Introduction
Reactive oxygen species (ROS) are a group of fundamental molecules in organisms. They can be neutral as 1O2, ionic as O2•− or radicals asOOH. However, under oxidative stress, these molecules are capable of causing damage to an organism through oxidation reactions in biological molecules of physiological importance, for example, proteins,1 lipids2,and DNA.3 Oxidative stress is the imbalance between the generation and consumption of ROS and is associated with widely distributed diseases, especially cancer,4 lung disorders,5 cardiovascular disorders, and atherosclerosis.6
Pro-oxidant molecules are any endobiotic or xenobiotic that produces oxidative stress, either by providing oxidative species such as ROS or by inhibiting the physiological mechanisms responsible for reducing the ROS concentration in the organism.7 Among pro-oxidant are found photosensitizers, which are molecules that can produce and increase the level of ROS and generate oxidative stress through two main mechanisms. These molecules can produce ROS through the type I mechanism, where an O2•− molecule is provided through the electron transfer mechanism from the photosensitizer to the oxygen molecule or through the type II mechanism, where 1O2 is obtained by transferring the excitation energy from the photosensitizer to oxygen molecule.8,9
Amphotericin B is a heptaene macrolide drug that is used as a broad-spectrum antibiotic. It has been considered for several decades as the standard for the treatment of systemic fungal and yeast infections. Several mechanisms have been proposed to explain the antifungal activity of amphotericin B. The most studied mechanism regarding antifungal activity is when amphotericin B interacts with ergosterol in the fungal cell membrane; in this way, a channel that connects the intracellular and extracellular medium through the cell membrane is formed and thereby promoting ions exchange that causes disruption of cellular homeostasis and consequently leads to cell death.10,11,12 The selectivity observed between the cell membranes of animals and fungi is based on higher intermolecular interactions between amphotericin B and ergosterol (in fungi) than the former with cholesterol (in animals).13,14 However, a second mechanism has been proposed that enables us to understand the antibiotic property of amphotericin B. In this mechanism, it was suggested that this molecule can act as a pro-oxidant molecule and produce oxidative stress through the generation of ROS.15 As observed in a study in which Aspergillus terreus was used (as it is resistant to amphotericin B), it was reported that the level of catalase production in A. terreus was significantly higher than in A. fumigatus (non-resistant to amphotericin B); this higher production level may contribute to amphotericin B resistance in A. terreus,since oxidative damage has been implicated in the action of amphotericin B;16 in addition, singlet oxygen (1O2) generation of amphotericin B under UVA was only below to nalidixic acid in a study on the production of singlet oxygen in a group of antiobiotics;17 in the same sense, the intracellular induction of ROS was determined in different pathogenic yeast species and it was found that amphotericin B induces the formation of ROS in all the species tested; hence, the data demonstrate that the production of ROS by amphotericin B is an essential mechanism of action that correlates with the fungicidal effect.18 The observed selectivity between fungi and animals in this second mechanism is based on a higher susceptibility to oxidative damage by ROS of ergosterol, compared to cholesterol in the cell membrane.19-21