Myeloperoxidase: a potential therapeutic target for coronary artery disease
EXPERT OPINION ON THERAPEUTIC TARGETS
Authors: Chaikijurajai, Thanat; Tang, W. H. Wilson
Abstract
Introduction: Coronary artery disease (CAD) poses significant morbidity and mortality globally. Despite significant advances in treatment interventions, residual cardiovascular risks remain unchecked. Recent clinical trials have shed light on the potential therapeutic benefits of targeting anti-inflammatory pathways. Myeloperoxidase (MPO) plays an important role in atherosclerotic plaque formation and destabilization of the fibrous cap; both increase the risk of atherosclerotic cardiovascular disease and especially CAD. Areas covered: This article examines the role of MPO in the pathogenesis of atherosclerotic CAD and the mechanistic data from several key therapeutic drug targets. There have been numerous interesting studies on prototype compounds that directly or indirectly attenuate the enzymatic activities of MPO, and subsequently exhibit atheroprotective effects; these include aminobenzoic acid hydrazide, ferulic acid derivative (INV-315), thiouracil derivatives (PF-1355 and PF-06282999), 2-thioxanthines derivative (AZM198), triazolopyrimidines, acetaminophen, N-acetyl lysyltyrosylcysteine (KYC), flavonoids, and alternative substrates such as thiocyanate and nitroxide radical. Expert opinion: Future investigations must determine if the cardiovascular benefits of direct systemic inhibition of MPO outweigh the risk of immune dysfunction, which may be less likely to arise with alternative substrates or MPO inhibitors that selectively attenuate atherogenic effects of MPO.
Assesment of hematotoxic, oxidative and genotoxic damage potentials of fipronil in rainbow trout Oncorhynchus mykiss, Walbaum
TOXICOLOGY MECHANISMS AND METHODS
Authors: Ucar, Arzu; Parlak, Veysel; Cilingir Yeltekin, Asli; Ozgeris, Fatma Betul; Caglar, Ozge; Turkez, Hasan; Alak, Gonca; Atamanalp, Muhammed
Abstract
In this study, changes in the blood tissue of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) caused by Fipronil (FP) insecticide were investigated using different biomarkers (Hematology parameters, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA), paraoxonase (PON), arylesterase (ARE), myeleperoxidase (MPO), micronucleus (MN), 8-hydroxy-2-deoxyguanosine (8-OHdG)) level and caspase-3 activity. Statistically significant alterations in hematology parameters occurred with FP effect. In blood tissue, dose-dependent inhibition was determined in SOD-CAT-GPX-PON and ARE enzyme activities, but MDA and MPO were induced statistically significant. The results of MN assay were compared with the control group and it was obtained that genotoxicity of different dose groups was similar. The level of 8-OHdG and the activity and caspase-3 examined in blood tissue was increased depending on the dose. It was determined with different biomarkers that this insecticide caused physiological stress changes in the tissues examined.