Cardioprotective effect of telmisartan in cancer patients treated with epirubicin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20671-e20671
Author(s):  
G. Mantovani ◽  
G. Mercuro ◽  
M. Dessì ◽  
C. Madeddu ◽  
R. Serpe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Patients ◽  
Renin Angiotensin System ◽  
Myocardial Damage ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Controlled Study ◽  
Type I ◽  
Oxidative Stress Markers ◽  
Stress Markers

e20671 Background: We previously showed on 31 cancer patients (pts) that early cardiac abnormalities occurred at epirubicin (EPI) doses of 200 mg/m2 and persisted throughout subsequent EPI doses and even up to 18 months. Early contractility impairment, i.e. Strain rate (SR) reduction was detected by tissue doppler imaging (TDI) associated with high levels of inflammatory/oxidative stress markers. Renin-angiotensin system activation has been suggested to play an important role in the pathogenesis of Anthracycline-induced cardiotoxicity. Methods: A phase II placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts (50 pts per arm). Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0–2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo starting 1 week before EPI until 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline, 24 hours and 7 days at EPI doses of 100, 200, 300, and 400 mg/m2. Results: At December 2008 we enrolled 27 pts (M/F: 7/20, mean±SD age 58±14 years): 14 telmisartan and 13 placebo. 15 pts completed EPI treatment (8 telmisartan and 7 placebo). A significant reduction of SR peak was observed at 200mg/m2 of EPI in the placebo arm. Viceversa no significant TDI changes occurred in the treatment arm. Proinflammatory cytokines did not change in both arms whilst reactive oxygen species increased significantly in the placebo arm. Conclusions: The study is in progress. No significant financial relationships to disclose.

scholarly journals Glycyrrhizic acid ameliorates submandibular gland oxidative stress, autophagy and vascular dysfunction in rat model of type 1 diabetes

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Saad Mohamed Asseri ◽  
Nehal M. Elsherbiny ◽  
Mohamed El-Sherbiny ◽  
Iman O. Sherif ◽  
Alsamman M. Alsamman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Glycyrrhizic Acid ◽  
Type I Diabetes ◽  
Vascular Dysfunction ◽  
Type I ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Ameliorative Effect ◽  
Related Proteins

AbstractThe burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.

Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and myocardial dysfunction.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Giovanni Mantovani ◽  
Mariele Dessi' ◽  
Alessandra Piras ◽  
Clelia Madeddu ◽  
Laura Orgiano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Inflammation ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Renin Angiotensin System ◽  
Serum Levels ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Protective Effects ◽  
Strain And Strain Rate

9006 Background: Chronic inflammation, oxidative stress and renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, reduces anthracycline (ANT)-induced CTX. Methods: A phase II placebo (PLA)-controlled randomized trial was carried out to assess the role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were assessed. All assessments were carried out at baseline, after every 100 mg/m2 EPI dose and at 6, 12 and 18-month follow-up (FU). Results: A significant reduction in the SR peak in both arms was observed at t2 (cumulative dose of 200 mg/m2 EPI) in comparison to t0. Conversely, at t3, t4 (300, 400 mg/m2 EPI), 6, 12 and 18-month FU, the SR increased reaching the normal range only in TEL arm, while in PLA arm SR remained significantly lower as compared to t0. The differences between SR changes in PLA and TEL arms were significant from 300 mg/m2 EPI (t3) up to 18 month-FU. IL-6 increased significantly in PLA arm at t2 compared to t0, but remained unchanged in the TEL arm. ROS levels also increased significantly at t2 vs. baseline in PLA arm, while remained unchanged in TEL arm. The mean change in ROS and IL-6 at t2 was significantly different between the two arms. At 3, 6, 12 and 18 month-FU, ROS and IL-6 decreased in comparison to t2 in PLA arm, while remained low in TEL arm. Conclusions: Our results suggest that TEL is able to reverse acute EPI-induced myocardial dysfunction and maintain a normal systolic function up to 18 month-FU. These effects are likely due to two different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.

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