Page 320 - The Toxicology of Fishes

300 The Toxicology of Fishes

Photosensitization
Ultraviolet (UV) radiation is typically divided into three general categories: UVC (200 to 280 nm),
UVB (280 to 320 nm), and UVA (320 to 400 nm). UVC is not environmentally relevant, as it is
effectively blocked by the Earth’s atmosphere; however, UVB and UVA radiation to differing degrees
do have the ability to penetrate the Earth’s atmosphere and water columns to depths dependent on
the wavelength of the radiation and the clarity of the water. Both are capable of generating ROS and
free radicals either directly or via excitation of photosensitizing chemicals, including both endoge-
nously produced compounds (Young, 1997) and many common pollutants of aquatic systems (Larson
and Weber, 1994). Many polycyclic aromatic hydrocarbons (PAHs), for example, are orders of
magnitude more acutely toxic to aquatic organisms, including fish, in the presence of ultraviolet
radiation than in its absence (Ankley et al., 1997; Arfsten et al., 1996; Bowling et al., 1983; El-
Alawi et al., 2002). Energy absorbed by the chemical bonds present in these compounds excites
electrons to higher energy orbitals; this energy can lead to changes in the chemical structure of the
PAH and in some cases reaction with other molecules, such as oxygen, in a process referred to as
photomodification (Huang et al., 1997; McConkey et al., 1997). The extra energy can also cause the
loss of an electron from the PAH, or the extra energy can be given off by the compound in a variety
of ways (Larson and Weber, 1994; Schwarzenbach et al., 1993). As an example, photosensitization
occurs when the energy gained by the PAH that absorbed the photon (the photosensitizer) is then
passed on to another molecule that would not have been chemically able to absorb that energy directly
from the photon, such as O (El-Alawi et al., 2002; Schwarzenbach et al., 1993). Both photosensi-
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tization and photomodification of PAHs can lead to the production of ROS; for example, when an
electron is lost, it is often absorbed by oxygen, leading to the production both of superoxide anion
and a radical compound. Similarly, when energy is lost from the excited compound, it can be
transferred to oxygen, producing the reactive singlet oxygen, which is highly reactive and toxic
(Briviba et al., 1997). Of course, high-energy radiation such as UV radiation can cause damage in
the absence of photosensitizers; however, although UV radiation has been shown to cause oxidative
stress, DNA damage, and other biological effects in fish (Charron et al., 2000; Fabacher et al., 1994;
Lesser et al., 2001), the environmental relevance of this source of oxidative stress to fish is unclear
(Williamson, 1995).

Diminished Antioxidant Defense

Although less studied than enhanced ROS production, interference with antioxidant defense system
components represents another mechanism by which chemicals can exert oxidative stress in animals.
Inhibition of antioxidant enzymes comprises an important component of this phenomenon; for
example, quinones have been shown to inhibit SOD activities (Smith and Evans, 1984). This effect
may be mediated by H O generated via redox cycling, as prolonged H O exposure can inhibit
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CuZnSOD and FeSOD (Halliwell and Gutteridge, 1999). Relatedly, extracts of diesel exhaust
particles were observed to effectively inhibit CuZnSOD in vitro, and this effect was surmised to be
associated with quinone components of the extracts (Kumagai et al., 1995). Dowla et al. (1996)
examined the effects of several chemicals used in agriculture (acephate, cadmium, methamidophos,
maleic hydrazide, and nicotine) on activities of human blood SOD, cholinesterase, and δ-aminole-
vulinic acid dehydrase (ALAD) and found SOD to be the most sensitive to inhibition by all chemicals
tested. Plant polyphenols such as chalcones and tannic acids were shown to be potent GR inhibitors
in vitro, with IC values in the micromolar range (Zhang et al., 1997). The relevance of such in
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vitro studies to in vivo exposures remains speculative. Methylmercury, however, was shown to inhibit
hepatic GPX activities and reduce GSH levels in rat pups; these effects were associated with
increased lipid peroxidation and hepatotoxicity. These results support the purported prooxidant role
of methylmercury, a metal complex that cannot directly generate ROS via redox cycling or Fenton
chemistry, as is the case for metals such as Fe and Cu. Moreover, the reactive nature of the sulfhydryl
group of GSH makes this critical antioxidant prone to depletion by a number of oxidants and
electrophiles.