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The mitigation of nitrosamine formation in drug products has been studied and approaches such as using formulations with pH modifiers and antioxidants have been shown to decrease the formation of nitrosamines. However, more studies are needed to explore the effectivness of mitigation strategies with different drug models and formulations. The primary objective of this work was to assess the role of different antioxidants and pH modifiers in tablet formulations to mitigate the formation of NDMA, prepared in-house, using metformin hydrochloride as a model drug. A study design for manufacturing metformin hydrochloride formulations was created to evaluate potential mitigation stratigies. The formulations were prepared by wet granulation that included a sodium nitrite spike and various antioxidants such as ascorbic acid, caffeic acid and ferulic acid at various concentrations that may inhibit nitrosamine formation. The study design also included pH modifiers such as hydrochloric acid and sodium carbonate. The metformin hydrochloride formulations were placed under stability conditions that included humidity, temperature and time over a six month period. NDMA inhibition was found to be most effective in formulations with basic pH, followed by the addition of tested antioxidants with 0.1% concentrations in the formulations. All tested antioxidants showed complete mitigation in formulations with 0.5% and 1% concentrations. In summary, basic pH and the inclusion of antioxidants exhibited the potential to mitigate the formation of NDMA in metformin hydrochloride tablets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

This study aimed to evaluate a pomegranate peel extract (PPE), selected for its level of phytochemical compounds and antioxidant activities, as a nitrite substitute in dry sausages, as well as its effect on lipid and protein oxidative changes and instrumental colour during the drying period (28 days). Of the extraction solvents screened, water: acetone 3:7 (v/v) was the most effective extraction solvent, yielding extracts with the highest content of phenolic compounds, flavonoids and condensed tannins and antioxidant activities (ABTS, DPPH and FRAP). Four batches of dry sausages were produced with different incoming amounts of sodium nitrite (NaNO 2 ) and PPE: 1) 150 ppm NaNO 2 ; 2) 0 ppm NaNO 2 ; 3) 0 ppm NaNO 2  + 1% PPE (v/w) and 4) 0 ppm NaNO 2  + 2% PPE (v/w). Nitrite removal increased lipid oxidation in uncured dry sausages, while nitrite and PPE caused lower TBA-RS values in cured and PPE treated sausages. During drying, both nitrite and PPE addition significantly decreased carbonyl and thiol contents compared to the uncured dry sausages. A dose-response was found for PPE, with lower carbonyl and thiol concentrations, the higher the level of PPE added. PPE significantly modified instrumental colour coordinates L*a*b* producing significant total colour changes compared to cured dry sausages., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ramon Cava Lopez reports financial support and administrative support were provided by FEDER and JUNTA DE EXTREMADURA., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ferrous oxyhemoglobin (HbO 2 ) in red blood cells (RBCs) invariably and slowly autoxidizes to form ferric methemoglobin (metHb). However, the level of metHb is always maintained below 0.5% by intracellular metHb reduction of enzymatic systems with coenzymes, such as reduced nicotinamide adenine dinucleotide (NADH), and by superoxide dismutase (SOD) and catalase (CAT), which eliminate reactive oxygen species. Unquestionably, NADH cannot reduce metHb without the corresponding enzymatic system. Our study, however, demonstrated that a high concentration of NADH (100-fold of normal level, equimolar to HbO 2 ) retarded autoxidation of HbO 2 in a highly purified Hb solution with no enzymatic system. Furthermore, an inhibitory effect of NADH on metHb formation was observed with additions of oxidants such as H 2 O 2 , NO, and NaNO 2 . Our mechanism assessment elucidated extremely high pseudo-CAT and pseudo-SOD activities of NADH with coexistence of HbO 2 , and reactivity of NADH with NO. We prepared a model of RBCs (Hb-vesicles, Hb-V) encapsulating purified HbO 2 solution and NADH, but no enzymatic system within liposome. We confirmed the inhibitory effect of NADH on both autoxidation and oxidant-induced metHb formation. In addition, an intravenous administration of these Hb-Vs to rats caused significant retardation of metHb formation by approximately 50% compared to the case without NADH coencapsulation. Based on these results, we elucidated a new role of NADH, that is, antioxidative effect via interaction with Hb, in addition to its classical role as a coenzyme.

Peroxynitrite and heme peroxidases (or heme)-H 2 O 2 -NaNO 2 system are the two common ways to cause protein tyrosine nitration in vitro, but the effects of antioxidants on reducing these two pathways-induced protein nitration and oxidation are controversial. Both nitrating systems can dose-dependently induce triosephosphate isomerase (TIM) nitration, however, heme-H 2 O 2 -NaNO 2 was less destructive to protein secondary structures and led to more nitrated tyrosine residue than 3-morpholinosydnonimine hydrochloride (SIN-1, a peroxynitrite donor). Both of desferrioxamine and catechin could inhibit TIM nitration induced by heme-H 2 O 2 -NaNO 2 and SIN-1 and protein oxidation induced by SIN-1, but promoted heme-H 2 O 2 -NaNO 2 -induced protein oxidation. Moreover, the antagonism of natural phenolic compounds on SIN-1-induced tyrosine nitration was consistent with their radical scavenging ability, but no similar consensus was found in heme-H 2 O 2 -NaNO 2 -induced nitration. Our results indicated that peroxynitrite and heme-H 2 O 2 -NaNO 2 -induced protein nitration was different, and the later one could be a better model for anti-nitration compounds screening., (© 2017 Wiley Periodicals, Inc.)

The effect of sodium ascorbate (SA; 500, 750, 1000 mg/kg) and sodium nitrite (SN; 40, 80, 120 mg/kg) doses on the shelf-life stability of liver pâtés was investigated in a full factorial design. Clear dose-dependent responses of the added SN or SA were found for the concentrations of nitrite, ascorbic acid and dehydroascorbic acid in the raw batters and in the cooked pâtés before and after 48 h of chilled display. Decreasing the SN dose to 80 mg/kg had no negative impact on the colour stability (a* value) and lipid oxidation (TBARS), and no additional antioxidant effect of SA was noticed. Lowering SN to 40 mg/kg resulted in proper colour formation, but the colour stability was inferior and lipid oxidation increased. Yet, increasing the amount of SA, at this low SN dose, resulted in lower TBARS values. Decreasing the SN dose to 80 or 40 mg/kg had no distinct effect on protein oxidation, which was however only measured by carbonyl content., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Lycopene is a lipophilic antioxidant that is largely transported in human blood by Low Density Lipoproteins (LDL). One of the early events in the aetiology of atherosclerosis is thought to be the oxidation of LDL. Myeloperoxidase an enzyme secreted by neutrophils and macrophages is thought to oxidise human LDL particles. In this study, isolated human LDL was challenged with myeloperoxidase or copper, and the LDL was screened for lipoperoxidation and oxidation of apolipoprotein B100, depletion of lycopene and oxidation of cholesterol. Myeloperoxidase induced oxidation of LDL through direct interaction with apolipoprotein B100. No lipoperoxidation was observed following myeloperoxidase treatment; however, 7-ketocholesterol was detected indicating the products of myeloperoxidase interact with the surface of the LDL particles. Lycopene does react with the products of myeloperoxidase in solvent, but played no role in protecting against enzyme derived oxidation of human LDL.

Coffee is one of the most widely consumed beverages worldwide. Evidence of the health benefits and the important contribution of coffee brew to the intake of anti-oxidants in the diet has increased coffee consumption. Chlorogenic acid (ChA) and caffeic acid (CaA) are the major phenolic compounds in coffee. However, phenolic compounds, which are generally effective anti-oxidants, can become pro-oxidants in the presence of Cu(2+) to induce DNA damage under certain conditions. On the other hand, sodium nitrite (NaNO(2)) is widely used as a food additive to preserve and tinge color on cured meat and fish. It is possible that phenolic compounds react with NaNO(2) under acidic conditions, such as gastric juice. In this study, we identified compounds produced by the reaction between ChA or CaA in coffee and NaNO(2) in artificial gastric juice. The identified phenolic compounds and nitrated phenolic compounds were assessed for their anti-oxidant, pro-oxidant, and nitration activities by performing an in vitro assay. The nitrated phenolic compounds seemed to show increased anti-oxidant activity and decreased pro-oxidant activity. However, one nitrated CaA compound that has a furoxan ring showed the ability to release NO(2)(-) in the neutral condition., (Copyright © 2011 Elsevier Inc. All rights reserved.)