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Neuroprotective effects of Lasmiditan and Sumatriptan in an experimental model of post-stroke seizure in mice: Higher effects with concurrent opioid receptors or K < sub > ATP < /sub > channels inhibitors
CONCLUSION: Lasmiditan and sumatriptan significantly increased post-stroke seizure thresholds in mice by suppressing inflammatory cytokines and neuronal apoptosis. Lasmiditan and sumatriptan seem to exert higher effects on seizure threshold with concurrent administration of the opioid receptors or KATP channels modulators.PMID:36155770 | DOI:10.1016/j.taap.2022.116254
Source: Toxicology and Applied Pharmacology - September 26, 2022 Category: Toxicology Authors: Maryam Shayan Faezeh Eslami Arash Amanlou Shahabaddin Solaimanian Nastaran Rahimi Amir Rashidian Shahram Ejtemaei-Mehr Mehdi Ghasemi Ahmad-Reza Dehpour Source Type: research

Identification of novel and potential PPAR γ stimulators as repurposed drugs for MCAO associated brain degeneration
Toxicol Appl Pharmacol. 2022 May 9:116055. doi: 10.1016/j.taap.2022.116055. Online ahead of print.ABSTRACTPeroxisome proliferator-activated receptor-gamma (PPARγ) has been shown to have therapeutic promise in the treatment of ischemic stroke and is supported by several studies. To identify possible PPARγ activators, the current study used an in silico technique in conjunction with molecular simulations and in vivo validation. FDA-approved drugs were evaluated using molecular docking to determine their affinity for PPARγ. The findings of molecular simulations support the repurposing of rabeprazole and ethambutol for the ...
Source: Toxicology and Applied Pharmacology - May 13, 2022 Category: Toxicology Authors: Halima Usman Zhen Tan Mehreen Gul Sajid Rashid Tahir Ali Fawad Ali Shah Shupeng Li Jing Bo Li Source Type: research

Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies
In this study, we used human induced pluripotent stem cell (hiPSC)-derived embryoid bodies (EB) as an in vitro model to investigate the embryotoxic effects of a carefully selected set of pharmacological compounds. Morphology, viability, and differentiation potential were investigated after exposing EBs to folic acid, all-trans-retinoic acid, dexamethasone, and valproic acid for 15 days. The results showed that the compounds differentially repressed cell growth, compromised morphology, and triggered apoptosis in the EBs. Further, transcriptomics was employed to compare subtle temporal changes between treated and untreated c...
Source: Toxicology and Applied Pharmacology - November 7, 2021 Category: Toxicology Authors: Vijay Bhaskar Reddy Konala Swapna Nandakumar Harshini Surendran Savita Datar Ramesh Bhonde Rajarshi Pal Source Type: research

U0126 pretreatment inhibits cisplatin-induced apoptosis and autophagy in HEI-OC1 cells and cochlear hair cells.
Abstract Deafness is the most common sensory disorder in the world. Ototoxic drugs are common inducing factors of sensorineural hearing loss, and cochlear hair cell (HC) damage is the main concern of the present studies. Cisplatin is a widely used, highly effective antitumor drug, but some patients have experienced irreversible hearing loss as a result of its application. This hearing loss is closely related to HC apoptosis and autophagy. U0126 is a specific inhibitor of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signaling pathway and has neuroprotective effects. For example, the neuroprot...
Source: Toxicology and Applied Pharmacology - February 9, 2021 Category: Toxicology Authors: Wang D, Shi S, Ren T, Zhang Y, Guo P, Wang J, Wang W Tags: Toxicol Appl Pharmacol Source Type: research

Cardiopulmonary function and dysregulated cardiopulmonary reflexes following acute oleoresin capsicum exposure in rats.
Abstract Cardiopulmonary functions such as respiratory depression, severe irritation, inflamed respiratory tract, hyperventilation and, tachycardia are the most affected ones when it comes to the riot control agent oleoresin capsicum (OC) exposure. However, no studies have been done to elucidate the mechanism underlying deterioration of the combined cardiopulmonary functions. Parameters such as acute respiratory, cardiac, parameters and ultrasonography (USG) measurements were investigated in an in vivo setup using Wistar rats at 1 h and 24 h post inhalation exposure to 2%, 6% and 10% OC, whereas, cell migratio...
Source: Toxicology and Applied Pharmacology - August 13, 2020 Category: Toxicology Authors: Patowary P, Pathak MP, Kishor S, Roy PK, Das S, Chattopadhyay P, Zaman K Tags: Toxicol Appl Pharmacol Source Type: research

Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1.
This study shows that CR inhalation exposure induces real-time and persistent vascular changes that promote hypotension-a known risk factor for stroke. Because of continued widespread exposures of humans to combustion-derived CR (environmental and tobacco products), CR may be an important cardiovascular disease risk factor. PMID: 32634517 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - July 3, 2020 Category: Toxicology Authors: Lynch J, Jin L, Richardson A, Jagatheesan G, Lorkiewicz P, Xie Z, Theis WS, Shirk G, Malovichko M, Bhatnagar A, Srivastava S, Conklin DJ Tags: Toxicol Appl Pharmacol Source Type: research

Melatonin's efficacy in stroke patients; a matter of dose? A systematic review.
Abstract There is a lack of effective therapies for stroke patients; its treatment is even more difficult considering the unexpected onset of the disease. In the last decade, melatonin has emerged as a promising neuroprotective agent which is able to cross the blood-brain-barrier (BBB) and with a low toxicity profile. The aim of this systematic review was to summarize and critically review clinical and pre-clinical evidence related to melatonin's effectiveness as a stroke treatment. Together with a comparative dose extrapolation with those used in the selected randomized controlled trials (RCTs), and based on thes...
Source: Toxicology and Applied Pharmacology - February 25, 2020 Category: Toxicology Authors: Ramos E, Farré-Alins V, Egea J, López-Muñoz F, Reiter RJ, Romero A Tags: Toxicol Appl Pharmacol Source Type: research

Realgar and cinnabar are essential components contributing to neuroprotection of Angong Niuhuang Wan with no hepatorenal toxicity in transient ischemic brain injury.
In this study, we compared the neuropharmacological effects of AGNHW and modified AGNHW in an experimental ischemic stroke rat model. Male SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Although oral administration of AGNHW for 7 days in the rats increased arsenic level in the blood and liver tissue, there were no significant changes in the arsenic level in kidney, mercury level in the blood, liver and kidney as well as hepatic and renal functions in MCAO rats. AGNHW revealed neuroprotective properties by reducing infarction volume, preserving blood-brain barrier in...
Source: Toxicology and Applied Pharmacology - June 13, 2019 Category: Toxicology Authors: Tsoi B, Wang S, Gao C, Luo Y, Li W, Yang D, Yang D, Shen J Tags: Toxicol Appl Pharmacol Source Type: research

The interaction of zinc and the blood-brain barrier under physiological and ischemic conditions.
Abstract Zinc is the second most abundant metal in human and serves as an essential trace element in the body. During the past decades, zinc has been found to play important roles in central nervous system, such as the development of neurons and synaptic activities. An imbalance of zinc is associated with brain diseases. The blood-brain barrier (BBB) maintains the homeostasis of the microenvironment, regulating the balance of zinc in the brain. A compromised BBB is the main cause of severe complications in cerebral ischemic patients, such as hemorrhage transformation, inflammation and edema. Recent studies reporte...
Source: Toxicology and Applied Pharmacology - December 27, 2018 Category: Toxicology Authors: Qi Z, Liu KJ Tags: Toxicol Appl Pharmacol Source Type: research

Sodium tanshinone IIA sulfonate promotes endothelial integrity via regulating VE-cadherin dynamics and RhoA/ROCK-mediated cellular contractility and prevents atorvastatin-induced intracerebral hemorrhage in zebrafish.
Abstract Impaired vascular integrity leads to serious cerebral vascular diseases such as intracerebral hemorrhage (ICH). In addition, high-dose statin therapy is suggested to cause increased ICH risk due to unclear effects of general inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) on the vascular system. Here we evaluated the protective effects of sodium tanshinone IIA sulfonate (STS), which has high efficacy and safety in clinical studies of ischemic stroke, by using atorvastatin (Ator) induced ICH zebrafish embryos and human umbilical vein endothelial cells (HUVECs). By using double transgenic Tg(...
Source: Toxicology and Applied Pharmacology - May 3, 2018 Category: Toxicology Authors: Zhou ZY, Huang B, Li S, Huang XH, Tang JY, Kwan YW, Hoi PM, Lee SM Tags: Toxicol Appl Pharmacol Source Type: research

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