Ameliorative Effect of Almond Oil Against Doxorubicin-Induced Cardiotoxicity in Mice Via Downregulation of TLR4 Gene Expression, Lowering NF-κB and TNF-α Levels

Abstract

D oxorubicin is an anthracycline antibiotic. It is also known as adriamycin. Doxorubicin is commonly used in the chemotherapy of breast cancer, lung cancer, leukemia and solid tumors (Xinyong et al., 2020). This cardiotoxicity has serious implications, resulting in a bad prognosis and deaths for up to 61% of patients (Wouters et al., 2005).Previous studies stated that the doxorubicin induced cardiac toxicity involves generation of huge amounts of reactive oxygen and reactive nitrogen species (ROS and RNS) which can obviously cause cardiac toxicity (Gilliam and research Article Abstract | Doxorubicin is a chemotherapeutic drug broadly used for the treatment of a wide range of malignancies.Many studies have shown that natural compounds derived from plants have medicinal and antioxidant properties. The purpose of the current investigation was to investigate if almond oil could protect male mice against doxorubicininduced cardiotoxicity. The experimental mice were divided into three groups; control group: received 0.9 percent saline, doxorubicin group: Mice were intraperitoneal injected with doxorubicin (5 mg/kg) ithree times over a period of two weeks (dose every five days) and almond oil group: Mice were administered almond oil orally (2.26 g/kg) using oral gavage daily over a period of three weeks, one week prior to the doxorubicin injection and two weeks along with doxorubicin injection. The effects and mechanisms of doxorubicin on superoxide dismutase activities were elucidated by molecular docking studies. Treatment with almond oil attenuated lipid peroxidation, improved superoxide dismutase (SOD) activities that are associated with doxorubicin administration. Also almond oil considerably modulated the gene expression of toll like receptor 4 (TLR4) and lowers the serum levels of both nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α). The elevated levels of Creatine Kinase -MB (CK-MB), Lactate Dehydrogenase (LDH), and Troponin-1 induced by doxorubicin injection were neutralized by almond oil supplementation. Almond oil ameliorated all the histological alterations caused by doxorubicin. The administration of almond oil with doxorubicin modulated the doxorubicin-induced changes in serum and cardiac tissue in mice due to its anti-inflammatory and antioxidant properties.