It is critical to detect Fe3+ and Al3+ rapidly and accurately due to their high risk to human and ecological environment. In this work, a kind of Terbium-based metal-organic framework...

Facile synthesis of fluorescent probe based on Terbium-based metal-organic framework for selective detection of Fe(III) and Al(III)

The dose-dependent cardiomyopathy of adriamycin (doxorubicin) limits its long-term clinical use, which is revealed as a consequence of cardiomyocyte ferroptosis. As a ferrous iron (Fe2+)-dependent regulated cell death pathway, ferroptosis is induced by the tailored lipid peroxides in the cell membranes. Herein, iron-chelating polymer micelles are reported for concurrent doxorubicin delivery and cardiotoxicity reduction. The amphiphilic polymer consists of methoxy poly (ethylene glycol)-co-poly (glutamic acid) copolymer as the backbone and deferiprone analog as the side chain. The chiral polymer adopted the α-helix conformation to enable prolonged retention in the cell membranes, resulting in efficient iron chelation, ferroptosis inhibition, and cardiotoxicity reduction. The co-encapsulation of doxorubicin and coenzyme Q10 (CoQ10) in micelles further alleviates the cardiotoxicity because the reduced CoQ10 can act as a radical trapping agent to constrain lipid peroxidation and cardiomyocyte ferroptosis. The reduction of cardiotoxicity is accompanied by enhanced anticancer efficacy in an in vivo murine breast cancer model. The chiral iron-chelating polymer micelles can be a promising platform for enhanced doxorubicin delivery and reduced cardiac adverse effects. 

Chiral Polymer Micelles Alleviate Adriamycin Cardiotoxicity via Iron Chelation and Ferroptosis Inhibition

Abstract Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPATROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. EMPATROPISM-FE explored post hoc in this cohort, who had a high prevalence of iron deficiency, whether treatment effects were related to changes in iron metabolism. Here we show that myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin, but not placebo (between-group difference p = 0.01). T2* changes were significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Our findings suggest that effects of empagliflozin on iron metabolism may be a potential mechanism mediating its beneficial clinical effects in patients with HF. Clinical Trial Registration: www.clinicaltrials.gov; NCT03485222 

/pdf/empagliflozin-effects-on-iron-metabolism-as-a-possible-156xack3.pdf

Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure

Oxidative stress is an important mechanism of myocardial damage during ischemia/reperfusion. To investigate the possibility of restoring the redox balance using “indirect” antioxidant effects, the cardioprotective effect Keap1/Nrf2/ ARE system inducers was studied in long-term ischemia/reperfusion in vivo. Material and methods. We used the original synthetic hydrophilic monophenol sodium 3-(3’-tert-butyl-4’-hydroxyphenyl) propyl thiosulfonate (TS-13) and reference drug tert-butylhydroquinone (tBHQ). Male Wistar rats received 100 mg/kg of TS-13 solution (with drinking water) or tBHQ (intraperitoneally) daily for 7 days. Animals of the comparison groups received the corresponding solvents. Local ischemia (45 min, occlusion of the left coronary artery) and reperfusion (120 min) of the heart were simulated in vivo 1 day after last drug administration. The ECG was recorded during ischemia and reperfusion; at the end of reperfusion, the heart was removed, the zone of hypoperfusion and the zone of necrosis were detected. Changes in the expression of the mRNA of Nfe2l2, Nqo1, Hmox1, Gstp1, Rela, and Nfkb2 gene in myocardial tissue were determined by real-time TaqMan PCR. Results and discussion. Pretreatment with TS-13 and tBHQ did not influence the infarct size and the incidence of ventricular arrhythmias. Preliminary administration of tBHQ did not change the genes expression of the studied in myocardial tissue after prolonged I/R. TS-13 administration was accompanied by an increase in the content of the transcripts of the gene that encodes Nrf2 (by 7.64 times) and Nrf2-driven genes Nqo1 (by 6.46 times) and Hmox1 (by 3.63 times); the expression of the Gstp1, Rela, and Nfkb2 genes did not differ from the corresponding values of the control group; compared to animals treated with tBHQ, the expression of the Nfe2l2, Nqo1, Hmox1, Rela, and Nfkb2 genes was 16.23, 4.44, 2.68, 3.17, and 2.64 times higher, respectively. The results obtained cast doubt on the therapeutic importance of the induction of the Keap1/Nrf2/ARE system during prolonged heart ischemia/reperfusion.

Kishore Kumar S. Narasimhan

Papers

Triad role of hepcidin, ferroportin, and Nrf2 in cardiac iron metabolism: From health to disease.