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Source: Toxicology and Applied Pharmacology

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Total 118 results found since Jan 2013.

Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF- κB signal pathway.
Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF-κB signal pathway. Toxicol Appl Pharmacol. 2018 May 27;: Authors: Ma B, Zhu J, Zhao A, Zhang J, Wang Y, Zhang H, Zhang L, Zhang Q Abstract Osteosarcoma (OS) is the most frequent and high mortality primary bone tumor in the adolescent. And it is well-known for poor prognosis due to high incidence of metastasis. Raddeanin A (RA), an active component of Anemone raddeana Regel, showed potential anti-cancer activities. However, the anti-tumor effect and molecular mechanism(s) of RA o...
Source: Toxicology and Applied Pharmacology - May 27, 2018 Category: Toxicology Authors: Ma B, Zhu J, Zhao A, Zhang J, Wang Y, Zhang H, Zhang L, Zhang Q Tags: Toxicol Appl Pharmacol Source Type: research

cAMP/PKA/EGR1 signaling mediates the molecular mechanism of ethanol-induced inhibition of placental 11 β-HSD2 expression.
This study aimed to investigate the molecular mechanism of the prenatal ethanol exposure (PEE)-induced inhibition of placental 11β-HSD2 expression. Pregnant Wistar rats were intragastrically administered ethanol (4 g/kg d) from gestational days 9 to 20. The levels of maternal and fetal serum corticosterone and placental 11β-HSD2-related gene expression were analyzed. Furthermore, we investigated the mechanism of reduced placental 11β-HSD2 expression induced by ethanol treatment (15-60 mM) in HTR-8/SVneo cells. In vivo, PEE decreased fetal body weights and increased maternal and fetal serum corticosterone and early...
Source: Toxicology and Applied Pharmacology - May 23, 2018 Category: Toxicology Authors: Yu L, Zhou J, Zhang G, Huang W, Pei L, Lv F, Zhang Y, Zhang W, Wang H Tags: Toxicol Appl Pharmacol Source Type: research

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces hepatic steatosis and endoplasmic reticulum stress by inducing nuclear factor erythroid-derived 2-related factor 2 nuclear translocation.
Abstract Activation of endoplasmic reticulum (ER) stress is involved in the development of nonalcoholic fatty liver disease. Glucagon-like peptide-1 (GLP-1) has been reported to reduce hepatic steatosis, but the underlying mechanism has not been fully elucidated. Here, we investigated whether exendin-4 (EX-4), a GLP-1 receptor analogue, improves hepatic steatosis through ER stress reduction. Furthermore, we explored which ER stress pathway is involved in this process, with a focus on the protein kinase RNA-like ER kinase (PERK)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway. EX-4 treatment redu...
Source: Toxicology and Applied Pharmacology - September 22, 2018 Category: Toxicology Authors: Yoo J, Cho IJ, Jeong IK, Ahn KJ, Chung HY, Hwang YC Tags: Toxicol Appl Pharmacol Source Type: research

Role of Mcl-1 in regulation of cell death in human induced pluripotent stem cell-derived cardiomyocytes in vitro.
Abstract Targeting the anti-apoptotic protein Mcl-1 holds a promise to improve therapy of multiple types of Mcl-1 dependent cancers but raises concerns of on-target cardiotoxicity due to the presence and reported role of Mcl-1 in heart. Herein, we investigated the importance of Mcl-1 in the survival and contractile function of human pluripotent stem cell-derived cardiomyocytes in culture. Effective knockdown of Mcl-1 with siRNAs reproducibly resulted in early (measured at Day 3) marginal alterations in caspase 3/7 activity, LDH leakage, ATP content and cellular impedance. After 14 days of Mcl-1 knockdown, loss o...
Source: Toxicology and Applied Pharmacology - September 27, 2018 Category: Toxicology Authors: Guo L, Eldridge S, Furniss M, Mussio J, Davis M Tags: Toxicol Appl Pharmacol Source Type: research

Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting the TXNIP-NLRP3 inflammasome.
Abstract Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We...
Source: Toxicology and Applied Pharmacology - October 4, 2018 Category: Toxicology Authors: Liang H, Gao J, Zhang C, Li C, Wang Q, Fan J, Wu Z, Wang Q Tags: Toxicol Appl Pharmacol Source Type: research

Induction of endoplasmic reticulum stress might be responsible for defective autophagy in cadmium-induced prostate carcinogenesis.
Abstract Earlier, we reported that chronic cadmium (Cd)-exposure to prostate epithelial (RWPE-1) cells causes defective autophagy, which leads to the transformation of a malignant phenotype in both in vitro and in vivo models. However, the upstream events responsible for defective autophagy are yet to be delineated. The present study suggests that chronic Cd exposure induces endoplasmic reticulum (ER) stress that triggers the phosphorylation of stress transducers [protein kinase R-like ER Kinase- (PERK), eukaryotic translation initiation factor 2-alpha- (eIF2-α) and Activating Transcription Factor 4 -(ATF-4)], re...
Source: Toxicology and Applied Pharmacology - April 15, 2019 Category: Toxicology Authors: Kolluru V, Tyagi A, Chandrasekaran B, Ankem M, Damodaran C Tags: Toxicol Appl Pharmacol Source Type: research

Contact allergen (PPD and DNCB)-induced keratinocyte sensitization is partly mediated through a low molecular weight hyaluronan (LMWHA)/TLR4/NF- κB signaling axis.
In conclusion, keratinocyte contact allergen-dependent sensitization is partly mediated through a LMWHA/TLR4/ NF-κB signaling axis. PMID: 31226360 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - June 17, 2019 Category: Toxicology Authors: Kavasi RM, Berdiaki A, Spyridaki I, Papoutsidakis A, Corsini E, Tsatsakis A, Tzanakakis G, Dragana N Tags: Toxicol Appl Pharmacol Source Type: research

Icariin protects rotenone-induced neurotoxicity through induction of SIRT3.
This study aimed to determine whether ICA exerts neuroprotective effects on rotenone (ROT)-induced neurotoxicity through activation of SIRT3. Rats treated with ROT exhibited a marked loss of dopamine (DA) neurons and a decline in motor function, along with a decrease in protein expressions of SIRT3 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the substantia nigra (SN). Administration of ICA significantly alleviated the loss of DA neurons, improved behavioral function, and concomitantly enhanced SIRT3 and PGC-1α expressions. The neuroprotective effect of ICA on ROT-induced cytotoxic...
Source: Toxicology and Applied Pharmacology - June 24, 2019 Category: Toxicology Authors: Zeng R, Wang X, Zhou Q, Fu X, Wu Q, Lu Y, Shi J, Klaunig JE, Zhou S Tags: Toxicol Appl Pharmacol Source Type: research

ROS -mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro.
Abstract Juglone (JG) exhibits a broad-spectrum of cytotoxicity against some cancer cells. However, its molecular mechanisms have not been investigated well. Here, the present results showed that JG significantly inhibited tumor growth in vivo. CCK-8 assays, flow cytometric analysis, western blotting and immunohistochemistry revealed that JG effectively inhibited cell proliferation and induced apoptosis through extrinsic pathways. We also observed that JG treatment induced autophagy flux via activiting the AMPK-mTOR signaling pathway. In addition, we found that JG enhanced p53 activation by increasing down-regulat...
Source: Toxicology and Applied Pharmacology - July 4, 2019 Category: Toxicology Authors: Wang P, Zhang SD, Jiao J, Wang W, Yu L, Zhao XL, Wang LT, Meng D, Fu YJ Tags: Toxicol Appl Pharmacol Source Type: research

H1R mediates local anesthetic-induced vascular permeability in angioedema.
This study supported a key role of H1R in LA-induced angioedema, and suggested that in the design of LA structure, the ring formation of the N-methyl scaffold on the side chain can properly avoid the angioedema. PMID: 32061592 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - February 11, 2020 Category: Toxicology Authors: Cao J, Zhang Y, Che D, Liu R, Yang L, Zhang T, He L Tags: Toxicol Appl Pharmacol Source Type: research

Group II muscarinic acetylcholine receptors attenuate hepatic injury via Nrf2/ARE pathway.
Abstract Parasympathetic nervous system dysfunction is common in patients with liver disease. We have previously shown that muscarinic acetylcholine receptors (mAchRs) play an important role in the regulation of hepatic fibrosis and that the receptor agonists and antagonists affect hepatocyte proliferation. However, little is known about the impact of the different mAchR subtypes and associated signaling pathways on liver injury. Here, we treated the human liver cell line HL7702 with 10 mmol/L carbon tetrachloride (CCL4) to induce hepatocyte damage. We found that CCL4 treatment increased the protein levels of gr...
Source: Toxicology and Applied Pharmacology - March 27, 2020 Category: Toxicology Authors: Luo L, Zhang G, Mao L, Wang P, Xi C, Shi G, Leavenworth JW Tags: Toxicol Appl Pharmacol Source Type: research

Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer.
Abstract Cancer mortality is mainly caused by metastasis, which requires dynamic remodeling of cytoskeletal components such as microtubules. Targeting microtubules presents a promising antimetastatic strategy that could prevent cancer spreading and recurrence. It is known that arsenic trioxide (ATO) is able to inhibit the migration and invasion of solid malignant tumors, but its exact molecular mechanism remains unclear. Here, we report a novel molecular target and antimetastatic mechanism of ATO in head and neck squamous cell carcinoma (HNSCC). We found that cytoplasmic linker protein 170 (CLIP170) was overexpres...
Source: Toxicology and Applied Pharmacology - July 23, 2020 Category: Toxicology Authors: Gao L, Xue B, Xiang B, Liu KJ Tags: Toxicol Appl Pharmacol Source Type: research

Hesperetin protects against palmitate-induced cellular toxicity via induction of GRP78 in hepatocytes.
In conclusion, hesperetin protected against palmitate-induced hepatic cell death via activation of the sXBP1/GRP78 signaling pathway, thus inhibiting palmitate-induced ER stress. Moreover, high concentrations of hesperetin induce ER stress and subsequently cause cell death in hepatocytes. PMID: 32763355 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - August 4, 2020 Category: Toxicology Authors: Geng Y, Wu Z, Buist-Homan M, Blokzijl H, Moshage H Tags: Toxicol Appl Pharmacol Source Type: research

Oxymatrine ameliorates Imiquimod-induced psoriasis pruritus and inflammation through inhibiting heat shock protein 90 and heat shock protein 60 expression in keratinocytes.
Abstract In this work, we aimed to investigate whether oxymatrine exerts its anti-pruritic and anti-inflammatory efficacy in the imiquimod-induced psoriasis mice and the related mechanism. We established the psoriasis model by applying the imiquimod ointment topically and oxymatrine was injected intraperitoneally as the treatment. The behavior and skin morphology results indicated that oxymatrine inhibits imiquimod-induced pruritus alleviating keratinization of skin and inflammatory infiltration. Moreover, we examined the expression of various indicators and found heat shock protein (HSP) 90 and 60 upregulated in ...
Source: Toxicology and Applied Pharmacology - August 20, 2020 Category: Toxicology Authors: Xiang X, Tu C, Li Q, Wang W, Huang X, Zhao Z, Xiong H, Mei Z Tags: Toxicol Appl Pharmacol Source Type: research

Soybean lectin induces autophagy through P2RX7 dependent activation of NF- κB-ROS pathway to kill intracellular mycobacteria.
Conclusion Taken together, these results conclude that SBL induced autophagy exerts an anti-mycobacterial effect in P2RX7-NF-κB dependent manner through the generation of ROS. General significance This study has provided a novel anti-mycobacterial role of SBL, which may play an important role in devising new therapeutic interventions. PMID: 33301752 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - December 7, 2020 Category: Toxicology Authors: Mishra A, Behura A, Kumar A, Ghosh A, Naik L, Mawatwal S, Mohanty SS, Mishra A, Saha S, Bhutia SK, Singh R, Dhiman R Tags: Toxicol Appl Pharmacol Source Type: research