Disruption of iron homeostasis increases phosphine toxicity in caenorhabditis elegans

The aim of this study is to identify the biochemical mechanism of phosphine toxicity and resistance, using Caenorhabditis elegans as a model organism. To date, the precise mode of phosphine action is unclear. In this report, we demonstrate the following dose-dependent actions of phosphine, in vitro: (1) reduction of ferric iron (Fe3+) to ferrous iron (Fe2+), (2) release of iron from horse ferritin, (3) and the peroxidation of lipid as a result of iron release from ferritin. Using in situ hybridization, we show that the ferritin genes of C. elegans, both ferritin-1 and ferritin-2, are expressed along the digestive tract with greatest expression at the proximal and distal ends. Basal expression of the ferritin-2 gene, as determined by quantitative PCR, is approximately 80 times that of ferritin-1. However, transcript levels of ferritin-1 are induced at least 20-fold in response to phosphine, whereas there is no change in the level of ferritin-2. This resembles the reported pattern of ferritin gene regulation by iron, suggesting that phosphine toxicity may be related to an increase in the level of free iron. Indeed, iron overload increases phosphine toxicity in C. elegans at least threefold. Moreover, we demonstrate that suppression of ferritin-2 gene expression by RNAi, significantly increases sensitivity to phosphine. This study identifies similarities between phosphine toxicity and iron overload and demonstrates that phosphine can trigger iron release from storage proteins, increasing lipid peroxidation, leading to cell injury and/or cell death.

Urinary excretion of antioxidants in healthy humans following queen garnet plum juice ingestion: a new plum variety rich in antioxidant compounds

In recent years, there has been intense interest in the potential health benefits of dietary derived plant polyphenols and antioxidants. A new variety of Prunus salicina, Queen Garnet plum (QGP), was developed as a high anthocyanin, high antioxidant plum, in a Queensland Government breeding program. Following consumption of 400 mL QGP juice (QGPJ; 1,117 mg anthocyanins) by two healthy male subjects, QGP anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside) were excreted mainly as methylated and glucuronidated metabolites in urine (0.5% of the ingested dose within 24 h). Furthermore, QGPJ intake resulted in a threefold increase in hippuric acid excretion (potential biomarker for total polyphenols intake and metabolite), an increased urinary antioxidant capacity and a decreased malondialdehyde excretion (biomarker for oxidative stress) within 24 h as compared with the polyphenol-/antioxidant-free control. Results from this pilot study suggest that metabolites, and not the native QGP anthocyanins/polyphenols, are most likely the bioactive compounds in vivo.

Increasing anthocyanin content in Queen Garnet plum and correlations with in-field measures

While plums are traditionally bred for fresh fruit traits such as size, sweetness, yield and disease resistance the Queensland Government breeding program for Japanese plum ( Prunus salicina Lindl.) also selected for anthocyanin content to develop a new plum selection named 'Queen Garnet'. When ripe or overripe, it has a near black skin and deep red flesh colour, which when combined, result in exceptionally high anthocyanin content, reaching up to 277 mg/100 g fruit. The skin fraction contributes 36-66% of the total anthocyanin content of fruit. The plum is now being commercially grown to be processed into a range of functional products from food colourants to premium health products. These are sold on the basis of anthocyanin and antioxidant content. Protocols for increasing anthocyanin content have therefore been researched to maximise the total anthocyanin yield rather than fresh fruit weight and taste. The principal approach is through selective harvest of overripe plums high in colour, although post-harvest storage at 21°C results in further anthocyanin synthesis. Modified processing is also required to ensure recovery of anthocyanins from the skin fraction. The plum products have entered testing for assessing health properties beginning with an initial proof of in vivo bioavailability of the anthocyanins.

Consumption of anthocyanin-rich Queen Garnet plum juice reduces platelet activation related thrombogenesis in healthy volunteers

The anti-thrombotic properties of an anthocyanin-rich Queen Garnet plum juice (QGPJ) and anthocyanin-free prune juice (PJ) were studied in this randomised, double-blind, crossover trial. Twenty-one healthy subjects (M = 10, F = 11) consumed QGPJ, PJ or placebo, 200 mL/day for 28-days followed by a 2-week wash-out period. Only QGPJ supplementation inhibited platelet aggregation induced by ADP (<5%, P = 0.02), collagen (<2.7%, P < 0.001) and arachidonic acid (<4%, P < 0.001); reduced platelet activation-dependent surface-marker P-selectin expression of activated de-granulated platelets (<17.2%, P = 0.04); prolonged activated-partial thromboplastin clotting time (>2.1 s, P = 0.03); reduced plasma-fibrinogen (<7.5%, P = 0.02) and malondialdehyde levels, a plasma biomarker of oxidative stress ( P = 0.016). PJ supplementation increased plasma hippuric acid content ( P = 0.018). QGPJ or PJ supplementation did not affect blood cell counts, lipid profile, or inflammation markers. Our findings suggest that QGPJ but not PJ has the potential to significantly attenuate thrombosis by reducing platelet activation/hyper-coagulability and oxidative stress.