The nitrite anion: the key intermediate in alkyl nitrates degradative mechanism.

Alkyl nitrates, _in vivo_, are metabolized to yield nitric oxide, and thiol groups are considered necessary cofactors. This statement is based on studies that underline how these species potentiate hemodynamic responsiveness to nitrates in patients with ischemic heart disease. However, the role of thiols might be mediated by the formation of corresponding S-nitrosothiols, and a redox process is responsible for the nitrates' degradation: an enzyme, probably the cytochrome P450, is involved _in vivo_. Here, we report evidence that, in vitro, no reaction between thiols and alkyl nitrates takes place, but that stronger reducing agents, such as iron (II) derivatives, are necessary: alkoxy radicals and the nitrite anion are the reaction intermediates. The latter, in slightly acidic conditions, for instance mimicking ischemic conditions, is shown to nitrosilate thiols to the corresponding S-nitrosothiols: the real NO suppliers. Therefore, the direct release of NO from nitrates is excluded. Finally, the in vivo role of thiols on depletion and tolerance is also accounted for

Hydrogen sulfide: a neurotransmitter or just a cofactor of the nitrite in the NO production?

Abstract. The hydrogen sulfide has been recently claimed to have an important role in the cardiovascular system, as well in the central nervous system, but its action seems directly connected to the presence of NO/NO-derivatives. We want to report here chemical evidences that suggest for the H 2 S a role as a cofactor, able to induce NO release from NO-donors, more than a direct neurotransmitter. In the last decade great attention has been devoted to the role of the hydrogen sulfide (H 2 S), in vivo , as a possible neurotransmitter, 1,2 and how it affects cardiovascular functions. 3,4 In the light of these stated roles, nowadays, particular attention is devoted to the possible synergy between H 2 S and NO; for example, the positive role of H 2 S in comparison to NO-releasers, i.e., increase of the NO production, 5 or the action of NO in inducing an increase of the amount of enzymes responsible of H 2 S production. Thus, in several physiological processes the direct interaction between

Nitric Oxide: Probably the in Vivo Mediator of the Bisulfite's Effects

The use of bisulfite in food and beverage preservation, as well as in commercial goods and phar- maceuticals as antimicrobial agents is well known, but not very much is reported on its action in vivo. It has been stressed that its action is connected to the presence of NO, and the only reported/ hypothesized evidence concerns the possible interaction with GSNO (S-nitrosoglutathione), an NO releaser. In this light, we investigated the interaction between GSNO and the bisulfite in an aqueous medium at pH = 6.4; actually, a positive effect of the sulfite was evidenced. i.e., the S-ni- trosoglutathione becomes a more efficient NO-releaser. But, the nitrite is the real pool of NO in vi- vo, therefore we investigate its interaction with the bisulfite in an aqueous acidic solution at pH = 6.4; this time, a definitely efficient and abundant NO release, 3.61 times higher compared to the GSNO, has been evidenced. Therefore, these results allow hypothesizing a fundamental role of NO in the bisulfite's action in vivo, or most probably the bisulfite acts simply as cofactor of NO-re- leasers

Simulation of capillary infiltration into packing structures by the Lattice-Boltzmann method for the optimization of ceramic materials

In this work we want to simulate with the Lattice-Boltzmann method in 2D the capillary infiltration into porous structures obtained from the packing of particles. The experimental problem motivating our work is the densification of carbon preforms by reactive melt infiltration. The aim is to determine optimization principles for the manufacturing of high-performance ceramics. Simulations are performed for packings with varying structural properties. Our analysis suggests that the observed slow infiltrations can be ascribed to interface dynamics. Pinning represents the primary factor retarding fluid penetration. The mechanism responsible for this phenomenon is analyzed in detail. When surface growth is allowed, it is found that the phenomenon of pinning becomes stronger. Systems trying to reproduce typical experimental conditions are also investigated. It turns out that the standard for accurate simulations is challenging. The primary obstacle to overcome for enhanced accuracy seems to be the over-occurrence of pinning

Nitric Oxide: The Key Molecule for Polyphenols Antimicrobial Action

The role of hydroxycinnamic acids as antioxidants, in vivo, has been widely discussed, but, recently, a great debate has focused on their antimicrobial ac- tion. In general, for the hydroxycinnamic acids’ action, the presence of NO, which is known to be an antimicrobial agent, seems compulsory; its produc- tion goes through the intermediacy of the nitrosonium ion, and a very low pH, for instance, as in the stomach, is requested. However, the action of the hydroxycinnamic acids seems to take place even in different biological com- partments, i.e., characterized by different pHs and conditions, and then, for NO production, an alternative mechanism could be involved. In this light, evidence for the NO formation, via an E.T. mechanism, even in mildly acidic conditions (pH = 6.4), was obtained by reacting an aqueous buffer solution of acidic nitrite (HNO2) with the hydroxycinnamic acids ferulic, caffeic, p-coumaric and sinapic. Experiments conducted by EPR spectroscopy, let to detect the NO formation, and the efficiency of the process depending on the available amount of free polyphenol, and the intrinsic nature of the hydroxycinnamic acids. Thus, the production of NO through a non-enzymatic mechanism, in light acidic conditions, would account for the antimicrobial action of hydroxycinnamic acids, even in unconventional biological compartments, and for NO as the key-molecule

Plasma Treated Water Solutions in Cancer Treatments: The Contrasting Role of RNS

Abstract: Plasma Treated Water Solutions (PTWS) recently emerged as a novel tool for the generation of Reactive Oxygen and Nitrogen Species (ROS and RNS) in liquids. The presence of ROS with a strong oxidative power, like hydrogen peroxide (H2O2), has been proposed as the main effector for the cancer‐killing properties of PTWS. A protective role has been postulated for RNS, with nitric oxide (NO) being involved in the activation of antioxidant responses and cell survival. However, recent evidences proved that NO‐derivatives in proper mixtures with ROS in PTWS could enhance rather than reduce the selectivity of PTWS‐induced cancer cell death through the inhibition of specific antioxidant cancer defenses. In this paper we discuss the formation of RNS in different liquids with a Dielectric Barrier Discharge (DBD), to show that NO is absent in PTWS of complex composition like plasma treated (PT)‐cell culture media used for in vitro experiments, as well as its supposed protective role. Nitrite anions (NO2‐) instead, present in our PTWS, were found to improve the selective death of Saos2 cancer cells compared to EA.hy926 cells by decreasing the cytotoxic threshold of H2O2 to non‐toxic values for the endothelial cell line