Effect of a nootropic drug on liver proteome from rats under induced chronic psychological stress

Abstract

Stress has become a public health problem in emerging countries, as a result of the actual lifestyle. In Mexico, according to the World Health Organization, work stress is already at the top of the world ranking. Stress is an adaptive response of an organism to a stressful situation. At a physiological level, stress can lead to an imbalance between the release of free radicals and antioxidant defenses, causing cell damage on membrane lipids, proteins, and DNA. This response has been associated with neurodegenerative diseases, atherosclerosis, Mellitus diabetes, cancer, or immune system alterations. One of the therapies utilized to combat the physiological effects produced by the psychological stress in the brain is the use of nootropic drugs, due to its function on modulating neurotransmission, on restoring membrane fluidity, on inhibiting lipid peroxidation, and on slowing oxygen consumption in mitochondria. To evaluate the effect of nootropic piracetam on other organs like liver, rats were exposed to chronic psychological stress due to predator odor, and an analysis of liver proteome was carried out by 1-DE-nanoLC-MS/MS. Functional analysis of identified proteins showed differences between the stressed rats treated or not treated with the nootropic drug. In stressed rats, liver proteome manifested a significant down- or upregulation in proteins from 10 and 19 pathways, respectively. When the nootropic drug was supplied to stressed rats, 14 pathways were downregulated, and 12 were upregulated, restoring the non-stressed rat liver proteome. Moreover, stressed rats treated with the nootropic drug showed a greater number of antioxidant enzymes identified in liver than non-stressed ones. Therefore, this drug could return the normal molecular level and stimulate the synthesis of antioxidant enzymes under stress conditions, reflected in the liver proteome.