PARAQUAT

• living in rural areas (Ho et al 1989; Golbe
et al 1990; Butterfield et al 1993; Liou et al
1997); and/or
• drinking well water (Smargiassi et al 1998;
Gatto et al 2009; Willis et al 2010).
Medical cases add to the evidence. Two
individual cases were reported by Bocchetta &
Cosini (1986) “in relation with the direct use of
pesticides”. Both were early onset cases, one a
41-year-old farmer using pesticides extensively,
and the other a 38-year-old worker at a chemical
plant making petroleum derivatives and
pesticides.
So there is substantial evidence linking
Parkinson’s disease with exposure to pesticides.
The question now is whether paraquat is one of
the causative pesticides.
There are three individual pesticides particularly
linked to Parkinson’s disease: rotenone, maneb,
and paraquat (Hatcher et al 2008).
Paraquat and Parkinson’s: laboratory
studies
Numerous laboratory studies demonstrate
the plausibility of paraquat as able to cause
the onset, or accelerate the development, of
Parkinson’s disease (Hatcher et al 2008).
Animal studies have shown that paraquat
causes degenerative brain changes that are
the pathological hallmarks of Parkinson‘s
disease. Parkinson’s is characterised by a
progressive loss of dopamine neurons in
the substantia nigra region of the brain, the
presence of ubiquitin- and a-synuclein-positive
cytoplasmic inclusions known as Lewy bodies,
depigmentation of the locus ceruleus, and
autonomic dysfunction (Hatcher et al 2008).
Dopamine is a neurotransmitter involved in the
control of muscular movement.
Paraquat has been shown to cause dosedependent
loss of dopamine neurons and
degeneration of the nigrostriatal dopamine
system; aggregation of a-synuclein and
formation of Lewy bodies; and decreased or
altered locomotor activity (e.g. Liou et al 1996;
Brooks et al 1999; Uversky et al 2001; Manning-
Bog et al 2002; McCormack et al 2002; Mollace
et al 2003; Chanyachukul et al 2004; Peng et al
2004; Li et al 2005; Ossowska et al 2005; Dinis-
Oliveira et al 2006; Purisai et al 2007; Yang &
Tiffany-Castiglioni 2007; Somayajulu-Nițu et al
2009; Choi et al 2010; Songin et al 2010).
Although the mechanism by which paraquat
causes these effects in the brain is not fully
understood, there are indications that it may be
via oxidative stress and the formation of free
radicals (Mollace et al 2003; Yang 2005; Castello
et al 2007; Li et al 2007; Kang et al 2009; Chen
et al 2010a). Paraquat is known to cause
production of ‘reactive oxygen species’, such
as suproxide, which cause oxidative damage in
brain mitochondria (Dreschel & Patel 2009).
Paraquat has the ability to cross the blood-brain
barrier (Shimizu et al 2001; Dinis-Oliveira et al
2006) and enter the brain (Lee 2008a). It persists
in mouse midbrain tissue with a half-life of 28
days, and this persistence may contribute to
prolonging adverse effects (Prasad et al 2007).
The uptake of paraquat into the brain is agedependent,
with higher concentrations found
in very young and very old in animal studies
(Thiruchelvam et al 2002).
The effect of paraquat in inducing Parkinson‘s
disease or symptoms is heightened by
synergistic interaction with the fungicide maneb,
and the adverse effects of the combination occur
at low doses in animal studies (Thiruchelvam et
al 2000a, 2000b; Thrash et al 2007). Males have
shown greater vulnerability to this combination,
and aging increases vulnerability (Dinis-Oliveira
et al 2006; Thiruchelvam et al 2003). Vulnerability
is also increased in people with certain genetic
variations relating to dopamine transport: males
with 2 or more of the susceptible alleles of the
gene, and who were occupationally exposed
to maneb and paraquat, had an almost 3-fold
risk of Parkinson’s compared to those without
the genetic variation (Ritz et al 2009). In other
words there is an interaction been genetics and
the pesticides.
Another dithiocarbamate fungicide closely
related to maneb – nabam – has a similar
synergistic effect on paraquat, increasing tissue
concentration and altering dopamine transport
(Barlow et al 2003).
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