. In vitro experiment employing the H1975 cell line demonstrated a notable enhancement in cytotoxic efficacy when L-Methionine (10 mM) was combined with Gefitinib, as indicated by a substantial reduction in IC50 values (155.854 ± 1.87 μM vs 45.83 ± 4.83 μM). Complementary in vivo investigations in a lung cancer model corroborated these findings. Co-administration of L-Methionine (100 mg/kg and 400 mg/kg) with Gefitinib (15 mg/kg) for 21 days exhibited marked improvements in therap...
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Swagata Pal Shaheen Wasil Kabeer Kulbhushan Tikoo Source Type: research

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study
CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.PMID:38521370 | DOI:10.1016/j.taap.2024.116909 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Juanjuan Zou Shengnan Qi Xiaojing Sun Yijing Zhang Yan Wang Yanzhong Li Ze-Hua Zhao Dapeng Lei Source Type: research

Cardioprotective potential of compound 3K, a selective PKM2 inhibitor in isoproterenol-induced acute myocardial infarction: A mechanistic study
This study demonstrates the cardioprotective potential of compound 3K in MI, and its mechanisms of cardioprotective action.PMID:38521371 | DOI:10.1016/j.taap.2024.116905 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Mohd Rihan Shyam Sunder Sharma Source Type: research

Ursolic acid alleviates meiotic abnormalities induced by 3-nitropropionic acid in mouse oocytes
Toxicol Appl Pharmacol. 2024 Mar 21:116910. doi: 10.1016/j.taap.2024.116910. Online ahead of print.ABSTRACT3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro ma...
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Tiancang Han Zhaoyang Sun Hongbo Zhang Yuhan Zhao Anhui Jiao Qingshan Gao Source Type: research

TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome
Toxicol Appl Pharmacol. 2024 Mar 21:116912. doi: 10.1016/j.taap.2024.116912. Online ahead of print.ABSTRACTAnthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline ant...
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Mikito Hirakata Emi Tomikawa Chizuka Sakai Masashi Uchida Tsubasa Okano Reiko Shimozono Masakatsu Kawai Shoichi Itaba Lisa Munakata Ryo Suzuki Keiyu Oshida Source Type: research

Ursolic acid alleviates meiotic abnormalities induced by 3-nitropropionic acid in mouse oocytes
Toxicol Appl Pharmacol. 2024 Mar 21:116910. doi: 10.1016/j.taap.2024.116910. Online ahead of print.ABSTRACT3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro ma...
Source: Toxicology and Applied Pharmacology - March 23, 2024 Category: Toxicology Authors: Tiancang Han Zhaoyang Sun Hongbo Zhang Yuhan Zhao Anhui Jiao Qingshan Gao Source Type: research