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.
While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground. Increased virulence was also observed in bacteria that were grown in simulated microgravity conditions on the ground using the rotating wall vessel. Increased virulence of the space-flown bacteria was similar in magnitude between wild-type flies and those that were mutants for the well-characterized immune pathways Imd and Toll, suggesting that changes to the host immune system after infection are likely not a major factor contributing towards increased susceptibility of ground-reared flies infected with space-flown bacteria. Characterization of the bacteria shows that at later timepoints spaceflight bacteria grew at a greater rate than ground controls in vitro, and in the host. These results suggest complex physiological changes occurring in pathogenic bacteria in space environments, and there may be novel mechanisms mediating these physiological effects that need to be characterized.
Creatine (Cr), an ergogenic nutritional supplement is demonstrated to possess bioenergetic, antiexcitotoxic and antioxidant properties. This study investigated the neuroprotective effects of Cr against rotenone induced oxidative stress, mortality and neurotoxicty in Drosophila melanogaster. We found significant diminution in the endogenous levels of oxidative markers in whole body homogenates of flies exposed to Cr (2-10 mM). Cr supplementation resulted in reduced mortality in flies exposed to rotenone (500 microM) and better performance in a negative geotaxis assay. Further Cr (10 mM) markedly offset rotenone induced mitochondrial oxidative stress, completely restored the GSH levels, nitric oxide levels, activity of Mn-SOD and dopamine depletion. In an oxidative stress bioassay, flies given Cr prophylaxis exhibited marked resistance to paraquat exposure. These data allow us to hypothesize that the neuroprotective action of Cr in Drosophila may be related to its direct antioxidant activity and ability to abrogate rotenone induced mitochondrial oxidative stress.
Based on these findings, we infer that BM prophylaxis renders the brain resistant to PQ-mediated oxidative perturbations and thus may be better exploited as a preventive approach to protect against oxidative-mediated neuronal dysfunctions.
While the usage of Centella asiatica (CA) is on the increase worldwide, evidence demonstrating its protective efficacy against neurotoxicants is scarce. Hence the present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of CA against 3-nitropropionic-acid(3-NPA)-induced oxidative stress in the brain of prepubertal mice. We assessed the degree of oxidative stress in cytoplasm of brain regions of male mice (4 wk- old) given CA prophylaxis (5 mg/kg bw) for 10 days followed by 3-NPA administration (i.p.75 mg/kg bw) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the brain of untreated mice as evident by enhanced malondialdehyde levels, reactive oxygen species (ROS) generation, hydroperoxides and protein carbonyls (a measure of protein oxidation) in striatum and other regions (cortex, cerebellum and hippocampus), while CA prophylaxis completely ameliorated the 3-NPA- induced oxidative stress. Depletion of glutathione (GSH) levels, total thiols, perturbations in antioxidant enzymes and cholinergic enzymes in brain discernible among 3-NPA-treated mice were predominantly restored to normalcy with CA prophylaxis. It is hypothesized that the prophylactic protection offered by CA extract against neurotoxicant exposure may be largely due to its ability to enhance GSH, thiols and antioxidant defenses in the brain of prepubertal mice.
Background:
Parkinson’s Disease (PD) is characterized by alterations in cerebellum and
basal ganglia functioning with corresponding motor deficits and neuropsychiatric symptoms. Involvement
of oxidative dysfunction has been implicated for the progression of PD, and environmental
neurotoxin exposure could influence such behavior and psychiatric pathology. Assessing dietary
supplementation strategies with naturally occurring phytochemicals to reduce behavioral anomalies
associated with neurotoxin exposure would have major clinical importance. The present investigation
assessed the influence of Bacopa monneri (BM) on behaviors considered to reflect anxiety-like state
and motor function as well as selected biochemical changes in brain regions of mice chronically exposed
to ecologically relevant herbicide, paraquat (PQ).
Materials & Methods:
Male mice (4-week old, Swiss) were daily provided with oral supplements of
standardized BM extract (200 mg/kg body weight/day; 3 weeks) and PQ (10 mg/kg, i.p. three times a
week; 3 weeks).
Results:
We found that BM supplementation significantly reversed the PQ-induced reduction of exploratory
behavior, gait abnormalities (stride length and mismatch of paw placement) and motor impairment
(rotarod performance). In a separate study, BM administration prevented the reduction in
dopamine levels and reversed cholinergic activity in brain regions important for motor (striatum) pathology.
Further, in mitochondria, PQ-induced decrease in succinate dehydrogenase (SDH) activity
and energy charge (MTT reduction), was restored with BM supplementation.
Conclusion:
These findings suggest that BM supplementation mitigates paraquat-induced behavioral
deficits and brain oxidative stress in mice. However, further investigations would enable us to identify
specific molecular mechanism by which BM influences behavioural pathology.
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