Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse cardiac remodeling in diabetic animals.

Abstract

Diabetic cancer patients were treated with doxorubicin (DOX), a potent chemotherapeutic drug that induces cardiac toxicity; however, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of DOX-induced cardiac toxicity in diabetic animals and the involved pathophysiological mechanisms. C57BL/6 J mice were divided into four DOX- and diabetic (streptozotocin; STZ) - treated groups; control, STZ, DOX, and DOX+STZ. At day 14, animals were sacrificed, echocardiography was used to examine heart function, and heart and blood samples were collected to investigate apoptotic mechanisms (caspase 3, BAX, B-Cell leukemia/lymphoma 2 (Bcl2)), inflammation, and cardiac remodeling. Our data shows a significant (p < 0.05) increase in glucose levels, apoptotic markers, and monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)), in DOX+STZ animals compared with control and experimental groups. We also observed significant (p < 0.05) increase in myofibrillar area, fibrosis, and significantly decreased (p < 0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX induces significantly increased apoptosis, fibrosis, and structural alterations in diabetic hearts compared with non-diabetic animals.

• Authors: Chandrakala Aluganti Narasimhulu, Dinender K Singla
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 100 Issue 5 Pg. 441-452 (May 2022) ISSN: 1205-7541 [Electronic] Canada
• PMID: 34932406 (Publication Type: Journal Article)

Chemical References

• Streptozocin
• Doxorubicin

Topics

• Animals
• Apoptosis
• Cardiotoxicity
• Diabetes Mellitus
• Doxorubicin (adverse effects)
• Fibrosis
• Humans
• Mice
• Mice, Inbred C57BL
• Monocytes
• Streptozocin (pharmacology)
• Ventricular Remodeling