321
Chapter fourteen: Toxicology and poisons
which also produces biliverdin. While biliverdin is water soluble and rapidly excreted, biliverdin reductase (BVRA) reduces biliverdin to bilirubin which is not water soluble and a
well-known neurotoxicant (Ostrow et al. 2004). Barañano et al. (2002), among others, noted
the ostensive paradox of an energy-requiring process evolving which converts a non-toxic
product into a toxic compound. However, CO, as well as other products of the breakdown
of heme protein (such as bilirubin and biliverdin) are known to have antioxidant properties as well as protect against ischemia–reperfusion injury (Stocker et al. 1987; Barañano
et al. 2002). Barañano et al. (2002) found that relatively low concentrations of bilirubin
have cytoprotective effects through redox cycling with bilverdin reductase (BVRA), and
that BVRA might be more important than traditional antioxidants such as glutathione in
oxidative cytoprotection. There is some evidence to suggest that marine mammals have
higher rates of endogenous production of antioxidants (including glutathione, superoxide
dismutase, and glutathione peroxidase) compared to terrestrial mammals, presumably as
an adaptation or acclimation to dealing with periods of apnea (Wilhelm Filho et al. 2002).
This will alter their response to environmental poisons unrelated to molecular oxygen
products and by-products of cellular respiration.
14.5 Metals and detoxification
High trophic level feeding marine mammals (fish and marine mammal eating) often have
high concentrations of some elements (Hg, Se) compared to many terrestrial mammals,
while cadmium (Cd) is often associated with consumption of invertebrates (Dehn et al.
2005). Despite reports of concentrations above levels of concern in other mammalian species (Dietz et al. 1998, 2013; Rea et al. 2013) there have been few reports of poisoning events
(signs of toxicosis) associated with heavy metals, although this may be due to the difficulties associated with performing detailed clinical assessments and necropsies on marine
mammals of suitable condition.
There has been speculation that Arctic marine mammals have adapted to high levels
of cadmium (Dietz et al. 1998). Temporal trends assessments for Cd in the Arctic environment in the last few decades do not yield themselves to clear interpretation (Riget and
Dietz 2000), and it is conceivable that Cd has been at appreciable levels at least since the
fifteenth century (Hansen et al. 1989). The toxic effects of Cd have been known for several
decades, the most infamous poisoning event occurring in Japan’s Toyama Prefecture in
the early 1900s, although the link between the “itai-itai” (ouch-ouch) disease and Cd was
not reported until 1968. Cadmium accumulates in the kidney and the liver and is a wellknown nephrotoxin, where it causes glomerular and tubular damage (for review of toxicity in humans see Godt et al. 2006). Chronic Cd poisoning is associated with a number
of bone maladies, including osteoporosis and increased occurrence of fractures, both of
which appear to be due to decreased rates of bone mineralization. This is likely related to
renal dysfunction (Berglund et al. 2000), although the exact mechanisms for altered mineralization due to Cd toxicity in unknown.
Metallothioneins (MTs) are a conserved family of proteins among mammals, with isoforms identified in a number of species of marine mammals (for review see Das et al. 2000). The
element-binding metallothioneins function in uptake, transfer, and excretion of both essential
(such as Cu and Zn) and nonessential metals (such as Ag, Hg, Cd). The majority of metal interactions (binding sites) take place on thiol groups of cysteine residues, which can account for
up to 30% of MT residues. Metallothioneins have been postulated to be involved in defending
organisms against heavy metals such as Hg and Cd, where metals bound to MT are less toxic
than free metals. The relationship between MTs and Hg is not clear—binding of Hg to MTs in
Chapter fourteen: Toxicology and poisons
which also produces biliverdin. While biliverdin is water soluble and rapidly excreted, biliverdin reductase (BVRA) reduces biliverdin to bilirubin which is not water soluble and a
well-known neurotoxicant (Ostrow et al. 2004). Barañano et al. (2002), among others, noted
the ostensive paradox of an energy-requiring process evolving which converts a non-toxic
product into a toxic compound. However, CO, as well as other products of the breakdown
of heme protein (such as bilirubin and biliverdin) are known to have antioxidant properties as well as protect against ischemia–reperfusion injury (Stocker et al. 1987; Barañano
et al. 2002). Barañano et al. (2002) found that relatively low concentrations of bilirubin
have cytoprotective effects through redox cycling with bilverdin reductase (BVRA), and
that BVRA might be more important than traditional antioxidants such as glutathione in
oxidative cytoprotection. There is some evidence to suggest that marine mammals have
higher rates of endogenous production of antioxidants (including glutathione, superoxide
dismutase, and glutathione peroxidase) compared to terrestrial mammals, presumably as
an adaptation or acclimation to dealing with periods of apnea (Wilhelm Filho et al. 2002).
This will alter their response to environmental poisons unrelated to molecular oxygen
products and by-products of cellular respiration.
14.5 Metals and detoxification
High trophic level feeding marine mammals (fish and marine mammal eating) often have
high concentrations of some elements (Hg, Se) compared to many terrestrial mammals,
while cadmium (Cd) is often associated with consumption of invertebrates (Dehn et al.
2005). Despite reports of concentrations above levels of concern in other mammalian species (Dietz et al. 1998, 2013; Rea et al. 2013) there have been few reports of poisoning events
(signs of toxicosis) associated with heavy metals, although this may be due to the difficulties associated with performing detailed clinical assessments and necropsies on marine
mammals of suitable condition.
There has been speculation that Arctic marine mammals have adapted to high levels
of cadmium (Dietz et al. 1998). Temporal trends assessments for Cd in the Arctic environment in the last few decades do not yield themselves to clear interpretation (Riget and
Dietz 2000), and it is conceivable that Cd has been at appreciable levels at least since the
fifteenth century (Hansen et al. 1989). The toxic effects of Cd have been known for several
decades, the most infamous poisoning event occurring in Japan’s Toyama Prefecture in
the early 1900s, although the link between the “itai-itai” (ouch-ouch) disease and Cd was
not reported until 1968. Cadmium accumulates in the kidney and the liver and is a wellknown nephrotoxin, where it causes glomerular and tubular damage (for review of toxicity in humans see Godt et al. 2006). Chronic Cd poisoning is associated with a number
of bone maladies, including osteoporosis and increased occurrence of fractures, both of
which appear to be due to decreased rates of bone mineralization. This is likely related to
renal dysfunction (Berglund et al. 2000), although the exact mechanisms for altered mineralization due to Cd toxicity in unknown.
Metallothioneins (MTs) are a conserved family of proteins among mammals, with isoforms identified in a number of species of marine mammals (for review see Das et al. 2000). The
element-binding metallothioneins function in uptake, transfer, and excretion of both essential
(such as Cu and Zn) and nonessential metals (such as Ag, Hg, Cd). The majority of metal interactions (binding sites) take place on thiol groups of cysteine residues, which can account for
up to 30% of MT residues. Metallothioneins have been postulated to be involved in defending
organisms against heavy metals such as Hg and Cd, where metals bound to MT are less toxic
than free metals. The relationship between MTs and Hg is not clear—binding of Hg to MTs in