Page 317 - The Toxicology of Fishes

Reactive Oxygen Species and Oxidative Stress 297

O
O

OH O
O
Juglone
1,6-Benzo(a)pyrene quinone

CH 3 NO 2
O N NO 2
2

NO 2

2,4,6-Trinitrotoluene (TNT) 1–Nitropyrene

O
C CH
C–N+ N+–CH 3 3
H 3
N
OH
Paraquat N–hydroxy–2–acetylaminofluorene

CH 3
N N N
CH 3
4–Dimethylaminoazobenzene

FIGURE 6.6 Representative redox-cycling chemicals including a natural product (juglone), a metabolite of the procar-
cinogen benzo(a)pyrene (1,6-benzo(a)pyrene quinone), the explosive 2,4,6-trinitrotoluene (TNT), a common combustion
byproduct (1-nitropyrene), an herbicide (paraquat), a carcinogenic aromatic hydroxylamine (N-hydroxy-2-acetylaminoflu-
orene), and an azo dye (4-dimethylaminobenzene).

cytotoxicity, immunotoxicity, and carcinogenicity (Bolton et al., 2000). Quinone toxicity can result from
ROS generation via redox cycling as well as from direct alkylations of protein and DNA.
Paraquat (Figure 6.6) and diquat are broad-spectrum, bipyridyl-based herbicides that have been used
extensively in no-till farming and marijuana control (paraquat) and for the control of nuisance aquatic
plants (diquat). The toxicity of these compounds to plants is based on their efficiency as redox cyclers
in chloroplasts that copiously transfer electrons and generate O during photosynthesis (Bowler et al.,
2
1994). Their toxicity to animals also involves their ability to redox cycle and produce oxidative stress.
Paraquat is unusual in that, regardless of route of exposure in mammals, it is selectively toxic to lung
tissue. This phenomenon appears to be due to its propensity to be actively transported by systems involved
in the transport of polyamines such as putrescine (Smith and Wyatt, 1981). Polyamines are endogenous
compounds that, like paraquat, contain positively charged quaternary nitrogen atoms. They are involved
in cellular growth and differentiation and are actively taken up by lung cells; thus, the selectivity of
paraquat to lung tissue appears to be due to its active transport by these cells, which have high O 2
concentrations that facilitate redox cycling.