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Homeostasis rescue: the effect of drug vs lifestyle approach in low dose of doxorubicin treated rats
Session:
CO 05 - Ciência Básica
Speaker:
Filipa Machado
Congress:
CPC 2021
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.2 Basic Science - Cardiac Biology and Physiology
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Filipa Machado; Ângela Amaro-Leal; Ana i. Afonso; isabel rocha; Vera Geraldes
Abstract
<p style="text-align:justify">Doxorubicin (DOX) is a highly effective anticancer agent that improved survival and patient’s quality of live but causes dose-dependent cardiotoxic effects leading to a severe and irreversible cardiomyopathy in many patients. Different preventive strategies, such physical exercise and β-blockers, have been proposed to maintain the physiological homeostasis. However, besides the extensive research has been done to understand the mechanism and pathophysiology of DOX it is not clear what is the most effective preventive approach to maintain the physiological homeostasis. </p> <p style="text-align:justify">In the present work, we intended to compare the efficacy of two different approaches, one pharmacological intervention, using atenolol, a β1 selective antagonist without antioxidant properties, and other non-pharmacological intervention using a treadmill training in an animal model of DOX. Female Wistar rats were divided into 4 groups: Doxorubicin (DOX; ip. cumulative dose 8 mg/kg, 1 time/week, for 4 weeks), DOX with physical exercise (DOX + EX; treadmill, 22 cm/seg for 30 minutes, 5 times/week), DOX with β-blocker (DOX + ATN: DOX; ip. cumulative dose 8 mg/kg, 1 time/week and 4 mg/ml, Atenolol; oral administration, 5 times/week, for 4 weeks) and controls (ip. with saline solution). Blood pressure (BP), cardiac (HR) and respiratory (RF) frequency, baro- and chemoreflexes were evaluated.</p> <p style="text-align:justify">Our results reveal that DOX treatment triggered a significant decrease in BP and HR, caused hypopnea, decreased baro and chemoreflexes, without evidence of sympatho-excitation. These changes can be explained by the decline in cardiac function, respiratory muscle weakness, autonomic dysfunction and vascular changes induces by low doses of DOX. During treatment with DOX, the physical activity protocol countered some of the adverse effects caused by DOX. It normalized BP, HR and RF to physiological values, and decreases the loss in baroreflex gain. Chemoreflex sensitivity, sympathetic and parasympathetic activities remained similar. Atenolol treatment, similar to physical activity effect, also increased baroreflex gain and RF to normal values, causing also a clear tendency to maintain BP values.</p> <p style="text-align:justify">Although complementary data is still needed, with these results we can conclude that treadmill training was more effective than atenolol in counteracting the adverse effects of the cumulative low dose of DOX administered, suggesting that physical activity is a good non-pharmacological alternative to atenolol for preserving the homeostasis during DOX therapy. </p>
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