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Use of 2,2'-azobis(2-amidinopropane) dihydrochloride as a reagent tool for evaluation of oxidative stability of drugs.

PURPOSE: To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2'-Azobis(-amidinopropane) dihydrochloride (AAPH). METHODS: AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solution model, the drugs and AAPH were dissolved in a mixture of acetonitrile and aqueous buffer and incubated at elevated temperatures to evaluate oxidative degradation. The effects of pH and drug-AAPH ratio on the kinetics of the reaction were evaluated for compound A. Commonly used antioxidants were also evaluated by addition to solutions of drug and AAPH. In the solid-state model, blends of drug with microcrystalline cellulose were treated with AAPH and placed at elevated temperature and humidity to evaluate solid state oxidation. RESULTS: Use of AAPH resulted in selective oxidation of the model drugs by a free radical initiated process. The scope of the technique was further investigated in detail using compound A. The rate of oxidation of compound A varied directly with the concentration of AAPH. The pseudo first-order rate constants for the oxidative degradation were calculated from the kinetic data. The antioxidants were rank-ordered based on their quenching activity on the rates of AAPH initiated oxidation for compound A. The concept was extended to oxidation in solid state. CONCLUSIONS: The proposed AAPH model is useful in assessing oxidative stability of drug candidates in development.

Amidines↗

[Oxidative stability of the lipids in whitefish].

The manometric technique was employed to study the initiated oxidation of 7 samples of whitefish lipids of varying sites, to measure the kinetic parameters depending on the fatty acid composition and concentration of tocopherol. Changes in oxidative stability of lipids of varying localization was shown, a higher stability of muscle tissue lipids was noted as compared with brain and depot lipids. The possibility of testing oxidative stability of lipids according to the kinetic parameters is discussed.

Animals↗

Hydrogenation and interesterification effects on the oxidative stability and melting point of soybean oil.

Soybean oil with an iodine value of 136 was hydrogenated to have iodine values of 126 and 117. The soybean oils with iodine values of 136, 126, and 117 were randomly interesterified using sodium methoxide. The oxidative stabilities of the hydrogenated and/or interesterified soybean oils were evaluated by measuring the headspace oxygen content by gas chromatography, and the induction time was measured using Rancimat. The melting points of the oils were evaluated by differential scanning calorimetry. Duncan's multiple range test of the headspace oxygen and induction time showed that hydrogenation increased the headspace oxygen content and induction time at alpha = 0.05. Interesterification decreased the headspace oxygen and the induction time for the soybean oils with iodine values of 136, 126, and 117 at alpha = 0.05. Hydrogenation increased the melting points as the iodine value decreased from 136 and 126 to 117 at alpha = 0.05. The random interesterification increased the melting points of soybean oils with iodine values of 136, 126, and 117 at alpha = 0.05. The combined effects of hydrogenation and interesterification increased the oxidative stability of soybean oil at alpha = 0.05 and the melting point at alpha = 0.01. The optimum combination of hydrogenation and random interesterification can improve the oxidative stability and increase the melting point to expand the application of soybean oil in foods.

Calorimetry, Differential Scanning↗

Oxidative stability of algal oils as affected by their minor components.

Algal oils, namely, arachidonic acid single-cell oil (ARASCO), docosahexaenoic acid single-cell oil (DHASCO), and a single-cell oil rich in both docosahexaenoic acid and docosapentaenoic acid (OMEGA-GOLD oil), were evaluated for their oxidative stability, as such and after stripping of their minor components, in the dark at 60 degrees C and under fluorescent light at 27 degrees C. Several analytical methods were used to assess the oxidative stability of these oils. Oil extracts were also investigated for their scavenging of 1,1-diphenyl-2-picrylhydrazyl radical by a spectrophotometric method and by measuring their total phenolic contents. The results indicated that minor oil constituents play a major role in their oxidative stability in the dark as well as under fluorescent light. The stability of the oils was dictated by their fatty acid composition, total tocopherols, and the type of pigment present. DHASCO contained a significant level of natural radical scavengers and phenolic compounds that contributed to its higher stability compared to the ARASCO and OMEGA-GOLD oils. Thus, the importance of minor components in the stability of the oils examined was demonstrated.

Arachidonic Acid↗

Effect of vitamin A on the oxidative stability of broiler meat during storage: lack of interactions with vitamin E.

1. An experiment was carried out with male broiler chicks to evaluate the combined effect of two concentrations of vitamin A (1.032 and 10.32 mg retinyl acetate/kg diet) and two concentrations of vitamin E (0 and 150 mg alpha-tocopheryl acetate/kg diet) on the oxidative stability of the drumstick meat of broiler chickens. The experimental diets were fed from 1 to 42 d of age. The oxidative stability, evaluated by thiobarbituric acid reactive substances (TBARS) values, was determined after 125 d of storage at -18 degrees C. 2. TBARS values were very low and not significantly affected by dietary vitamins A and E or their combinations. However, the TBARS values in the meat of birds fed on the vitamin E-free diets, but not on the vitamin E-supplemented diets, were markedly increased after using an accelerated test of oxidation of the meat lipids by incubation. This resulted in a significant (P<0.001) difference from vitamin E supplementation. Vitamin A, alone or in combination with vitamin E, did not affect TBARS values found after incubation. 3. It is concluded that vitamin A at the concentrations used had no effect on the oxidative stability of the meat, in contrast to the protective effect of vitamin E, and that there is no interaction between the effect of these two vitamins on meat stability.

Animal Feed↗

Influence of high-oryzanol rice bran oil on the oxidative stability of whole milk powder.

The effect of high oryzanol rice bran oil (RBO) on the oxidative stability of low-heat and high-heat whole milk powder (WMP) was investigated. Milk (3.6% fat) was fortified with RBO at 0.1 and 0.2% (wt/wt) and was concentrated and dried. Control WMP was made without RBO addition. Thiobarbituric acid reactive substances (TBARS) were used to monitor oxidation during storage at 45 degrees C for 40 d. The oxidation of low-heat WMP was significantly reduced by addition of 0.1% RBO, but there was no significant effect on the oxidation of high-heat WMP. An increase of RBO to 0.2% did not significantly improve the oxidative stability when compared with 0.1% RBO. The TBARS in RBO-fortified, low-heat WMP increased with storage time up to 30 d but decreased with further storage to 40 d. The TBARS in all high-heat WMP and low-heat control WMP increased up to 20 d storage and then decreased with further storage. The most likely reason for this increase was due to the reaction of TBARS with milk proteins. Addition of RBO reduced the L (lightness) value and increased the b (yellowness) value but had no effect on the a (redness) value. When compared with the control milk powder, consumers could not detect any effect on the flavor of the reconstituted 0.1% RBO WMP but could detect a flavor difference in the 0.2% RBO WMP.

Animals↗

Macrocyclic aromatic ether-imide-sulfones: versatile supramolecular receptors with extreme thermochemical and oxidative stability.

Macrocyclic receptors having extreme thermo-oxidative stability, and which bind a wide range of electron-donor substrates via pi-stacking donor-acceptor interactions, are accessible by cycloimidization of an amine-functionalized aryl ether-sulfone with pyromellitic dianhydride or 1,4,5,8-naphthalenetetracarboxylic dianhydride. The potential of these receptors in supramolecular chemistry is illustrated, for example, by the spontaneous self-assembly and crystallization of a five-component [3]pseudorotaxane from a solution of its constituents.

Journal Article↗

Antioxidant evaluation and oxidative stability of structured lipids from extravirgin olive oil and conjugated linoleic acid.

Structured lipid (SL) was synthesized from extravirgin olive oil (EVOO) and conjugated linoleic acid (CLA) via a lipase-catalyzed reaction. CLA provides a variety of health benefits, but it is not consumed in free fatty acid form. The synthesized SL olive oil contained 42.5 mol % CLA isomers, and the major isomers were cis-9,trans-11-CLA (16.9 mol %) and trans-10,cis-12-CLA (24.2 mol %). The antioxidant activity determined by the radical scavenging capacity with the 2,2-diphenyl-1-picrylhydrazyl radical was lower in SL olive oil than in EVOO. The oxidative stability was also lower in SL olive oil since it had a higher peroxide value, rho-anisidine value, and 2-thiobarbituric acid reactive substances values during 20 days of storage at 60 degrees C. This observation could be due to the reduction in the natural phenolic compounds (97%) and tocopherols (56%), and the incorporated CLA with two conjugated double bonds in the SL olive oil. The oxidative stability of SL olive oil was increased by added rosemary extracts at concentrations of 100, 200, and 300 ppm. The present study suggests that the SL olive oil may be a suitable way to incorporate or deliver CLA into human diets. However, the addition of a proper antioxidant would be required for improving its oxidative stability.

Antioxidants↗

Oxidative stability of low density lipoproteins and vitamin E levels increase in maternal blood during normal pregnancy.

In 24 healthy pregnant women, parameters related to the oxidative stability of low density lipoproteins (LDL) were determined at three times during pregnancy and shortly after delivery. The fatty acid composition of plasma phospholipids (PL) and the plasma concentrations of vitamin E, vitamin A, and beta-carotene were assessed in the same samples. Total triglyceride (TG), total cholesterol, LDL-cholesterol, and high density lipoprotein (HDL)-cholesterol concentrations were also determined. The length of the lag phase of isolated LDL challenged with Cu2+ ions significantly increased with the progression of pregnancy. The oxidation rate and the amount of conjugated dienes formed increased and reached a maximum at 29-37 wk of pregnancy. Total TG, cholesterol, and LDL-cholesterol reached a maximum in the third trimester of pregnancy. beta-Carotene remained stable, vitamin A decreased, and vitamin E significantly increased throughout pregnancy. Vitamin E plasma concentration correlated positively with the length of the lag phase. The increased levels of vitamin E could contribute to the higher resistance of LDL toward oxidation with progressing gestation, measured by the prolonged lag phase. Furthermore, vitamin E plasma levels correlated positively with TG concentration but not with LDL-cholesterol. The level of polyunsaturated fatty acids in PL decreased with the progression of pregnancy. No correlation was found between the fatty acid composition of plasma PL, nor with the cholesterol concentration, and the parameters studied related to the oxidative stability of LDL. The major finding of this study is the increased oxidative resistance of LDL with progressing gestation.

Adult↗

Impact of whey protein emulsifiers on the oxidative stability of salmon oil-in-water emulsions.

To obtain a better understanding of how the interfacial region of emulsion droplets influences lipid oxidation, the oxidative stability of salmon oil-in-water emulsions stabilized by whey protein isolate (WPI), sweet whey (SW), beta-lactoglobulin (beta-Lg), or alpha-lactalbumin (alpha-La) was evaluated. Studies on the influence of pH on lipid oxidation in WPI-stabilized emulsions showed that formation of lipid hydroperoxides and headspace propanal was much lower at pH values below the protein's isoelectric point (pI), at which the emulsion droplets were positively charged, compared to that at pH values above the pI, at which the emulsion droplets were negatively charged. This effect was likely due to the ability of positively charged emulsion droplets to repel cationic iron. In a comparison of lipid oxidation rates of WPI-, SW-, beta-Lg-, and alpha-La-stabilized emulsions at pH 3, the oxidative stability was in the order of beta-Lg > or = SW > alpha-La > or = WPI. The result indicated that it was possible to engineer emulsions with greater oxidative stability by using proteins as emulsifier, thereby reducing or eliminating the need for exogenous food antioxidants.

Drug Stability↗

Effects of silage species and supplemental vitamin E on the oxidative stability of milk.

Two experiments were conducted to study the effects of feeding legume silages and providing supplemental vitamin E in concentrates on the oxidative stability of milk. In experiment 1, six multiparous Holstein-Friesian cows were offered 1 of 6 silage treatments in a cyclical changeover-design experiment, with four 4-wk periods. The silages were grass, red clover, white clover, alfalfa, grass and red clover mixture (50:50 on a DM basis), and grass and white clover mixture (50:50 on a DM basis). In experiment 2, 8 cows were used in a changeover-design experiment with three 4-wk periods. The 4 treatments were a factorial combination of forages (grass silage or red clover silage) and supplemental vitamin E in the form of all-rac-alpha-tocopheryl acetate (29 or 290 IU/kg of DM in the concentrate). All forages were offered ad libitum and a flat rate of concentrates (8 kg/d) was fed in both experiments. Red clover silage led to significantly higher forage intakes, milk yields, and milk protein percentage in experiment 2, which was in agreement with results from experiment 1. There was no effect of vitamin E on feed intake, milk production, or milk fat and protein percentage. Red clover silage also led to significant changes in milk fatty acid profiles, particularly increased levels of polyunsaturated fatty acids. Milk samples were stored at 4 degrees C and 20 degrees C and analyzed for alpha-tocopherol and thiobarbituric acid reactive substances at intervals to determine oxidative stability. Diets based on red clover and alfalfa silages were associated with more rapid loss of alpha-tocopherol and increased production of thiobarbituric acid reactive substances during the storage of milk in comparison with diets based on grass silage. The increased oxidative deterioration of milk produced from cows fed red clover silage was avoided by vitamin E supplementation.

Animal Feed↗

Increasing the oxidative stability of liquid and dried tuna oil-in-water emulsions with electrostatic layer-by-layer deposition technology.

Omega-3 Fatty acids have numerous health benefits, but their addition to foods is limited by oxidative rancidity. Engineering the interfacial membrane of oil-in-water emulsion droplets to produce a cationic and/or thick interface is an effective method to control lipid oxidation. Cationic and thick emulsion droplet interfacial membranes can be produced by an electrostatic layer-by-layer deposition technique resulting in droplets that are coated by multiple layers of emulsifiers. Tuna oil-in-water emulsion droplets coated by lecithin and chitosan produce cationic emulsion droplets that are more oxidatively stable than emulsions coated by lecithin alone. Ethylenediaminetetraacetic acid (EDTA) was able to increase the oxidative stability of emulsions stabilized with lecithin and chitosan more effectively than mixed tocopherols. The combination of EDTA and mixed tocopherols was not more effective than EDTA alone suggesting that control of prooxidant metals was the most important antioxidant technology. The production of emulsion droplets coated with lecithin and chitosan could be an excellent technology for stabilization of oxidatively unstable lipids for use in a variety of food products.

Animals↗

Microencapsulation and oxidative stability of spray-dried fish oil emulsions.

Emulsions of menhaden oil and sodium caseinate (NaCas) incorporating carbohydrates of varying dextrose equivalence (DE) were spray-dried to yield encapsulated fish oil powders. The effects of carbohydrate DE (5.5-38), core/wall ratio and NaCas/carbohydrate ratio on microencapsulation efficiency (ME) and oxidative stability of spray-dried emulsions were examined. The effect of alpha-tocopherol or Trolox C addition on the oxidative stability of herring oil emulsions and powders was also determined. ME of fish oil powders was greater than 90% in most cases. Peroxide value (PV) of menhaden oil powders decreased on increasing the DE of carbohydrates. PV of menhaden oil powders increased as core/wall ratio increased from 0.33-1.0. NaCas/DE 28 ratio did not affect PV values of powders. The addition of alpha-tocopherol or Trolox C decreased PV throughout the storage period; this effect was most pronounced for alpha-tocopherol added to the oil at a concentration of 100 ppm. Addition of alpha-tocopherol delays the onset of oxidation in stored fish oil powders.

Antioxidants↗

Effect of high levels of dietary iron, iron injection, and dietary vitamin E on the oxidative stability of turkey meat during storage.

A study was carried out to evaluate the combined effect of excess Fe, supplied either in the diets (Experiments 1, 2, and 3) or by injection (Experiment 4), and various levels of dietary vitamin E on the oxidative stability of the thigh muscle of turkeys stored at -18 C for various periods. Iron was added to a commercial diet that already contained 20 mg/kg supplemental Fe, at concentrations of 0, 100, 250, and 500 mg/kg as ferrous sulfate or injected as Fe-dextran to the left drumstick muscle (total amount of 1.2 g per turkey). Vitamin E was added to the experimental diets not already supplemented with this vitamin, at levels of 0, 28, and 150 mg/kg. Thiobarbituric acid reactive substances (TBARS) values of the meat gradually increased as its storage duration increased from about 15 to 120 d. Increasing dietary Fe supplementation from 0 to 500 mg/kg tended to decrease TBARS values in one experiment only; otherwise, this variable was not affected by dietary Fe level. Injection of Fe significantly (P < 0.05) increased TBARS values, only in meat from the injected side. The TBARS values of the meat up to about 30 d of storage were significantly lower due to the supplementation of the diet with vitamin E at a level of 28 mg/kg in one out of three experiments and at a level of 150 mg/kg in two out of two experiments. The protective effect of the higher level of vitamin E remained evident after about 108 d of storage. No interaction was observed between Fe and vitamin E treatments in their effect on TBARS values. Blood hemoglobin concentrations were significantly increased by the supplementation of the diet with the high levels of Fe, in one experiment only. This variable was consistently and significantly increased from about 10 to 23 wk of age. The results show that high levels of dietary Fe do not adversely affect the oxidative stability of thigh meat of turkey; however, stability might be reduced by injected Fe. Dietary vitamin E, at a level of 150 mg/kg, consistently increased this stability.

Aging↗

Antioxidant activity of gamma-oryzanol: mechanism of action and its effect on oxidative stability of pharmaceutical oils.

Gamma-oryzanol, a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities; in particular, it has antioxidant properties and is often used in cosmetic formulations as a sunscreen. The first objective of the present investigation was to elucidate the molecular mechanism(s) of the antioxidant activity of gamma-oryzanol by utilising different in vitro model systems, such as scavenging of stable DPPH radical, OH and O2- radicals scavenging, and azocompound AMVN-initiated lipid peroxidation. The effect of gamma-oryzanol on the oxidative stability of vegetable oils of pharmaceutical and cosmetic interest was then evaluated in a oxidation accelerate test and compared with the effect of the well-known antioxidants BHA and BHT. Our results demonstrate that gamma-oryzanol is an organic radical scavenger able to prevent AMVN-triggered lipoperoxidation. Moreover, when added to oils at concentrations ranging between 2.5 and 10 mmol/kg, gamma-oryzanol shows a dose-dependent increase of the induction times; in particular, it improved the oxidative stability of oils very prone to lipoperoxidation because of their high content of polyunsaturated fatty acids. On the ground of our results, we can conclude that gamma-oryzanol may have a potential application for the stabilization of lipidic raw materials.

Antioxidants↗

Effect of dietary fish oil substitution with linseed oil on the performance, tissue fatty acid profile, metabolism, and oxidative stability of Atlantic salmon.

The objective of this experiment was to test the effect of total or partial substitution of dietary fish oil (FO) by linseed oil (LO) in Atlantic salmon feeding on performance, liver and muscle fatty acid composition, selected lipogenic and lipolytic enzyme activities, and flesh oxidative stability. For 12 wk, fish (220 +/- 12 g of initial BW) were fed five experimental diets in which the FO was serially replaced by 25, 50, 75, and 100% LO. Total FO replacement by LO did not (P = 0.20) affect fish final weight, biometric indices, or i.m. fat contents. Liver and muscle neutral lipid (NL) composition responded to dietary treatments in different ways. Whereas the sum of n-3 PUFA in muscle followed a linear and quadratic pattern with increasing levels of LO, a linear (P = 0.005) effect was observed in the liver NL fraction. Total n-3 and n-6 PUFA contents in the polar lipid fraction (PL) were unaffected (P = 0.356) by dietary input of LO in muscle. Activity of liver glucose-6-P-dehydrogenase (G6PD) was greater with increasing levels of LO (P = 0.004). A time effect (P < 0.001) was observed in the concentration of lipid peroxidation products, expressed as thiobarbituric acid reactive substances, in fish flesh stored under refrigeration for 9 d; however, the progressive inclusion of LO in the feed did not affect (P = 0.125) flesh oxidation stability. In summary, LO can totally replace FO in Atlantic salmon feed without affecting growth performance and muscle susceptibility to lipid oxidation. Fatty acid metabolism in the liver was affected by LO, promoting G6PD activity and eicosatetraenoic acid accumulation; however, a 100% LO replacement decreased (P < 0.001) concentrations of eicosapentaenoic and docosahexaenoic acids in salmon muscle.

Animal Feed↗

Improvement of oxidative stability of conjugated linoleic acid (CLA) by microencapsulation in cyclodextrins.

Oxidative stability of conjugated linoleic acid (CLA) encapsulated in alpha-, beta-, and gamma-cyclodextrins (designated CLA/CDs microencapsules) was studied by measuring the headspace-oxygen depletion in airtight serum bottles and by measuring the peroxide values (POV). The rate of oxygen depletion was reduced from 41.0 (control) to 21.5, 2.1, 1.2, and 1.1 micromol/L.h(-)(1) by CLA/alpha-CD microencapsules at 1:1, 1:2, 1:4, and 1:6 mole ratios, respectively, indicating that CLA oxidation was completely protected by a 1:4 mole ratio of CLA/alpha-CD. Such a protective effect by CLA/beta-CD or CLA/gamma-CD microencapsules was achieved at a 1:6 mole ratio, but the effect by CLA/beta-CD was slightly greater than that by CLA/gamma-CD. The protective effect of alpha-, beta-, and gamma-CDs for CLA oxidation was confirmed by their POV-reducing abilities in CLA/CDs. These results suggest that alpha-CD was the most effective for the protection of CLA oxidation by microencapsulation, followed by beta-CD and gamma-CD.

Cyclodextrins↗

Enhanced oxidative stability of a hydrophilic arginine-conjugated linoleic acid complex.

The application of conjugated linoleic acid (CLA) as a functional food ingredient has been limited due to its high cost of purification and insolubility in water. Recently, we reported a method to produce high-purity CLA using two-step urea-inclusion crystallization and a hydrophilic arginine-CLA (Arg-CLA) complex. The present study compared the oxidative stability and antioxidant activity of CLA and Arg-CLA. Hydroperoxide production from CLA increased about 12-fold at 10 hr after heat treatment at 100(R)C, whereas Arg-CLA did not exhibit significant hydroperoxide production. Furthermore, the Arg-CLA complex showed synergistic antioxidant activity in a 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical scavenging assay. Arg-CLA at 20 mM scavenged 89% of ABTS radicals in 3 h, whereas CLA alone quenched only 48% under the same conditions. Our results indicate that a hydrophilic Arg-CLA exhibits enhanced oxidative stability and antioxidant activity, which could expand the scope of CLA application in various food industries.

Antioxidants↗