PARAQUAT

Mode of action in animals
Oxidative stress occurs when the production of
‘reactive oxygen species’, such as free radicals
and hydrogen peroxide, exceeds the body’s ability
to neutralise and eliminate them, overwhelming
antioxidant defences such as glutathione, and
resulting in DNA damage, and cell and tissue death.
Oxidative stress is involved in many human diseases,
including Parkinson’s disease, cancer, Alzheimer’s
disease, diabetes, and heart failure. Commonly
used measures of the extent of oxidative stress in
laboratory studies are the levels of glutathione and
associated enzymes of the antioxidant system such
as glutathione reductase, glucose-6-phosphate
dehydrogenase, glutathione-S-transferase, glutathione
peroxidase, catalase, and superoxide
dismutase. Alterations in the components of the
antioxidant system can be used as biomarkers for
paraquat poisoning (Ray et al 2007).
Paraquat causes extensive damage to the
mitochondria of cells through the production of
free radicals and oxidative stress, resulting in the
interruption of important biochemical processes,
cell death, and multi-organ failure (Suntres
2002; Mohammadi-Bardbori & Ghazi-Khansari
2008; Cocheme & Murphy 2009). Effects have
been measured in rats in the mitochondria of
brain cells (e.g. Castello et al 2007; Dreschel &
Patel 2009), in brain neurons (Yang & Tiffany-
Castiglioni 2005; Zaidi et al 2009), in blood, liver,
lung and kidney cells (Ray et al 2007); and in the
hippocampus of mice brain (Chen et al 2010a).
Systemic effects
Paraquat alters the levels and activity of various
enzymes in liver and kidney (Dere & Polat 2000);
and in serum, including acetycholinesterase (El-
Demerdash et al 2001).
US EPA (1997) reported decreased red blood
cells, haemoglobin, white blood cells, and serum
protein; increased polymorphonucleocytes
(types of white blood cells); altered ratios of liver
enzymes; increased potassium and glucose; and
decreased weight of a number of organs (heart,
liver, brain, kidneys, urinary bladder, ovaries,
thyroid, and adrenals) varying between male and
female rodents. IPCS (1984) reported increased
plasma concentrations of corticosteroids.
Diabetes
Paraquat is implicated in the development
of diabetes. Oxidative stress, a key effect of
paraquat, is thought to play an important role
in type II diabetes, through the development
of insulin resistance (Kimura et al 2007, 2010;
Shibata et al 2010). Paraquat has been shown to
inhibit insulin action in laboratory tests on rat liver
cells (it impaired the suppressive effect of insulin
on insulin-like growth factor-binding protein-1
gene expression) (Kimura et al 2007, 2010).
Another study showed that paraquat inhibits
insulin-dependent glucose uptake through
oxidative stress (Shibata et al 2010). Paraquat
has also been shown to cause hyperglycaemia
in sheep (Webb 1982-83).
Eyes
US EPA (1997) reported clouding of the lens,
and cataracts in rodents.
Lungs
US EPA (1997) reported chronic inflammation of
lungs, increased lung weight, deeper breathing,
thickened alveolar walls, fi brosis, oedema, and
alveolar haemorrhage in rodents.
It is clear that paraquat causes the development
of lesions in the lungs, although these appear
generally to be non-cancerous. According to
the Japanese pesticide industry (ICI Ltd Japan
& Otuska Chemical Ltd 1988), paraquat “can
induce a chronic proliferative and hyperplastic
lung lesion”, although “it was not tumorigenic
in this study” (referring to a study carried out
by Nippon Experimental Medical Research
Institute). The same study also reported a higher
incidence of lung adenomas in female rats but
denied their signifi cance (they were “within
historical range”).
Rats exposed to sublethal doses of paraquat
experienced decreases in aerobic performance
and mechanical efficiency, as well as increased
oxygen consumption during exercise (Lacerda
et al 2009).
Liver
US EPA (1997) reported cell proliferation and
fi brosis of the bile duct in rodents.
Kidneys
US EPA (1997) reported rough surface and
nephritis, and renal tubular degeneration in
rodents.
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