cyanidin-3-o-beta-glucopyranoside and Reperfusion-Injury

Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway.. Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined.. We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro.. Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.

Topics: Acute Kidney Injury; AMP-Activated Protein Kinases; Animals; Ferroptosis; Iron; Ischemia; Lipids; Mice; Reactive Oxygen Species; Reperfusion Injury

Our previous research showed the antioxidant activity of anthocyanins extracted from. Acute renal injury model was initiated by 30 min clamping bilateral renal pedicle and followed by 24-hour reperfusion in C57Bl/6J mice. Four groups of mice were orally pretreated in 50 mg/g/12 h for two weeks with cyanidin-3-arabinoside, cyanidin-3-glucodise, and cyaniding-3-galactoside and anthocyanins (three-cyanidin mixture), respectively, sham-control group and the renal injury-untreated groups only with saline.. The model resulted in renal dysfunction with high serum creatinine, blood urea nitrogen, and changes in proinflammatory cytokines (TNF-ɑ, IL-1. the current study provided the first attempt to investigate the role of anthocyanins purified from

Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Arabinonucleosides; Body Weight; Caspase 9; Fruit; Galactosides; Inflammation; Kidney; Kidney Failure, Chronic; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Oxidative Stress; Photinia; Reperfusion; Reperfusion Injury; Risk

It is well known that cardiomyocyte apoptosis contributes to ischemic heart damage. There is also increasing evidence that the polyphenolic compounds of natural origin, such as anthocyanins, may attenuate ischemia/reperfusion injury though the mechanisms of such protection are not clear. Following our previous studies showing the effect of certain anthocyanins on cytochrome c redox state, mitochondrial functions, and ischemia-induced caspase activation in the heart, here we investigated whether these anthocyanins can rescue cardiac cells from death by the mechanism involving the reduction of cytosolic cytochrome c.. Before global ischemia and reperfusion, isolated rat hearts were preloaded with cyanidin-3-O-glucoside (Cy3G) that has high cytochrome c-reducing capacity or pelargonidin-3-O-glucoside (Pg3G) that possesses low reducing activity. Cell death was evaluated assessing apoptosis by the TUNEL method or necrosis measuring the release of lactate dehydrogenase into perfusate.. The perfusion of hearts with 20-μM Cy3G prevented ischemia/reperfusion-induced apoptosis of cardiomyocytes: the number of TUNEL-positive myocytes was decreased by 73% if compared with the untreated ischemic group. The same effect was observed measuring the activity of lactate dehydrogenase as the measure of necrosis: perfusion with 20-μM Cy3G reduced the level of LDH release into the perfusate to the control level. The perfusion of hearts with 20-μM Pg3G did not prevent ischemia/reperfusion-induced apoptosis as well as necrosis.. Cy3G protected the rat heart from ischemia/reperfusion-induced apoptosis and necrosis; meanwhile, Pg3G did not exert any protective effect. The protective effect of Cy3G may be related due to its high capacity to reduce cytosolic cytochrome c.

Topics: Animals; Anthocyanins; Apoptosis; Cytochromes c; Cytoprotection; Glucosides; Male; Myocardial Ischemia; Myocytes, Cardiac; Necrosis; Rats; Rats, Wistar; Reperfusion Injury

Topics: Anesthetics; Animals; Anthocyanins; Antioxidants; Carbon Monoxide; Curcumin; Cytoprotection; Disease Models, Animal; Flavonoids; Glucosides; Heme Oxygenase-1; Hepatocytes; Humans; Isoflurane; Liver; Liver Diseases; Liver Transplantation; Phenols; Polyphenols; Propofol; Reperfusion Injury

The cyanidin-3-O-beta-glucopyranoside (C-3-G) antioxidant capacity towards reactive oxygen species (ROS)-mediated damages was assessed in tissue and cells submitted to increased oxidative stress. In the isolated ischemic and reperfused rat heart, 10 or 30 degreesM C-3-G protected from both lipid peroxidation (66.7 and 94% inhibition of malondialdehyde (MDA) generation in 10 and 30 microM C-3-G-reperfused hearts, respectively, in comparison with control reperfused hearts) and energy metabolism impairment (higher ATP concentration in 10 and 30 microM C-3-G-reperfused hearts than in control reperfused hearts). These effects were associated to C-3-G permeation within myocardial cells, as indicated by results obtained in the isolated rat heart perfused for 30 min in the recirculating Langendorff mode under normoxia with 10 and 30 microM C-3-G. Protective effects were exerted, in a dose-dependent manner, by C-3-G also in 2 mM hydrogen peroxide-treated human erythrocytes. With respect to MDA formation, an apparent IC50 of 5.12 microM was calculated for C-3-G (the polyphenol resveratrol used for comparison showed an apparent IC50 of 38.43 microM). The general indications are that C-3-G (largely diffused in dietary plants and fruits, such as pigmented oranges very common in the Mediterranean diet) represents a powerful natural antioxidant with beneficial effects in case of increased oxidative stress, and at pharmacological concentrations it is able to decrease tissue damages occurring in myocardial ischemia and reperfusion.

Topics: Adenosine Triphosphate; Animals; Anthocyanins; Antioxidants; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Erythrocytes; Free Radicals; Inhibitory Concentration 50; Male; Myocardium; Oxidative Stress; Oxygen; Perfusion; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Time Factors

We have shown that the orally administered cyanidin 3-O-beta-D-glucoside (C3G) attenuates the hepatic ischemia-reperfusion (I/R) injury, which was used as a model for oxidative stress through a decrease in neutrophil chemoattractant production in rats. The rats were subjected to hepatic I/R at 30 min after the administration of C3G (0.9 mmol/kg body weight) or vehicle. I/R treatment resulted in the elevation of oxidative stress marker [liver thiobarbituric acid-reactive substance, Nepsilon-(hexanonyl) lysine and dityrosine] levels in the liver and of the serum activities of marker enzymes for liver injury. The administration of C3G significantly suppressed these elevations, which had been caused by hepatic I/R. Liver myeloperoxidase activity, a useful marker for neutrophil infiltration into tissues, and the plasma and liver concentration of cytokine-induced neutrophil chemoattractant-1 (CINC-1), which has a potent chemotactic activity, were markedly elevated in the control group after hepatic I/R. However, these elevations were significantly suppressed in the C3G group. C3G and its metabolites in the plasma and liver were detected in the C3G group after hepatic I/R. These results suggest that the absorbed C3G and/or its metabolites can act as antioxidants in the blood and liver and scavenge the reactive oxygen species, and brought on a decrease in neutrophil infiltration into the liver through the suppression of CINC-1 production and the tissue damage caused by neutrophils after I/R is attenuated.

Topics: Animals; Anthocyanins; Antioxidants; Biomarkers; Chemotactic Factors; Glucosides; Liver; Male; Neutrophils; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Thiobarbituric Acid Reactive Substances

Cyanidin 3-O-beta-D-glucoside (C3G) is included in anthocyanins, and expected to have a potency to scavenge active oxygen species in vivo. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days, and then subjected to hepatic ischemia-reperfusion (I/R) as an oxidative stress model. I/R treatment elevated the liver thiobarbituric acid-reactive substance concentration and the serum activities of marker enzymes for liver injury, and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. These results indicate that C3G functions as a potent antioxidant in vivo under oxidative stress. To clarify the mechanism of action of C3G, we investigated the absorption and metabolism of C3G in rats. C3G appeared in the plasma immediately after the oral administration of C3G. Protocatechuic acid, which seems to be produced by the degradation of cyanidin, was also present in the plasma. In the liver and kidneys, C3G was metabolized to methylated form.

Topics: Animals; Anthocyanins; Antioxidants; Biotransformation; Glucosides; Intestinal Absorption; Ischemia; Kidney; Lipid Peroxidation; Liver; Male; Models, Biological; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Thiobarbituric Acid Reactive Substances

We recently reported that feeding cyanidin 3-O-beta-d-glucoside (C3G), a typical anthocyanin pigment, lowered the serum thiobarbituric acid-reactive substance (TBARS) concentration and increased the oxidation resistance of the serum to lipid peroxidation in rats. These results suggest that C3G acts as a potent antioxidant in vivo when acute oxidative stress is encountered. In the present study, we evaluated whether feeding C3G suppresses oxidative injury to the liver caused by hepatic ischemia-reperfusion (I/R), which was used as a model for oxidative stress. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days and then subjected to hepatic I/R. I/R treatment elevated the liver TBARS concentration and the serum activities of marker enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase) for liver injury and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. Although the liver ascorbic acid concentration was also lowered by hepatic I/R, feeding C3G restored this concentration more quickly compared to the control rats. These results indicate that orally administered C3G suppresses I/R-induced oxidative damage and suggest that C3G functions as a potent antioxidant in vivo under oxidative stress.

Topics: Animals; Anthocyanins; Antioxidants; Glucosides; Ischemia; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Reperfusion Injury