Krebs Cycle Intermediates Modulate Thiobarbituric Acid Reactive Species (TBARS) Production in Rat Brain In Vitro

Abstract

The aim of this study was to investigate the effect of Krebs cycle intermediates on basal and quinolinic acid (QA)- or iron-induced TBARS production in brain membranes. Oxaloacetate, citrate, succinate and malate reduced significantly the basal and QA-induced TBARS production. The potency for basal TBARS inhibition was in the order (IC50 is given in parenthesis as mM) citrate (0.37) > oxaloacetate (1.33) = succinate (1.91) > > malate (12.74). alpha-Ketoglutarate caused an increase in TBARS production without modifying the QA-induced TBARS production. Cyanide (CN-) did not modify the basal or QA-induced TBARS production; however, CN- abolished the antioxidant effects of succinate. QA-induced TBARS production was enhanced by iron ions, and abolished by desferrioxamine (DFO). The intermediates used in this study, except for alpha-ketoglutarate, prevented iron-induced TBARS production. Oxaloacetate, citrate, alpha-ketoglutarate and malate, but no succinate and QA, exhibited significantly iron-chelating properties. Only alpha-ketoglutarate and oxaloacetate protected against hydrogen peroxide-induced deoxyribose degradation, while succinate and malate showed a modest effect against Fe2+/H2O2-induced deoxyribose degradation. Using heat-treated preparations citrate, malate and oxaloacetate protected against basal or QA-induced TBARS production, whereas alpha-ketoglutarate induced TBARS production. Succinate did not offer protection against basal or QA-induced TBARS production. These results suggest that oxaloacetate, malate, succinate, and citrate are effective antioxidants against basal and iron or QA-induced TBARS production, while alpha-ketoglutarate stimulates TBARS production. The mechanism through which Krebs cycle intermediates offer protection against TBARS production is distinct depending on the intermediate used. Thus, under pathological conditions such as ischemia, where citrate concentrations vary it can assume an important role as a modulator of oxidative stress associated with such situations.

Characterization of the antioxidant properties of phenolic extracts from some citrus peels

“…Nevertheless, the phenolic extracts significantly (P<0.05) inhibited MDA production in the pancreas in a dose-dependent manner, bound phenolics from orange and shaddock peels had the highest inhibitory effect on MDA production in the pancreas (in vitro), while bound phenolics from grapefruit peels had the least inhibitory effect ( Table 2). The possible mechanism through which the phenolic extracts protect the pancreas could be by Fe 2+ chelation (Oboh and Rocha 2007a, b) and the scavenging of OH* (Puntel et al 2005;Oboh and Rocha 2007a, b). Since the phenolic extracts had higher Fe 2+ chelating ability than OH* scavenging ability, Fe 2+ chelation could be the domineering mechanism through which the phenolics protect the pancreas membrane from Fe 2+ induced lipid peroxidation in pancreas.…”

In vitro inhibition activity of polyphenol-rich extracts from Syzygium aromaticum (L.) Merr. & Perry (Clove) buds against carbohydrate hydrolyzing enzymes linked to type 2 diabetes and Fe2+-induced lipid peroxidation in rat pancreas

“…Furthermore Lipid peroxidation in biological membranes is considered as one of the major mechanisms of cell injury in aerobic organisms subjected to oxidative stress [13] . The chain reaction of lipid peroxidation ensures continuous supply of free radicals which initiate further peroxidation [13,47] . Recent report suggests that iron accumulation contributes to increased free radical formation and oxidative stress.…”

Drying alters the phenolic constituents, antioxidant properties, α‐amylase, and α‐glucosidase inhibitory properties of Moringa (Moringa oleifera) leaf

“…The hydroxyl radical ( • OH) scavenging assay was based on the ability of the extracts to scavenge/prevent • OH production from Fe 2+ /H 2 O 2 ‐induced decomposition of deoxyribose in solution. The Fe 2+ chelating ability of the extracts was determined using a modified method of Minotti and Aust (1987) with a slight modification by Puntel, Nogueira, and Rocha (2005). Furthermore, the ability of the extracts to prevent both FeSO 4 and sodium nitroprusside‐induced lipid peroxidation in rat's pancreas and liver homogenates was studied (Ohkawa, Ohishi, & Yagi, 1979).…”