ABSTRACT

AIMS: Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies.

METHODS: We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed.

RESULTS: Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95%CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95%CI: 0.62-0.82, p<0.0001),<0.0001),<0.0001),

CONCLUSIONS: This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.

PMID:37257759 | DOI:10.1016/j.diabres.2023.110734

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PubMed articles on: Cardio-Oncology

AKR1B1 inhibition using NARI-29-an Epalrestat analogue-alleviates Doxorubicin-induced cardiotoxicity via modulating Calcium/CaMKII/MuRF-1 axis

Chem Biol Interact. 2023 May 29:110566. doi: 10.1016/j.cbi.2023.110566. Online ahead of print.

ABSTRACT

The clinical use of doxorubicin (Dox) is narrowed due to its carbonyl reduction to doxorubicinol (Doxol) implicating resistance and cardiotoxicity. Hence, in the present study we have evaluated the cardioprotective effect of AKR1B1 (or aldose reductase, AR) inhibitor NARI-29 (epalrestat (EPS) analogue) and its effect in the Dox-modulated calcium/CaMKII/MuRF1 axis. Initially, the breast cancer patient survival associated with AKR1B1 expression was calculated using Kaplan Meier-plotter (KM-plotter). Further, breast cancer, cardiomyoblast (H9c2), and macrophage (RAW 264.7) cell lines were used to establish the in vitro combination effect of NARI-29 and Dox. To develop the cardiotoxicity model, mice were given Dox 2.5 mg/kg (i.p.), biweekly. The effect of AKR1B1 inhibition using NARI-29 on molecular and cardiac functional changes was measured using echocardiography, fluorescence-imaging, ELISA, immunoblotting, flowcytometry, High-Performance Liquid Chromatography with Fluorescence Detection (HPLC-FD) and cytokine-bead array methods. The bioinformatics data suggested that a high expression of AKR1B1 is associated with significantly low survival of breast cancer patients undergoing chemotherapy; hence, it could be a target for chemo-sensitization and chemo-prevention. Further, in vitro studies showed that AKR1B1 inhibition with NARI-29 has increased the accumulation and sensitized Dox to breast cancer cell lines. However, treatment with NARI-29 has alleviated the Dox-induced toxicity to cardiomyocytes and decreased the secretion of inflammatory cytokines from RAW 264.7 cells. In vivo studies revealed that the NARI-29 (25 and 50 mg/kg) has prevented the functional, histological, biochemical, and molecular alterations induced by Dox treatment. Moreover, we have shown that NARI-29 has prevented the carbonyl reduction of Dox to Doxol in the mouse heart, which reduced the calcium overload, prevented phosphorylation of CaMKII, and reduced the expression of MuRF1 to protect from cardiac injury and apoptosis. Hence in conclusion, AKR1B1 inhibitor NARI-29 could be used as an adjuvant therapeutic agent with Dox to prevent cardiotoxicity and synergize anti-breast cancer activity.

PMID:37257577 | DOI:10.1016/j.cbi.2023.110566

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PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

Anatol J Cardiol. 2023 Jun;27(6):298. doi: 10.14744/AnatolJCardiol.2023.6.

NO ABSTRACT

PMID:37257014 | DOI:10.14744/AnatolJCardiol.2023.6

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PubMed articles on: Cardio-Oncology

Cancer Therapy-Related Pulmonary Hypertension: A Review of Mechanisms and Implications for Clinical Practice

Anatol J Cardiol. 2023 Jun;27(6):299-307. doi: 10.14744/AnatolJCardiol.2023.3013.

ABSTRACT

Cancer therapy-related pulmonary hypertension is a rare yet potentially fatal cardiotoxicity. However, it is a reversible cause of pulmonary hypertension if detected in its early stages. Cancer therapy-related pulmonary hypertension has been encountered in patients using tyrosine kinase inhibitors, particularly dasatinib. However, it is also well known that many agents used in cancer treatment such as alkylating agents, proteasome inhibitors, thoracic radiation exposure, and immune checkpoint inhibitors are particularly associated with pulmonary hypertension evolution. In case that history, symptoms, and clinical findings suggest a potential cancer therapy-related pulmonary hypertension, echocardiography is considered as the initial tool to detect pulmonary hypertension. If the possibility of pulmonary hypertension is high based on echocardiographic data, cancer treatment, as the initial step, should be discontinued due to its potential risks and other causes for pulmonary hypertension should be investigated thoroughly. Right heart catheterization should be the next step to establish the final diagnosis, and medical management, where appropriate, should be started without delay in these patients according to their pulmonary hypertension subgroup. There exists limited information regarding the diagnostic and management strategies of cancer therapy-related pulmonary hypertension in the current guidelines. In this review article, we aim to present current literature data on the mechanisms and management of cancer therapy-related pulmonary hypertension along with its follow-up algorithm in the setting of cardio-oncology practice.

PMID:37257013 | DOI:10.14744/AnatolJCardiol.2023.3013

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PubMed articles on: Cardio-Oncology

Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity

Anatol J Cardiol. 2023 Jun;27(6):339-347. doi: 10.14744/AnatolJCardiol.2023.2825.

ABSTRACT

BACKGROUND: Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity.

METHODS: A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity.

RESULTS: Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group.

CONCLUSION: Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.

PMID:37257007 | DOI:10.14744/AnatolJCardiol.2023.2825

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PubMed articles on: Cardio-Oncology

Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer

JAMA Cardiol. 2023 May 31. doi: 10.1001/jamacardio.2023.1229. Online ahead of print.