Abstract

Adriamycin (ADR) or Doxorubicin (DOX), is an effective antineoplastic agent commonly used for the treatment of various cancers. ADR is an anthracycline chemotherapeutic containing a quinone group that is known to produce reactive oxygen species (ROS) in heart. . Because of its cardiotoxicity side effects in various tissues, which lead to cardiomyopathy and congestive heart failure, the clinical application is limited. The present study was designed to evaluate the cardioprotective effect of nano-magnetic particles (NFe3O4) and Graviola (Annona muricata) leaves extract and combination of them against ADR -induced cardiomyopathy in rats which are divided into 5 groups including one control and four experimental (10 rats per group). They received saline (normal), ADR alone (15 mg/kg body weight, i.p.) (control), ADR followed by NFe3O4 (15 mg/kg body weight, i.p.), ADR followed by Graviola (200mg/kg body weight, oral), and ADR followed by NFe3O4 and Graviola. Animals were sacrificed 28 days after treatment and evaluations were made by measuring cardic enzymes (CK and LDH) in serum. Also the activities of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) as well as the level of malnodialdhyde (MDA) as a marked of lipid peroxidation . In the ADR-exposed rats,CK, LDH, and MDA significantly increased, while GSH, SOD and CAT enzymes decreased when compared to normal animals. In the Group NFe3O4, graviola leaves extract, and (NFe3O4 +graviola leaves extract alone), CK, LDH and MDA levels significantly decreased, while GSH, SOD and CAT enzymes levels significantly increased when compared to ADR treated animals. The results showed that there is a possibility that the ethanolic extract of graviola and NFe3O4 and combination of them ameliorate the toxicity induced by ADR in rats.

Highlights

  • Adriamycin (ADR) is an effective antineoplastic drug commonly used to treat different types of cancer such as ovarian, thyroid, gastric, breast, non-Hodgkin's and Hodgkin's lymphoma, multiple myeloma, and sarcomas (Cortés-Funes and Coronado, 2007)

  • In ADR treated animals a highly significant increase in the level of cardiac markers i.e creatine kinase (CK) and lactate dehydrogenase (LDH) at (p

  • The CK level in NFe3O4, graviola and (NFe3O4 + graviola leaves extract alone) treated animals showed a highly significant decrease at (p

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Summary

Introduction

Adriamycin (ADR) is an effective antineoplastic drug commonly used to treat different types of cancer such as ovarian, thyroid, gastric, breast, non-Hodgkin's and Hodgkin's lymphoma, multiple myeloma, and sarcomas (Cortés-Funes and Coronado, 2007). Studies around its cardiotoxicity which cause cardiomyopathy and congestive heart failure side effect (Swain et al, 2003 and Carvalho et al, 2009 ). This side effect is mainly due to ADR–mediated free radical formation (DeAtley et al, 1998). Topoisomerase II can be activated by ADR that caused breaks in DNA strands and forming quinine type of free radicals. Olson (1990) declared that Tissues with less developed antioxidant defense mechanism such as the heart are highly susceptible to injury by anthracycline induced oxygen radicals. Many investigators have described the role of reactive oxygen species including hydroxyl radical in ADR–induced cardiotoxicity (Sarvazyan et al, 1995)

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