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

Jovana Bradic; Marijana Andjic; Jovana Novakovic; Aleksandar Kocovic; Marina Tomovic; Anica Petrovic; Marina Nikolic; Slobodanka Mitrovic; Vladimir Jakovljevic; Danijela Pecarski

doi:10.3390/antiox12061277

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

Antioxidants (Basel). 2023 Jun 15;12(6):1277. doi: 10.3390/antiox12061277.

Authors

Jovana Bradic^{1

2}, Marijana Andjic^{1

2}, Jovana Novakovic^{1

2}, Aleksandar Kocovic^{1

2}, Marina Tomovic¹, Anica Petrovic^{1

2}, Marina Nikolic^{2

3}, Slobodanka Mitrovic⁴, Vladimir Jakovljevic^{2

3

5}, Danijela Pecarski⁶

Affiliations

¹ Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
² Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Svetozara Makovica 69, 34000 Kragujevac, Serbia.
³ Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁴ Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia.
⁵ Department of Human Pathology, 1st Moscow State Medical, University IM Sechenov, Moscow 119991, Russia.
⁶ The College of Health Science, Academy of Applied Studies Belgrade, 11000 Belgrade, Serbia.

Abstract

This study aimed to examine the effects of a 14-day treatment with lady's bedstraw methanol extract on doxorubicin-induced cardiotoxicity through functional, biochemical and histological examinations. We used 24 male Wistar albino rats divided into the following groups: control (CTRL), doxorubicin (DOX), and DOX + GVE (Galium verum extract). GVE was administered orally at a dose of 50 mg/kg per day for 14 days, while a single dose of doxorubicin was injected into the DOX groups. After accomplishing treatment with GVE, cardiac function was assessed, which determined the redox state. During the autoregulation protocol on the Langendorff apparatus, ex vivo cardiodynamic parameters were measured. Our results demonstrated that the consumption of GVE effectively suppressed the disturbed response of the heart to changes in perfusion pressures caused by administration of DOX. Intake of GVE was associated with a reduction in most of the measured prooxidants in comparison to the DOX group. Moreover, this extract was capable of increasing the activity of the antioxidant defense system. Morphometric analyses showed that rat hearts treated with DOX showed more pronounced degenerative changes and necrosis compared to the CTRL group. However, GVE pretreatment seems to be able to prevent the pathological injuries caused by DOX injection via decrease in oxidative stress and apoptosis.

Keywords: cardiac function; doxorubicin-induced cardiotoxicity; lady’s bedstraw; oxidative stress; rat.

Grants and funding

The research was supported by the Ministry of Science, Technological Development and Innovation, Republic of Serbia through Grant Agreements with University of Kragujevac—Faculty of Medical Sciences No. 451-03-47/2023-01/200111.