“Pharmacological studies on the potential Neuroprotective effect of Caffeic Acid Phenethyl Ester against Doxorubicin-Induced Cognitive Impairment in Experimental Rat Model”

Abstract

Chemotherapy is the most commonly implemented strategy in cancer treatment, often used in conjunction with radiotherapy, surgery and/or hormonal treatment. Although chemotherapy is beneficial against several malignancies, it also affects healthy cells causing several adverse effects among which CNS toxicity, including cognitive impairment, is of particular concern. This cognitive impairment, often referred to as chemobrain, is characterized by the impairment of patients’ memory, learning, attention, concentration, reasoning, processing speed, executive functions, and visuo-spatial skills. This may occur with various types of solid tumors treatment, mainly breast, lung, prostate, and ovarian cancers among others. Cognitive impairment varies widely among patients, being transient with mild reversible manifestations (occurring during and after discontinuation of chemotherapy) in most cases. Doxorubicin (DOX) is a prominent mainstay member of the anthracycline antineoplastic agents; it is one of the most potent FDA-approved agents for the treatment of diverse types of tumors. Preclinical studies verified deficits in hippocampal-related learning and memory in animals treated with DOX. Administration of DOX was reported to induce biochemical alterations that encompass increased levels of peripheral inflammatory cytokines and brain oxidative damage. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic compound, is reputable for its potent antioxidant, anti-inflammatory, antitumor and neuroprotective properties. Since CAPE was shown to counteract neuronal inflammation, oxidative stress, mitochondrial impairment and neuronal cell death in different preclinical models, it is anticipated that it can afford protection against DOX-induced oxidative impairment through an interplay of various pathways.