NADPH-dependent Lipid Peroxidation Research Articles

MODELING IN VITRO PATHWAYS OF ACTIVATION OF LIPID PEROXIDATION AND PROTEIN IN CHRONIC KIDNEY DISEASE

We studied the spontaneous and metal induced oxidation of lipids and proteins in in vitro modeling ways of lipid peroxidation and blood proteins in the formation of malondialdehyde (MDA) and protein carbonyl groups (PCG) in 86 patients with chronic pyelonephritis (cPN) and 64 patients chronic glomerulonephritis(cGN) without prejudice excretory function of the kidneys. Installed the increase in the blood of patients with cPN MDAs 2 times, MDAe--14%, PCG 1.5 times; and cGN--MDAs 2.3 times, MDAe--29%, PCG--2 times. Found increased MDA content and PCG in the blood of patients with cPN and more expressive when cGN. Stimulation of in vitro peroxidation processes contributed significantly increased of production of MDA comparedwith baseline. In the modeling in vitro ascorbate-dependent and NADPH-dependent lipid peroxidation ways and the increase in protein production of MDA and PCG in both groups of patients, especially in the NADPH-dependent way, which must be considered in the correction of oxidative processes and antioxidant therapy appointment.

Synthesis and Evaluation of Antioxidant Properties of Novel 2‐[2‐(4‐chlorophenyl) benzimidazole‐1‐yl]‐N‐(2‐arylmethylene amino) acetamides and 2‐[2‐(4‐chlorophenyl) benzimidazole‐1‐yl]‐N‐(4‐oxo‐2‐aryl‐thiazolidine‐3‐yl) acetamides‐I

Our approach was to synthesize and examine the antioxidant properties of some new 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(2-arylmethyleneamino) acetamide (1-18) and 2-[2-(4-chlorophenyl)benzimidazole-1-yl]-N-(4-oxo-2-aryl-thiazolidine-3-yl)acetamide (1t-18t) derivatives. Their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation levels (LP assay) and microsomal ethoxyresorufin O-deethylase activities (EROD assay) were determined. The free radical scavenging properties of the compounds were also examined in vitro determining the interaction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The compounds showed significant effects in the above tests.

Mechanism of paraquat-stimulated lipid peroxidation in mouse brain and pulmonary microsomes

Paraquat-stimulated NADPH-dependent lipid peroxidation in mouse brain and pulmonary microsomes was inhibited by superoxide dismutase and singlet oxygen quenchers, but not by catalase or hydroxyl radical scavengers. MnCl2, which might form a salt with unsaturated lipid, inhibited the lipid peroxidation in brain microsomes, but not that in pulmonary microsomes. These findings suggest that activated oxygen species, especially superoxide and singlet oxygen, may play a major role in the stimulation of microsomal lipid peroxidation by paraquat in both brain and lung, and that the nature of the lipids exposed to peroxidative attack may be different in microsomes of the two organs.

Antioxidant and Antifungal Properties of Benzimidazole Derivatives

Antioxidant and radical scavenging properties of a series of 2-[4-(substituted piperazin-/piperidin-1-ylcarbonyl)phenyl]-1H-benzimidazole derivatives were examined. Free radical scavenging properties of compounds 11-30 and 33 were evaluated for the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide anion radical. In addition the inhibitory effects on the NADPH-dependent lipid peroxidation levels were determined by measuring the formation of 2-thiobarbituric acid reactive substances (TBARS) using rat liver microsomes. Compound 33 which has a p-fluorobenzyl substitutent at position 1 exhibited the strongest inhibition (83%) of lipid peroxidation at a concentration of 10(-3) M, while the nonsubstituted analogue 13 caused 57% inhibition. This result is fairly consistent with the antimicrobial activity results against both Staphylococcus aureus and Candida albicans.

ChemInform Abstract: Synthesis and Antioxidant Properties of Some New Flavone Derivatives on Lipid Peroxidation in the Rat Liver.

A series of 2'-, 3'-, 4'- and 6-substituted flavone derivatives was synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. Retinoic acid, at 10(-4) M concentration, decreased the LP level by about 34%. A significant decrease in male liver microsomal LP level was noted for the compounds 3d, 1a, 3b and 4b at a concentration of 10(-4) M (100%, 95%, 75% and 62%, respectively).

Synthesis and evaluation of N-substituted indole-3-carboxamide derivatives as inhibitors of lipid peroxidation and superoxide anion formation

The in vitro antioxidant effects of novel N-substituted indole-3-carboxamides (I3CDs) 1-10 on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels and their free radicals scavenging properties were determined by the inhibition of superoxide anion formation (SOD). Among the synthesized compounds, 4, 5, 8 and 9 significantly inhibited SOD with an inhibition range at 84–100% at 10− 3 M concentration. The presence of halo substituents both ortho- and para- positions of these compounds resulted 100% inhibition of SOD. Comparison the activity results of halogenated and non-halogenated derivatives suggested that the halogenated compounds are more active than the non-halogenated compounds. On the other hand, the introduction of a para fluoro benzyl in the 1-position of indole (compounds 7, 8) has more impact on the SOD inhibition when the benzamide ring was mono halogenated. However, none of other compounds had a significant inhibitory effects on the level of lipid peroxidation.

Toxicological assessment of indium nitrate on aquatic organisms and investigation of the effects on the PLHC-1 fish cell line

Indium nitrate is mainly used as a semiconductor in batteries, for plating and other chemical and medical applications. There is a lack of available information about the adverse effects of indium compounds on aquatic organisms. Therefore, the toxic effects on systems from four trophic levels of the aquatic ecosystem were investigated. Firstly, the bacterium Vibrio fischeri, the alga Chlorella vulgaris and the cladoceran Daphnia magna were used in the toxicological evaluation of indium nitrate. The most sensitive model was V. fischeri, with a NOAEL of 0.02 and an EC(50) of 0.04 mM at 15 min. Although indium nitrate should be classified as harmful to aquatic organisms, it is not expected to represent acute risk to the aquatic biota. Secondly, PLHC-1 fish cell line was employed to investigate the effects and mechanisms of toxicity. Although protein content, neutral red uptake, methylthiazol metabolization, lysosomal function and acetylcholinesterase activity were reduced in cells, stimulations were observed for metallothionein levels and succinate dehydrogenase and glucose-6-phosphate dehydrogenase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. To clarify the main events in PLHC-1 cell death induced by indium nitrate, nine modulators were applied. They were related to oxidative stress (alpha-tocopherol succinate, mannitol and sodium benzoate), disruption of calcium homeostasis (BAPTA-AM and EGTA), thiol protection (1,4-dithiotreitol), iron chelation (deferoxiamine) or regulation of glutathione levels (2-oxothiazolidine-4-carboxylic acid and malic acid diethyl ester). The main morphological alterations were hydropic degeneration and loss of cells. At least, in partly, toxicity seems to be mediated by oxidative stress, and particularly by NADPH-dependent lipid peroxidation.

Synthesis, antifungal and antioxidant screening of some novel benzimidazole derivatives

Some novel benzimidazole derivatives were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) level, ethoxyresorufin O-deethylase (EROD) and antifungal activities were determined. A significant decrease in male rat liver microsomal LP level was noted by compounds 4c (52%), 4e (58%) and 4h (43%) at 10− 3 M concentration. Compounds 4c (100.0%), 4h (100.0%), 5c (98.0%) and 5h (100.0%) inhibited the microsomal ethoxyresorufin O-deethylase (EROD) enzyme activity better than that of the specific inhibitor caffeine (85%). Among these compounds, only compounds 4b and 4h exhibited moderate activity against C.albicans whereas the others had weak effects.

Hepatoprotective Efficacy of Pyrimidine Derivatives in Acute Dichloroethane Intoxication

The paper presents the results of a study of the antioxidative and hematoprotective properties of pyrimidine derivatives: 1,3,6-trimethyl-5-hydroxyuracil and 3,6-dimethyl-5-hydrpxyuracil versus the synthetic antioxidant tonarol, а-tocopherol acetate, and the antihypoxant ethomerzole. In model systems of varying complexity, the antiradical activity of pyrimidines and their effects on spontaneous, ascorbate- and NADPH-dependent lipid peroxidation processes, as well as their protective activity were studied in different types of hypoxia. The pyrimidine derivatives were found to have the high antioxidative activity comparable with that of ionol. 1,3,6-trimethyl-5-hydroxyuracil has antihypoxic activity. Dichloroethane induced acute toxic hepatitis whose major manifestations were cytolysis, cholestasis, lipid metabolic disturbances, and an activated lipid peroxidation response. 1,3,6-trimethyl-5-hydroxyuracil limits the cytotoxic and cholestatic activity of dichloroethane, stabilizes lipid metabolism and lipid peroxidation reactions, and increases life span and survival in rats.

A study on the antioxidant activities of some new benzazole derivatives

The in vitro antioxidant properties of some new benzazole derivatives (1-10) such as benzoxazoles, benzimidazoles, and benzothiazoles were determined by their effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) level, the scavenging of superoxide anion and the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 1, 2, 4 and 6, showed potent scavenging effect on superoxide radical at 10(-3) M. Compound 8, 5-nitro-2-(phenoxymethyl)benzimidazole, strongly inhibited lipid peroxidation at 10(-3) M concentration.

Scavenging of Reactive Oxygen Species by Eriobotrya japonica Seed Extract

We have clarified that Eriobotrya japonica seed extract has strong antioxidative activity, and is effective for the prevention and treatment of various diseases, such as hepatopathy and nephropathy. In this study, to investigate the influences of components of Eriobotrya japonica seed extract on its antioxidative activity, extracts were prepared using various solvents (n-hexane (Hex), ethyl acetate (EtOAc), n-butanol (n-BuOH), methanol (MeOH) and H2O) and the antioxidative activity of the solvent fractions and components was evaluated based on the scavenging of various radicals (DPPH and O2(-)) measured by the ESR method and the inhibition of Fe3+-ADP induced NADPH dependent lipid peroxidation in rat liver microsomes. The radical scavenging activities and inhibitory activities on lipid peroxidation differed among the solvent fractions and components. In the n-BuOH, MeOH and H2O fractions, radical scavenging activity and inhibitory activity on lipid peroxidation were high. In addition, these fractions contained abundant polyphenols, and the radical scavenging activity increased with the polyphenol content. In the low-polar Hex and EtOAc fractions, the radical scavenging activity was low, but the lipid peroxidation inhibition activity was high. These fractions contained beta-sitosterol, and the inhibitory activity on lipid peroxidation was high. Based on these findings, the antioxidative activity of Eriobotrya japonica seed extract may be derived from many components involved in a complex mechanism, resulting in high activity.

Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity

The six novel 4-methylcoumarins bearing different functionalities such as amino, hydroxy, N-acetyl, acetoxy and nitro have been synthesized and confirmed on the basis of their spectral data ( 1H-, 13C-NMR, UV, IR and EI mass). They were examined for the first time for their effect on NADPH dependent liver microsomal lipid peroxidation in vitro, and the results were compared with other model 4-methylcoumarin derivatives to establish the structure–activity relationship. Our studies demonstrated that amino group is an effective substitute for the hydroxyl group for antioxidant property and produced a dramatic inhibition of lipid peroxidation. Ortho dihydroxy and ortho hydroxy-amino coumarins were found to possess highest antioxidant and radical scavenging activities.

Syntheses of Novel Indole Lipoic Acid Derivatives and Their Antioxidant Effects on Lipid Peroxidation

The aim of the study was to examine antioxidant properties of conjugates based on indole and lipoic acid moieties. The design and syntheses of novel indole alpha-lipoic acid derivatives were performed. The antioxidant properties of target compounds were investigated using rat liver microsomal, NADPH-dependent lipid peroxidation inhibition. Some of the target compounds, especially those containing amide linker at position 5 of indole ring, proved to be highly effective in inhibiting lipid peroxidation as compared to alpha-lipoic acid.

Antioxidant Properties of Novel Benzimidazole Retinoids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Antioxidant properties of flavone-6(4')-carboxaldehyde oxime ether derivatives.

The in vitro antioxidant properties of some flavone-6(4)-carboxaldehyde oxime ether derivatives (Ia-f, IIa-f) were determined by their effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels by measuring the formation of 2-thiobarbituric acid reactive substances. The free radical scavenging properties of the compounds were also examined in vitro by determining their capacity to scavenge superoxide anions and interact with the stable free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The most active compounds, IIb (Flavone-4'-carboxaldehyde-O-ethyl oxime) and Id (Flavone-6-carboxaldehyde-O-[2-(1-pyrolidino) ethyl] oxime), caused 98 and 79% inhibition of superoxide anion production and DPPH stable free radical at 10(-3) M, respectively.

Synthesis and Antioxidant Properties of Novel Benzimidazole Derivatives

Some novel benzimidazole derivatives carrying thiosemicarbazide and triazole moieties at the N1 position were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels determined by measuring the formation of 2-thiobarbituric acid reactive substance. The free radical scavenging properties of the compounds were also examined in vitro by determining the capacity to scavenge superoxide anion formation and the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The compounds showed a significant effect in the above tests except to scavenge superoxide anion formation.

Antioxidant properties of novel benzimidazole retinoids.

Our approach was to examine the antioxidant activity of novel retinoid derivatives containing the benzimidazole moiety. Their in vitro effects on rat liver microasomal, NADPH-dependent lipid peroxidation levels and superoxide anion formation were determined. Lipid peroxidation in rat liver microsomes was reduced by some of the compounds in a dose-dependent manner.

Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver.

Some benzimidazole derivatives namely 1-[(substituted thiocarbamoylhydrazine carbonyl) methyl]-2-phenyl-1H-benzimidazoles (1a-13a), N-[(2-phenylbenzimidazol-1-yl methyl)-[1,3,4]-thiadiazole-2-yl]-substituted phenyl amines (1b-13b) and 5-(2-phenyl benzimidazol-1-yl-methyl)-4-substituted phenyl-4H-1,2,4-triazole-3-thiones (1c-13c) were synthesized, and their in vitro effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. The most active compound 10a caused an 84% inhibition of LP at 10(-3) M, which is better than that of butylated hydroxytoluene (BHT) (65%).

Evaluation of the antioxidant effects of some flavonylthiazolidinediones by determining their effects on lipid peroxidation, superoxide anion formation, and 2,2-diphenyl-1-picrylhydrazyl stable free radical.

The in vitro antioxidant effects of some flavonylthiazolidinediones (Ia-d, IIa-d) on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined by measuring the formation of 2-thiobarbituric acid reactive substance. The free radical-scavenging properties of the compounds were examined in vitro by determining the capacity to scavenge superoxide anion formation and of the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The compounds had no inhibitory effects on LP. However, they had variable inhibitory influence on superoxide anion production and DPPH radical in a concentration-dependent manner. The most active compound, 3-(2,5-dimethoxyphenacyl)-5-[2-phenyl-4H-4-oxo-1-benzopyran-6-yl)methylenyl]-thiazolidine-2,4-dione, Id showed 98% inhibition of superoxide anion production and 95% inhibition of DPPH stable free radical at 10(-3) M.

ANTIOXIDANT ACTIVITY OF N-SUBSTITUTED İNDOLE 2- AND 3-CARBOXAMIDES : N-SÜBSTİTÜE İNDOL-2 VE 3-KARBOKSAMİTLERİN ANTİOKSİDAN AKTİVİTESİ

Bir seri N-sübstitüe indol amid türevinin, sıçan karaciğerinden elde edilen mikrozomal NADP'ye bağımlı lipid peroksidasyon (LP) ve süperoksit anyon şekillenmesi üzerinde olan invitro etkileri test edildi. Vitamin E (a-tokoferol), LP seviyesini 10'4 M konsantrasyonda yaklaşık % 63 kadar azalttı. Bileşiklerden 1,8 ve 10'ün 10'4 M konsantrasyonda, a-tokoferol ile karşılaştırıldıklarında erkek karaciğer mikrozomal LP düzeylerinde belirgin bir azalmaya neden olduğu bulundu. Bileşiklerden 8 ve 10'ün, ö2(~ anyonunu belirgin bir biçimde inhibe ettiği bulundu. Her iki aktivite sonucu, bu bileşiklerin ümit verici antioksidanlar olabileceklerini gösterdi