Cytotoxicity, Apoptosis, and Nitric Oxide

Abstract

Cell death plays an important physiological role during development and the turnover of cells in the tissue. However, the induction of excessive cell death by injury also contributes to various pathophysiological disorders. Toxic insults or ischemic injury can lead to the destruction of cells. Such cytotoxic effects are often the consequence of necrotic cell death. Necrotic processes are characterized by the disruption of cell homeostasis, energy depletion, organelle swelling, and random catalytic processes (1). The increase of plasma membrane permeability further leads to the release of the cell content into the extracellular milieu, which consequently evokes an inflammatory response. The induction of necrotic cell death during embryonal development or essential tissue cell turnover would have detrimental effects. Therefore, another kind of cell death was proposed to mediate these processes, which was initially termed “shrinkage necrosis” or “apoptosis” (Greek; apo:- apart; -ptosis:falling), referring to the cell death responsible for the falling of leaves in autumn (2). Given its strictly regulated nature, this kind of cell death was also termed “programmed cell death.” Apoptosis or programmed cell death refers to the morphological alterations exhibited by “actively” dying cells that include cell shrinkage, membrane blebbing, chromatin condensation, and DNA fragmentation (3). Finally, apoptotic cells expose specific molecules on the surface to initiate phagocytosis either by resident cells or by specialized phagocytes, thus ensuring that no intracellular material is released into the tissue and, therefore, preventing an inflammatory reaction (4). Thus, the apoptotic process is often referred to as “silent cell death.”