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Specialty: Toxicology

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Total 137 results found since Jan 2013.

Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture.
Abstract Romosozumab (EVENITYâ„¢ [romosozumab-aqqg in the US]) is a humanized monoclonal antibody that inhibits sclerostin and has been approved in several countries for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Sclerostin is expressed in bone and aortic vascular smooth muscle (AVSM). Its function in AVSM is unclear but it has been proposed to inhibit vascular calcification, atheroprogression, and inflammation. An increased incidence of positively adjudicated serious cardiovascular adverse events driven by an increase in myocardial infarction and stroke was observed in romosoz...
Source: Regulatory Toxicology and Pharmacology : RTP - June 22, 2020 Category: Toxicology Authors: Turk JR, Deaton AM, Yin J, Stolina M, Felx M, Boyd G, Bienvenu JG, Varela A, Guillot M, Holdsworth G, Wolfreys A, Dwyer D, Kumar SV, de Koning EM, Qu Y, Engwall M, Locher K, Ward LD, Glaus C, He YD, Boyce RW Tags: Regul Toxicol 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

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

Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy.
This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms. PMID: 32841740 [PubMed - as supplied by publisher]
Source: Toxicology Letters - August 21, 2020 Category: Toxicology Authors: Sousa LF, Bernardoni JL, Zdenek CN, Dobson J, Coimbra F, Gillett A, Lopes-Ferreira M, Moura-da-Silva AM, Fry BG Tags: Toxicol Lett 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

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

Taxon-selective venom variation in adult and neonate Daboia russelii (Russell's Viper), and antivenom efficacy
Toxicon. 2021 Nov 6:S0041-0101(21)00305-6. doi: 10.1016/j.toxicon.2021.11.004. Online ahead of print.ABSTRACTMajor variations in venom composition can occur between juvenile and adult venomous snakes. However, due to logistical constraints, antivenoms are produced using adult venoms in immunising mixtures, possibly resulting in limited neutralisation of juvenile snake venoms. Daboia russelii is one of the leading causes of snakebite death across South Asia. Its venom is potently procoagulant, causing stroke in prey animals but causing in humans consumptive coagulopathy-a net anticoagulant state-and sometimes death resultin...
Source: Toxicon - November 9, 2021 Category: Toxicology Authors: Christina N Zdenek Abhinandan Chowdhury Grace Y H Haw Aude Violette Rudy Fourmy Thomas Christ Freek J Vonk Bryan G Fry Source Type: research

Cerebral venous sinus thrombosis following Russell's viper (Daboia russelii) envenomation: A case report and review of the literature
We report a previously healthy middle-aged Indian female who developed cerebral venous sinus thrombosis preceded by features of disseminated bleeding diathesis following Russell's viper bite. The cerebral venous sinus thrombosis was diagnosed by magnetic resonance imaging. The patient responded well to treatment with antivenom and subcutaneous enoxaparin and had no demonstrable neurological deficits at three months of follow-up.PMID:36041514 | DOI:10.1016/j.toxicon.2022.08.014
Source: Toxicon - August 30, 2022 Category: Toxicology Authors: Ritwik Ghosh Mois és León-Ruiz Dipayan Roy Dinobandhu Naga Sona Singh Sardar Juli án Benito-León Source Type: research

Bisphenols induce cardiotoxicity in zebrafish embryos: Role of the thyroid hormone receptor pathway
In this study, we demonstrated that bisphenol A, S, and F (BPA, BPS, BPF) at environmental concentrations induced cardiotoxicity in zebrafish embryos. BPA decreased heart rate at 96 hpf (hours post fertilization) and increased the distance between the sinus venosus (SV) and bulbus arteriosus (BA), in zebrafish. BPF promoted heart pumping and stroke volume, shortened the SV-BAdistance, and increased body weight. Furthermore, we found that BPA increased the expression of the dio3b, thrβ, and myh7 genes but decreased the transcription of dio2. In contrast, BPF downregulated the expression of myh7 but upregulated that of thrÎ...
Source: Aquatic Toxicology - November 24, 2022 Category: Toxicology Authors: Jing-Yu Qin Wenyi Jia Shaoguo Ru Jiu-Qiang Xiong Jun Wang Weiwei Wang Liping Hao Xiaona Zhang Source Type: research

Understanding the molecular mechanisms of statin pleiotropic effects
Arch Toxicol. 2023 Apr 21. doi: 10.1007/s00204-023-03492-6. Online ahead of print.ABSTRACTStatins represent the cornerstone of pharmacotherapy for the prevention of atherosclerotic cardiovascular disease. These medications not only reduce low-density lipoprotein cholesterol (LDL-C) via inhibition of 3-hydroxy-3-methylglutarate attached to CoA reductase, the key rate-limiting step in the cholesterol biosynthetic pathway, but also upregulate expression of the low-density lipoprotein receptor, improving serum clearance. Given LDL-C is a causal risk factor for the development of atherosclerosis, these complementary mechanisms ...
Source: Archives of Toxicology - April 21, 2023 Category: Toxicology Authors: Charles A German James K Liao Source Type: research