Introduction
Reactive oxygen species (ROS) are a group of fundamental molecules in
organisms. They can be neutral as 1O2,
ionic as O2•− or radicals as•OOH. 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