Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats

Abstract

Aim: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. Methods: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. Results: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. Conclusion: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.

Lady’s Bedstraw as a Powerful Antioxidant for Attenuation of Doxorubicin-Induced Cardiotoxicity

“…Additionally, the lusitropic property of the heart was also diminished, as manifested by the drop in dp/dt min values, as well as the systolic and diastolic heart capacities. The abovementioned results are in line with the literature data referring to the doxorubicin-induced functional dysfunction [ 22 , 23 ]. The investigations pointed to a few mechanisms for cardiac dysfunction provoked by DOX, such as increased production of ROS leading to oxidative stress damage, disrupted Ca 2+ homeostasis, and impaired genes’ expression involved in the apoptosis and necrosis of cardiomyocates [ 24 , 25 ].…”

Cardiovascular Toxicity Related to Cancer Treatment

“…Dantas et al investigated the influence of doxycycline (an anti-inflammatory and matrix metalloproteinase inhibitor) on the attenuation of doxorubicin induced cardiotoxicity, in 80 male Wistar rats (group A: control, group B: doxorubicin, group C: doxycycline and group D: doxorubicin + doxycycline) [ 11 ]. The researchers observed an increase in the activity of enzymes associated with glucose metabolism and a decrease in the activity of enzymes related to lipid metabolism (which characterizes cardiac injury) in the doxorubicin group.…”