Search results for "Peroxynitrous acid"
showing 10 items of 23 documents
New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid agains…
2015
Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ…
Formation of 2-nitrophenol from salicylaldehyde as a suitable test for low peroxynitrite fluxes
2016
There has been some dispute regarding reaction products formed at physiological peroxynitrite fluxes in the nanomolar range with phenolic molecules, when used to predict the behavior of protein-bound aromatic amino acids like tyrosine. Previous data showed that at nanomolar fluxes of peroxynitrite, nitration of these phenolic compounds was outcompeted by dimerization (e.g. biphenols or dityrosine). Using 3-morpholino sydnonimine (Sin-1), we created low fluxes of peroxynitrite in our reaction set-up to demonstrate that salicylaldehyde displays unique features in the detection of physiological fluxes of peroxynitrite, yielding detectable nitration but only minor dimerization products. By mean…
Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol–induced neuronal nitric oxide synthase uncoupling in met…
2020
Abstract 2-methoxyestradiol (2-ME) is a physiological anticancer compound, metabolite of 17β-estradiol. Previously, our group evidenced that from mechanistic point of view one of anticancer mechanisms of action of 2-ME is specific induction and nuclear hijacking of neuronal nitric oxide synthase (nNOS), resulting in local generation of nitro-oxidative stress and finally, cancer cell death. The current study aims to establish the substantial mechanism of generation of reactive nitrogen species by 2-ME. We further achieved to identify the specific reactive nitrogen species involved in DNA-damaging mechanism of 2-ME. The study was performed using metastatic osteosarcoma 143B cells. We detected…
Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets
2008
Aggregation of activated platelets is considerably mediated by the autocrine action of thromboxane A2 (TxA2) which is formed in a prostaglandin endoperoxide H2 synthase-1 (PGHS-1 or COX-1)-dependent manner. The activity of PGHS-1 can be stimulated by peroxides, an effect termed "peroxide tone", that renders PGHS-1 the key regulatory enzyme in the formation of TxA2. Activated platelets release nitric oxide (*NO) and superoxide (O*2) but their interactions with the prostanoid pathway have been controversially discussed in platelet physiology and pathophysiology. The current study demonstrates that endogenously formed peroxynitrite at nanomolar concentrations, originating from the interaction …
Drugs modulating the biological effects of peroxynitrite and related nitrogen species.
2007
The term “reactive nitrogen species” includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape. The array of affected chemical and pathological processes is extremely broad. One of the most conspicuous mechanisms observed thus far has been the scavenging of the peroxynitrite anion by molecules endowed with antioxidant activity. T…
Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.
2007
Background— We have recently demonstrated that activity of red blood cell glutathione peroxidase-1 is inversely associated with the risk of cardiovascular events in patients with coronary artery disease. The present study analyzed the effect of glutathione peroxidase-1 deficiency on atherogenesis in the apolipoprotein E-deficient mouse. Methods and Results— Female apolipoprotein E-deficient mice with and without glutathione peroxidase-1 deficiency were placed on a Western-type diet for another 6, 12, or 24 weeks. After 24 weeks on Western-type diet, double-knockout mice (GPx-1 −/− ApoE −/− ) developed significantly more atherosclerosis than control apolipoprotein E-deficient mice. Moreover…
Isoprenylhydroquinone glucoside: a new non-antioxidant inhibitor of peroxynitrite-mediated tyrosine nitration
2004
Abstract Three hydroquinone glucosides and four caffeoylquinic esters were examined for their effect on tyrosine nitration, as well as on the oxidation of dihydrorhodamine (DHR) 123 and cytochrome c 2+ induced by peroxynitrite. All these phenolics, which had previously been characterized as the active principles of the plant Phagnalon rupestre , were fairly active in preventing the oxidation of DHR 123, though inefficient in the cytochrome c test. While their antioxidant potency is associated with the presence of a caffeoyl moiety, not so an obvious chemical character was correlated to a greater activity against nitration of tyrosine. Here, the highest potency corresponded to 2-isoprenylhyd…
Metal ions modify DNA-protecting and mutagen-scavenging capacities of the AV-153 1,4-dihydropyridine.
2019
Abstract 1,4-Dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. AV-153-Na, an antimutagenic and DNA-repair enhancing compound was shown to interact with DNA by intercalation. Here we studied DNA binding of several AV-153 salts to evaluate the impact of AV-153 modifications on its DNA binding capacity, the ability to scavenge the peroxynitrite, to protect HeLa and B-cells cells against DNA damage. Affinity of the AV-153 salts to DNA measured by a fluorescence assay was dependent on the metal ion forming a salt in position 4 of the 1,4-DHP, and it decreased as follows: Mg > Na > Ca > Li > Rb > K. AV-153-…
Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside.
2007
The nitration of tyrosine caused by peroxynitrite and other reactive nitrogen species is clearly detrimental for some physiological processes; however, its signalling role is still open to controversy. Among the natural phenolics known for their ability to oppose free tyrosine nitration, isoprenylhydroquinone glucoside is investigated due to its unusual structure, which contains a simple hydroxybenzene alkylated by a hemiterpenoid moiety. This hydroquinone was shown to be an effective inhibitor of peroxynitrite-induced protein tyrosine nitration in 3T3 fibroblasts. When tested on bovine seroalbumin nitration, however, the potency was reduced by half and the effect was almost abolished in th…
Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species.
2008
Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate. When studied on the intracellular protein tyrosine nitration induced by ONOO- in cultured murine fibroblasts as well a…