Page 294 - The Toxicology of Fishes

274 The Toxicology of Fishes

Studies with Fishes ................................................................................................................................301
Basic Biochemical and Molecular Mechanisms of Oxidative Stress in Fish............................. 301
In Vitro Biochemical Generation of ROS ..........................................................................301
Enzymatic Antioxidant Defenses in Fish...........................................................................301
Nonenzymatic Antioxidant Defenses in Fish.....................................................................303
In Vivo Prooxidant Studies in Fish.....................................................................................303
Differences between Fish and Mammals...........................................................................303
Biomarkers of Oxidative Stress ...................................................................................................305
Oxidative Stress and the Health of Wild Fish Populations.........................................................307
Future Directions ...................................................................................................................................307
References..............................................................................................................................................308

Introduction
Mechanisms underlying the toxicity of numerous environmental pollutants are discussed throughout this
book. The purpose of this chapter is to describe a particular set of phenomena that collectively comprise
an important mechanism of chemical toxicity and cellular defense. These phenomena, referred to as
oxidative stress, apply to a diverse array of chemicals and result in a diverse array of ultimate health
outcomes. The study of oxidative stress broadly includes biological phenomena associated with the
generation of reactive oxygen species (ROS), molecular systems designed to protect cells from ROS
(often referred to as antioxidant defense systems), and the deleterious impacts of ROS. An excellent
detailed monograph on this subject is Halliwell and Gutteridge (1999).
As in many areas of mechanistic toxicology, understanding of oxidative stress in fishes has lagged
behind understanding in mammals and, indeed, has depended to a large degree on studies in other
biological systems for the development of methodologies and concepts; however, the study of oxidative
stress in fishes is currently an active area of investigation that is revealing a number of important
similarities and differences with other organisms. Moreover, the multitude of chemicals entering fresh-
water and marine systems that can contribute to oxidative stress underlies the need for information on
this phenomenon in fishes. In this chapter, we describe fundamental aspects of ROS chemistry and
generation, antioxidant defense systems, cellular and organismal impacts, and specific mechanisms by
which pollutants play roles in these processes. We also describe the current state of understanding of
oxidative stress in fishes, including comparisons with other organisms.

Reactive Oxygen Species and Free Radicals
Oxygen (as dioxygen, O ) currently accounts for about 21% of the Earth’s atmosphere, and oxygen is
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the most abundant element in the planet’s crust (at 54%); however, life first evolved under essentially
anaerobic conditions, and O is believed to have first appeared as a byproduct of photosynthesis by blue-
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green algae (cyanobacteria) beginning about 2.5 billion years ago (Harman, 1986). As atmospheric O 2
gradually rose over the ensuing millennia, several notable developments occurred:

1. Organisms remaining anaerobic either retreated to anaerobic microenvironments or perished
due to the effects of O such as oxidation of metabolic intermediates (such as thiols, iron, and
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pteridines), enzyme inhibition (such as occurs with nitrogenases), and effects of ROS generated
during oxidations.
2. Aerobic organisms evolved that took advantage of the electron-accepting capacity of O . The
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energetic efficiency of O as an electron acceptor over those employed by anaerobes (iron and
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sulfur, for example) enhanced the evolution of more advanced life forms (i.e., eukaryotic
organisms). This switch required the concomitant development of mechanisms to protect these
organisms from the toxic effects of O .
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3. Ozone (O ) levels in the atmosphere rose, giving organisms protection from intense solar
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ultraviolet radiation; this also enhanced eukaryotic evolution.