Pathophysiological Aspects of Inflammation and Drug Design: an Updated Overview
Rachelle Etienne, Flávia Pereira Dias Viegas, Cláudio Viegas
Abstract
Inflammation is a natural response of the organism to damage, injury or tissue lesions caused by foreign matter, trauma, infection, immune reactions and tissue necrosis. As being a protection response, inflammation onset and progression involve immune cells, blood vessels and a number of molecular mediators. Once the inflammatory process begins, it is associated to the release of chemical substances, such as cytokines and chemokines (e.g. TNF-, lipoxynes, kinins, prostaglandins, leukotrienes) and cellular signaling proteins in the tissue environment and migration cells. As a result of a wealth knowledge through decades of research in fields like physiology, pharmacology and molecular biology, since 1980's a more comprehensive vision emerges, recognizing the inflammatory process as a complex result of an interconnected biochemical and cellular events, acting as a driving force associated to many chronic diseases, including obesity, diabetes, arteriosclerosis, cancer and neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's diseases (AD), responsible by severe social-economic impacts in population worldwide. During the last decades, the therapeutics and research of new drugs have been focused on the search and development of lower toxic non-steroidal anti-inflammatory agents, that could act mainly towards the arachidonic acid cascade, more specifically in the inhibition of COX-1, COX-2 and 5-LOX enzymes and modulating the production of prostaglandins, thromboxane and leukotrienes. More recently, the urge of more efficient, low toxic and more specific drugs to certain inflammatory conditions has directing the research for the development of novel drugs capable to act towards other inflammatory mediators, such as interleukins, TNF-, nitric oxide, kinase proteins, PPARs, endocannabinoid system, opioid receptors and proteins related to apoptosis, leading to the discovery of new drug candidates with different mechanisms of action, could also act in multiple inflammatory targets.