ACUTE EXPOSURE OF Drosophila melanogaster TO PARAQUAT CAUSES OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION

Abstract

Paraquat (PQ; 1, 1'-dimethyl-4-4'-bipyridinium), an herbicide and model neurotoxicant, is identified to be one of the prime risk factors in Parkinson's disease (PD). In the Drosophila system, PQ is commonly used to measure acquired resistance against oxidative stress (PQ resistance test). Despite this, under acute PQ exposure, data on the oxidative stress response and associated impact on mitochondria among flies is limited. Accordingly, in this study, we measured markers of oxidative stress and mitochondrial dysfunctions among adult male flies (8-10 days old) exposed to varying concentrations of PQ (10, 20, and 40 mM in 5% sucrose solution) employing a conventional filter disc method for 24 h. PQ exposure resulted in significant elevation in the levels of oxidative stress biomarkers (malondialdehyde: 43% increase: hydroperoxide: 32-39% increase), with concomitant enhancement in reduced glutathione and total thiol levels in cytosol. Higher activity of antioxidant enzymes were also evident along with increased free iron levels. Furthermore, PQ exposure caused a concentration-dependent increase in mitochondrial superoxide generation and activity of manganese-superoxide dismutase (Mn-SOD). The activity levels of complex I-III, complex II-III, and Mg+2 adinosine triphosphatase (ATPase) were also decreased significantly. A robust diminution in the activity of succinate dehydrogenase and moderate decline in the citrate synthase activity suggested a specific effect on citric acid cycle enzymes. Collectively, these data suggest that acute PQ exposure causes significant oxidative stress and mitochondrial dysfunction among flies in vivo. It is suggested that in various experimental settings, while conducting the "PQ resistance stress test" incorporation of selected biochemical end points is likely to enhance the quality of the data.

Oxidant effects and toxicity of Croton campestris in Drosophila melanogaster

“…The increased activity of these enzymes could represent a compensatory response of cells in counteracting the pro-oxidant effect of plant components. Rotenone, a toxic alkaloid, increased ROS generation and toxic aldehydes in flies (Hosamani & Muralidhara 2013). Our group showed previously that D. furfuracea extract augmented ROS generation and modulated the activity of antioxidant enzymes in D. melanogaster (Pinho et al 2014).…”

“…PQ produces acutely (24-72 h) an enhanced generation of superoxides in mitochondrial fraction obtained from whole-body of flies exposed to PQ in vivo (Hosamani & Muralidhara 2013). Thus, a pro-oxidant effect of extract could be linked to the observed increment of PQ induced toxicity in flies.…”

PSTK is a novel gene associated with early lung injury in Paraquat Poisoning

“…At the molecular level, it has been shown that PQ exposure increases the activity of manganese-superoxide dismutase (Mn-SOD) and mitochondrial superoxide radicals. The activity levels of Mg+2 adenosine triphosphatase (ATPase) and complexes I-IIIand II-III were also lowered [5]. However, the molecular mechanisms underlying the pathogenesis of lung injury in PQ are yet to be elucidated.…”

Literature review and appraisal on alternative neurotoxicity testing methods

“…With respect to the number of citations there is high variability from year to year, but the high number of citations e.g. for 2004, 2008 and 2013 is rather due to few publications where multiple endpoints or compounds were simultaneously studied (Cole et al, 2004b;Rajini et al, 2008;Hosamani, 2013). The present document has been produced and adopted by the bodies identified above as authors.…”