Involvement of TRPM2 Channel on Doxorubicin-Induced Experimental Cardiotoxicity Model: Protective Role of Selenium.

Abstract

Doxorubicin (DOXR) is an important chemotherapeutic drug used in cancer treatment for many years. Several studies reported that the use of DOXR increased toxicity by causing an increase in oxidative stress (OS), especially in the heart. In this study, we investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation by using N-(p-amylcinnamoyl) anthranilic acid (ACA) in a model of DOXR-induced cardiotoxicity. Sixty female rats were equally divided into the control, dimethyl sulfoxide (DMSO), DOXR, DOXR + Se, DOXR + ACA, and DOXR + Se + ACA groups. Glutathione (GSH), glutathione peroxidase (GSH-Px), caspases (Cas) 3 and 9, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP-1), and TRPM2 channel levels were measured by ELISA. In addition, histopathological examination was performed in cardiac tissues and TNF-α, caspase 3, and TRPM2 channel expression levels were determined immunohistochemically. The levels of GSH, GSH-Px, caspases 3 and 9, IL-1β, TNF-α, ROS, PARP-1, and TRPM2 channel in serum, and cardiac tissue in the DOXR group were higher than in the control and DMSO groups (p < 0.05). However, these parameters in Se and/or ACA treatment groups were lower than in the DOXR group (p < 0.05). Also, we determined that Se and/or ACA treatment together with DOXR application decreased the TNF-α, Cas-3, and TRPM2 channel expression levels in the cardiac tissue. The data showed that administration of Se and/or ACA treatment together with DOXR may be used as a therapeutic agent in preventing DOXR-induced cardiotoxicity.

• Authors: Kenan Yıldızhan, Zübeyir Huyut, Fikret Altındağ
• Journal: Biological trace element research (Biol Trace Elem Res) Vol. 201 Issue 5 Pg. 2458-2469 (May 2023) ISSN: 1559-0720 [Electronic] United States
• PMID: 35922740 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Selenium
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Poly(ADP-ribose) Polymerase Inhibitors
• TRPM Cation Channels
• Dimethyl Sulfoxide
• Glutathione
• Doxorubicin
• Calcium
• Trpm2 protein, rat

Topics

• Rats
• Female
• Animals
• Selenium (pharmacology, metabolism)
• Reactive Oxygen Species (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Poly(ADP-ribose) Polymerase Inhibitors (pharmacology)
• TRPM Cation Channels (metabolism)
• Dimethyl Sulfoxide (pharmacology)
• Cardiotoxicity (prevention & control)
• Oxidative Stress
• Glutathione (metabolism)
• Doxorubicin (toxicity)
• Apoptosis
• Calcium (metabolism)