Preface

Free radicals are highly unstable and react quickly with the nearest stable molecules, "stealing" their electrons to gain stability and, in this way, initiating a chain reaction and propagation until finally attaching the vital molecules of cell and cell membrane thus disrupting their integrity. Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions. Enzymatic reactions, which serve as the source of free radicals, include those involved in the respiratory chain, phagocytosis, prostaglandin synthesis, and the cytochrome P-450 system.

Oxidative stress, arising as a result of an imbalance between free radical production and antioxidant defenses, is associated with damage to a wide range of molecular species including lipids, proteins, and nucleic acids. Short-term oxidative stress may occur in tissues injured by trauma, infection, heat injury, hypertoxia, toxins, and excessive exercise. These injured tissues produce increased radical-generating enzymes (e.g., xanthine oxidase, lipogenase, cyclooxygenase), activation of phagocytes, release of free iron, copper ions, or a disruption of the electron transport chains of oxidative phosphorylation, producing excess reactive oxygen species (ROS).

This book highlights various issues of free radical biology from the perspective of antioxidant defense mechanisms. It is dived into two sections: "Redox Biology and Medicine" and "Antioxidants." The first chapter in Section 1 is "Introductory Chapter: Free Radical Biology in Metal Toxicities—Role of Antioxidants." This chapter explains how oxygen metabolism induces overproduction of free radicals due to altered pathophysiology in the system, and how inadequate antioxidants in the body induces impaired body defense systems and inability to fight against pollutants, particularly heavy metals. The chapter concludes that mode of action of free radical-generated oxidative stress typically starts with the reaction of heavy metals with target molecules and ends with toxic manifestations. These processes of oxidative stress and oxidant and antioxidant imbalances play a key role in free radical biology. Chapter 2, "Physiological Functions of Mitochondrial Reactive Oxygen Species," discusses the mechanisms regulating mitochondrial physiology and homeostasis. Production of mitochondrial reactive species (mROS) may have significant potential for the development of novel therapeutic strategies for the treatment of a wide range of human pathologies. Chapter 3, "Role of Oxidative Stress in the Cardiovascular Complications of Kawasaki Disease" elaboartes on a complex framework of events contributing to the etiology of Kawasaki disease (KD). This chapter provides new lines of evidence supporting the hypothesis that systemic oxidative stress together with premature aging of red blood cells and platelets could play a critical role in the cardiovascular risk observed in patients with KD. Chapter 4, "Radiation-Generated ROS Induce Apoptosis via Mitochondrial" describes the role of mitochondria and characterizes the proteins involved in Ionizing Radiation(IR)-induced apoptosis. Further, the chapter concludes that IR triggers the activation of anti-apoptotic proteins and enhances the risk of a second type of cancer in patients undergoing radiotherapy. In addition to increasing the radioresistance of cells, anti-apoptotic proteins can also stimulate uncontrolled cell proliferation that culminates in mutagenesis.

Section 2, "Antioxidants," includes two chapters. Chapter 5, "Effects of Oxidative Stress on Spermatozoa and Male Infertility," examines the delicate balance between ROS necessary for physiological activity and antioxidants to protect from cellular oxidative injury, both of which are essential for fertility. The chapter authors suggest that determination of the appropriate antioxidant compounds as well as their dosages, whether used in clinical practice or cryopreservation, need to be explored.

Finally, Chapter 6, "Nonenzymatic Exogenous and Endogenous Antioxidants" explains the chemical structure and mechanism of action of the most important non-enzymatic small exogenous and endogenous organic molecules that act as antioxidants. The chapter authors further conclude that the regulation of gene expression by employing oxidants and antioxidants represents a novel approach with promising therapeutic implications.

This book enriches the understanding of oxidative stress biology with reference to some specific antioxidant defense mechanisms. It is designed for students, researchers, and general readers with an interest in the subject matter.

We acknowledge the support of Dr. Shrilaxmi Bagali, Dr. Sayandeep K. Das, Dr. Aravind V. Patil, and Dr. Ishwar B. Bagoji for their help during the publication of this book.

> **Kusal K. Das, PhD, FRSB** Professor of Physiology, Laboratory of Vascular Physiology and Medicine, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, India
