Evaluation of the Cardiac Protection Conferred by Proanthocyanidins in Grape Seeds against Development of Ehrlich Solid Tumors in Mice.

Maha Abdulrahman Aldubayan

doi:10.1155/2020/3530296

Abstract

Examination of the antineoplastic effects of a range of chemical compounds is often undertaken via the transplantable tumor model of Ehrlich solid tumor (EST), which is a simulation of breast cancer. The purpose of this study was to explore how cardiac toxicity, damage, oxidative stress, and changes in the expressions of TNFα and apoptotic P53 triggered by EST could be countered with grape seed proanthocyanidins (GSPE). To that end, 50 female mice were used, with arbitrary and equal distribution into five groups, namely, the control group (G1), GSPE group (G2), EST group (G3), GSPE + EST (G4; cotreatment consisted of mice that received GSPE treatment at the beginning of EST induction over a period of 14 days), and EST + GSPE (G5; posttreatment consisted of mice with EST that received GSPE treatment for 14 days following the 14 days since the induction of EST). By comparison with the control group, the EST group had significantly higher levels of serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatine kinase MB (CK-MB), myoglobin, cardiac TBARS, nitric oxide (NO), total thiol and hydrogen peroxide, cardiac damage, and expression of P53 and TNFα. On the other hand, the EST group had significantly lower levels of cardiac catalase and total antioxidant (TAC) than the control group. Furthermore, better improvement in cardiac toxicity, oxidative stress, damage, apoptosis, and TNFα expressions was displayed by the cotreated (GSPE + EST) group than by the posttreated (EST + GSPE) group. This led to the conclusion that GSPE conferred cardiac protective and antioxidant effects against EST. This finding calls for more investigation on the benefits of grape seeds as adjuvant agents to prevent and treat cardiac toxicity.

Highlights

Conditions underpinned by multiple factors lead to cardiac dysfunction [1, 2]
Resembling human breast cancer, Ehrlich carcinoma represents an undifferentiated carcinoma that starts out as hyperdiploid, has a high capacity for transplantation, does not regress, proliferates quickly, has a brief life-span, is fully malignant, and lacks a tumour-specific transplantation antigen [29]. e purpose of this study was to investigate the extent to which grape seed proanthocyanidins extract (GSPE) had a protective effect against cardiac toxicity, oxidative stress, damage, apoptosis, and tumor necrosis factor-α (TNFα) alterations caused by Ehrlich solid tumor (EST) in mice. is is the first publication describing a method to test how breast cancer affects cardiac structure and function using a novel mice model. e results obtained suggested that cardiac function, as well as the function of other important organs, was affected by tumor formation
By comparison with the control group, the EST group exhibited significantly higher levels of lactate dehydrogenase (LDH), CK, CK-Mb, and myoglobin in the serum (P < 0.01), providing evidence that cardiac dysfunction in mice was caused by EST

Summary

Introduction

Conditions underpinned by multiple factors (e.g., chronic heart failure, kidney failure, metabolic disorders, and cancer) lead to cardiac dysfunction [1, 2]. No other disease affecting humans is more severe and is associated with a greater mortality rate than cancer [3]. E onset of cancer is triggered owing to cell DNA mutations causing the formation of an extraneous tissue mass known as a tumor. Indirect activation of apoptosis is caused by numerous cancer treatments through chemical or physical damage to DNA [4]. Just like congestive heart conditions, cardiomyopathy triggered by cancer leads to cardiac dysfunction, which is associated with cardiac atrophy, metabolic remodelling, fibrosis, and cardiac ultrastructure alterations [5]. Examination of the antineoplastic effects of a range of chemical compounds is often undertaken via the transplantable tumor model of Ehrlich solid tumor (EST), which is a simulation of breast cancer [6,7,8]

Methods

Results

Conclusion