Sonata Trumbeckaite

The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.

Crataegus (Hawthorn) fruit extracts (CE) are widely used for the treatment of various cardiovascular diseases (arrhythmias, heart failure, myocardial weakness, etc). Despite the fact that many of these diseases are associated with disturbances of the mitochondria, no data have been found on the effect of CE on their function. The aim of this study was to perform an oxygraphic investigation of the effect of CE (in concentration range from 70 ng/mL to 13.9 µg/mL of Crataegus phenolic compounds (PC)) and its several pure flavonoids on isolated rat heart mitochondria respiring on pyruvate + malate, succinate and palmitoyl‐L‐carnitine + malate. CE at doses under 278 ng/mL of PC had no effect on mitochondrial functions. At concentrations from 278 ng/mL to 13.9 µg/mL of PC, CE stimulated State 2 respiration by 11%–34% with all used substrates, and decreased the mitochondrial membrane potential by 1.2–4.4 mV measured with a tetraphenylphosphonium‐selective electrode and H2O2 production measured fluorimetrically. Similar uncoupling effects on mitochondrial respiration were observed with several pure CE flavonoids. The highest CE concentration also slightly reduced the maximal ADP‐stimulated and uncoupled respiration, which might be due to inhibition of the mitochondrial respiratory chain between flavoprotein and cytochrome c. Whether or not the uncoupling and other effects of CE on mitochondria may be realized in vivo remains to be determined. Copyright

Anthocyanins block ischemia-induced apoptosis in the perfused heart and support mitochondrial respiration potentially by reducing cytosolic cytochrome c.

Anthocynanins, found in fruits and vegetables, have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, antioxidants are generally strong reductants, and some reductants have been found to block apoptosis by reducing cytosolic cytochrome c, which prevents caspase activation. We tested the ability of various anthocyanins: to reduce cytochrome c, to support cytochrome c-induced mitochondrial respiration and to inhibit apoptosis induced by heart ischemia. Anthocyanins such as delphinidin-3-glucoside (Dp3G) and cyanidin-3-glucoside (Cy3G) were able to reduce cytochrome c directly and rapidly, whereas pelargonidin-3-glucoside (Pg3G), malvinidin-3-glucoside (Mv3G) and peonidin-3-glucoside (Pn3G) had relatively low cytochrome c reducing activities. Dp3G and Cy3G but not Pg3G supported mitochondrial state 4 respiration in the presence of exogenous cytochrome c. Pre-perfusion of hearts with 20 μM Cy3G but not Pg3G prevented ischemia-induced caspase activation. This suggests that the ability of anthocyanins to block caspase activation may be due to their ability to reduce cytosolic cytochrome c. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Anthocyanins in cardioprotection: A path through mitochondria

Constantly growing experimental data from in vitro, in vivo and epidemiological studies show the great potential of anthocyanin-containing fruit and berry extracts or pure individual anthocyanins as cardioprotective food components or pharmacological compounds. In general it is regarded that the cardioprotective activity of anthocyanins is related to their antioxidant properties. However there are recent reports that certain anthocyanins may protect the heart against ischemia/reperfusion-induced injury by activating signal transduction pathways and sustaining mitochondrial functions instead of acting solely as antioxidants. In this review, we summarize the proposed mechanisms of direct or indirect actions of anthocyanins within cardiac cells with the special emphasis on recently discovered their pharmacological effects on mitochondria in cardioprotection: reduction of cytosolic cytochrome c preventing apoptosis and sustainment of electron transfer between NADH dehydrogenase and cytochrome c supporting oxidative phosphorylation in ischemia-damaged mitochondria.

Oxygen glucose deprivation causes mitochondrial dysfunction in cultivated rat hippocampal slices: Protective effects of CsA, its immunosuppressive congener [D-Ser]8CsA, the novel non-immunosuppressive cyclosporin derivative Cs9, and the NMDA receptor antagonist MK 801

We have introduced a sensitive method for studying oxygen/glucose deprivation (OGD)-induced mitochondrial alterations in homogenates of organotypic hippocampal slice cultures (slices) by high-resolution respirometry. Using this approach, we tested the neuroprotective potential of the novel non-immunosuppressive cyclosporin (CsA) derivative Cs9 in comparison with CsA, the immunosuppressive CsA analog [D-Ser](8)CsA, and MK 801, a N-methyl-d-aspartate (NMDA) receptor antagonist. OGD/reperfusion reduced the glutamate/malate dependent (and protein-related) state 3 respiration to 30% of its value under control conditions. All of the above drugs reversed this effect, with an increase to >88% of the value for control slices not exposed to OGD. We conclude that Cs9, [D-Ser](8)CsA, and MK 801, despite their different modes of action, protect mitochondria from OGD-induced damage.

Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis

The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats.

Effects of Cyanidin-3-O-glucoside on Synthetic and Metabolic Activity of Ethanol Stimulated Human Pancreatic Stellate Cells

Activated pancreatic stellate cells (PSC) play a major role in the development of chronic pancreatitis. Flavonoids (C‐3‐O‐G) theoretically may have potential to suppress activated PSC. The aim of our study was to determine the ability of C‐3‐O‐G to invert synthetic and metabolic activity of alcohol stimulated human pancreatic stellate cells (hPSC). In the present study we demonstrate that treatment with C‐3‐O‐G decreased proliferation rate of ethanol activated hPSC by 51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly inhibited, as shown by reduced levels of collagen I and fibronectin expression. The decrease of secretion of fibronectin by 33% and in collagen I‐25% in ethanol activated and C‐3‐O‐G treated hPSC was observed. Moreover, treatment of ethanol activated hPSC with C‐3‐O‐G resulted in the decrease of oxygen consumption rate by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%. Hence, the effects of C‐3‐O‐G on ethanol activated hPSC may provide new insights for the use of anthocyanins as anti‐fibrogenic agents in treatment and/or prevention of pancreatic fibrosis. Copyright