Effects Of Rotenone Research Articles

Bougainvillea spectabilis flowers extract protects against the rotenone-induced toxicity.

To investigate the effect of two extracts of Bougainvillea spectabilis (B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection. Rotenone 1.5mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts (25mg or 50mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde (MDA), reduced glutathione, nitric oxide (nitrite), the pro-inflammatory cytokine interleukin-1beta (Il-1β) as well as butyrylcholinesterase, and paraoxonase-1 (PON-1) activities, were determined. Histopathology and caspase-3 immunohistochemistry were also performed. Rotenone resulted in significant increases of brain MDA (the product of lipid peroxidation), and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BChE activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BChE activity and increased brain Il-1β. When given to rotenone-treated rats, B. spectabilis extracts, however, decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract, however, caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain, liver and kidney damage caused by the toxicant. These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain, liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.

Rotenone Induced Alterations in Lifecycle Parameters and Compound Eye Morphology of Drosophila Melanogaster

Rotenone is a widely used natural pesticide and piscicide and a potent inhibitor of mitochondrial complex I (NADHquinone reductase) that elicits the degeneration of dopaminergic neurons. Present study explored the adverse effect of rotenone at concentrations far below the reported LC 50 on several life cycle parameters and on the compound eye structure of a non-target insect, Drosophila melanogaster . Newly hatched first instar larvae were introduced in Drosophila food medium containing different concentrations (50, 100, 150, 200, 250 μg/L) of rotenone. Different life cycle parameters were recorded. Emerged adult flies were collected and studied under Scanning electron microscope. Student's t-test was performed to explore significant difference and changes in both life cycle parameter and eye architecture. Treated groups showed significant delay (p<0.05 level) in larval duration, pupal duration, and in emergence of flies when compared with the control groups. Delay in life cycle parameters significantly increased with increase of rotenone exposure. Interestingly, the compound eye structure of the treated flies was seen to be affected by rotenone. Thus these results clearly demonstrate that chronic exposure to rotenone can alter the structure and lifecycle of a non-target organism like Drosophila at sub-lethal concentrations. Thus rotenone in Drosophila at sub-lethal concentrations might be the reason for developmental toxicity.

The effects of rotenone-induced toxicity via the NF-κB–iNOS pathway in rat liver

Rotenone has been used as a pesticide for many years, it is an environmental poison reported to cause neurological diseases. However, the effects of rotenone on the rat liver are unclear, as are the mechanisms of toxicity. In the present study, Sprague–Dawley (SD) rats were divided into five groups: control, dimethyl sulfoxide (DMSO), rotenone low-dose (1 mg/kg), rotenone mid-dose (2 mg/kg) and rotenone high-dose (4 mg/kg). The treatments were orally administered daily for 28 days, we assessed health status, mRNA expression levels of inflammatory factors, protein levels, nitric oxide (NO) content and histological changes. The results showed that body weight was significantly decreased in each rotenone group in a dose-dependent manner, compared with the control group. Rotenone significantly increased the mRNA levels of cyclooxygenase-2 (COX-2), nuclear factor kappaB (NF-κB), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF-α) in each rotenone group compared with the control group, except iNOS and TNF-α mRNA expression in the low-dose group. The protein levels of COX-2 were significantly higher in each rotenone group compared with the control group, NF-κB protein expression were significantly higher in the rotenone mid and high-dose groups, but not in the low-dose group, compared with the control group, similar changes were observed in NO content. Additionally, histological analysis revealed that the most severe tissue damage occurred in the high-dose group. These results indicated that rotenone has toxic effect in rat liver relating to inflammatory factors. Our findings provide insight into the mechanisms of rotenone hepatotoxicity.

Water-Soluble Coenzyme Q10 Reduces Rotenone-Induced Mitochondrial Fission.

Parkinson's disease is a neurodegenerative disorder characterized by mitochondrial dysfunction and oxidative stress. It is usually accompanied by an imbalance in mitochondrial dynamics and changes in mitochondrial morphology that are associated with impaired function. The objectives of this study were to identify the effects of rotenone, a drug known to mimic the pathophysiology of Parkinson's disease, on mitochondrial dynamics. Additionally, this study explored the protective effects of water-soluble Coenzyme Q10 (CoQ10) against rotenone-induced cytotoxicity in murine neuronal HT22 cells. Our results demonstrate that rotenone elevates protein expression of mitochondrial fission markers, Drp1 and Fis1, and causes an increase in mitochondrial fragmentation as evidenced through mitochondrial staining and morphological analysis. Water-soluble CoQ10 prevented mitochondrial dynamic imbalance by reducing Drp1 and Fis1 protein expression to pre-rotenone levels, as well as reducing rotenone treatment-associated mitochondrial fragmentation. Hence, water-soluble CoQ10 may have therapeutic potential in treating patients with Parkinson's disease.

Rotenone impairs hippocampal neuronal activity in a rat model of Parkinson’s disease

Parkinson’s disease (PD) is the most common neurodegenerative disease of unknown etiology and characterized by motor symptoms of tremor, rigidity, bradykinesia, and postural instability. Interactions between the dopaminergic systems and the hippocampus in synaptic plasticity and behavior are found. The rotenone-induced animal model is commonly used in research studies involved in PD. Administration of rotenone causes alterations of electrical neuronal activity. Rotenone (2.5 mg/kg/day) was administered intraperitoneally for 21 days to adult rats, and rotenone effects on rearing activity and electrophysiology were examined. Dose-dependent reduction of evoked neural activity and a reduction in firing strength were found in the hippocampus. Behaviorally, Rotenone rats showed a more consistent decrease in rearing across the 3 weeks, compared with animals in the control group. Thus, rotenone causes changes in hippocampal electrical activity and behavioral changes.

The effect of rotenone on the dopaminergic cells of the substantia nigra of the midbrain in the adult male albino rats

Background aims. Rotenone is a widely used insecticide has a neurodegenerative effect on the dopaminergic cells of substantia nigra (SN) of midbrain producing Parkinsonism. The aim of this study is to study the effects of rotenone when injected subcutaneously on the dopaminergic cells of the substantia nigra of the midbrain.Methods. The effects of rotenone on the SN of midbrain and the were determinedhistopathologically, immunohistochemically, and by transmission electron microscopy. Results. Subcutaneous rotenone produced Parkinsonism through producing degeneration of the dopaminergic cells of SN of the midbrain. Conclusion. These results indicate that, rotenone has a neurodegenerative effect on the dopaminergic cells of the substantia nigra of the midbrain producing parkinsonism

Effect of α-mangostin on Enhanced Transdermal Bioavailability of Gartanin via Efflux Transporters

Mangosteen (Garcinia mangostana L) is a tropical evergreen tree growing in Southeast Asia and has been used as traditional medicine treatment for skin wounds and infection. The pericarp crude extract can be isolated to fifty xanthone compounds, α-, β and γ-mangostins, gartanin etc. This study aimed to characterize and compare the transdermal transport of α-mangostin and gartanin when used alone and co-administered in human epidermal keratinocyte cells, neonatal (HEKn cells). The concentrations of the compounds were determined of by LC-MS/MS. In the absorptive direction, gartanin could not be detected during the entire 8 hour. Moreover, apparent permeability coefficient in secretory direction (Papp, B-A) was significantly higher than that of absorptive direction (Papp, A-B) but not found in α-mangostin. The results showed that after incubating the HEKn cells with rotenone, Papp, A-B of gartanin was significantly increased. In contrast, Papp, A-B of α-mangostin with and without rotenone was unchanged. For the mixture of gartanin and α-mangostin, α-mangostin had the similar inhibitory effect to the uptake and secretion of gartanin to the effect of rotenone. These indicated that the effect of efflux transporter of gartanin could be inhibited by α-mangostin and the permeability of gartanin in absorptive direction was achieved with co-administration of α-mangostin at high concentration. It is postulated that alpha-mangostin may act as a natural enhancer to improve the bioavailability of gartanin. The synergistic effect of the co-existing of the compounds in the natural extract may be important for therapy.

ER chaperone GRP78 regulates autophagy by modulation of p53 localization.

GRP78 (glucose regulated protein 78) is a major Endoplasmic Reticulum (ER) chaperone that plays a pivotal role in normal ER functioning. Its increased expression also works as an indicator of ER stress. Its anti-apoptotic and pro-autophagic activity makes it an intriguing target to study the relationship between GRP78 and p53, which is also a major regulator of apoptosis and autophagy. Here, we studied the effect of Rotenone and Parathion on human lung cancer cells (A549 cell line) specifically with respect to ER stress and its association with different cell death pathways. In our study, we observed that both compounds increase reactive oxygen species (ROS) generation, down regulate mitochondrial membrane potential (MMP) and affect DNA integrity. Our results indicate that Parathion causes ER stress, up regulates the expression of GRP78, leads to nuclear localization of p53 and induces autophagy while Rotenone down regulates GRP78, causes cytoplasmic localization of p53 and inhibits autophagy. Therefore, it may be concluded that GRP78 affects p53 localization which in turn regulates autophagy.

RNA-Seq Expression Analysis of Enteric Neuron Cells with Rotenone Treatment and Prediction of Regulated Pathways.

The enteric nervous system (ENS) is involved in the initiation and development of the pathological process of Parkinson's disease (PD). The effect of rotenone on the ENS may trigger the progression of PD through the central nervous system (CNS). In this study, we used RNA-sequencing (RNA-seq) analysis to examine differential expression genes (DEGs) and pathways induced by in vitro treatment of rotenone in the enteric nervous cells isolated from rats. We identified 45 up-regulated and 30 down-regulated genes. The functional categorization revealed that the DEGs were involved in the regulation of cell differentiation and development, response to various stimuli, and regulation of neurogenesis. In addition, the pathway and network analysis showed that the Mitogen Activated Protein Kinase (MAPK), Toll-like receptor, Wnt, and Ras signaling pathways were intensively involved in the effect of rotenone on the ENS. Additionally, the quantitative real-time polymerase chain reaction result for the selected seven DEGs matched those of the RNA-seq analysis. Our results present a significant step in the identification of DEGs and provide new insight into the progression of PD in the rotenone-induced model.

Does regional diversity recover after disturbance? A field experiment in constructed ponds.

The effects of disturbance on local species diversity have been well documented, but less recognized is the possibility that disturbances can alter diversity at regional spatial scales. Since regional diversity can dictate which species are available for recolonization of degraded sites, the loss of diversity at regional scales may impede the recovery of biodiversity following a disturbance. To examine this we used a chemical disturbance of rotenone, a piscicide commonly used for fish removal in aquatic habitats, on small fishless freshwater ponds. We focused on the non-target effects of rotenone on aquatic invertebrates with the goal of assessing biodiversity loss and recovery at both local (within-pond) and regional (across ponds) spatial scales. We found that rotenone caused significant, large, but short-term losses of species at both local and regional spatial scales. Using a null model of random extinction, we determined that species were selectively removed from communities relative to what would be expected if species loss occurred randomly. Despite this selective loss of biodiversity, species diversity at both local and regional spatial scales recovered to reference levels one year after the addition of rotenone. The rapid recovery of local and regional diversity in this study was surprising considering the large loss of regional species diversity, however many aquatic invertebrates disperse readily or have resting stages that may persist through disturbances. We emphasize the importance of considering spatial scale when quantifying the impacts of a disturbance on an ecosystem, as well as considering how regional species loss can influence recovery from disturbance.

Rotenone Decreases Hatching Success in Brine Shrimp Embryos by Blocking Development: Implications for Zooplankton Egg Banks.

While many zooplankton species recover quickly after the treatment of water resources with the piscicide, rotenone, some fail to reach pretreatment population density or, in rare cases, do not reappear at all. The variable impact of rotenone on zooplankton populations could stem from differences in the capacity of species to switch entirely to anaerobic catabolic pathways in the presence of rotenone, which blocks mitochondrial electron transport. Alternatively, variable responses among species could originate from differences in permeability of dormant life-stages to lipophilic chemicals like rotenone. The purpose of the present study was to determine the effects of rotenone on development, emergence and hatching of zooplankton embryos that lack both the anaerobic capacity to develop in the presence of rotenone and a permeability barrier to prevent the entry of rotenone during dormancy. Post-diapause embryos of the brine shrimp, Artemia franciscana, were employed as a model system, because they are permeable to lipophilic compounds when dechorionated and require aerobic conditions to support development. Early development in this species is also well characterized in the literature. Brine shrimp embryos were exposed to rotenone while development was either slowed by chilling or suspended by anoxia. Development, emergence and hatching were then observed in rotenone-free artificial seawater. The data presented demonstrate that rotenone freely diffuses across the embryonic cuticle in a matter of hours, and prevents development and emergence after brief exposures to ecologically relevant concentrations (0.025–0.5 mg L-1) of the piscicide. Neither the removal of rotenone from the environment, nor the removal of embryonic water with a hypertonic solution, are sufficient to reverse this block on development and emergence. These data indicate that rotenone could impair recruitment from egg banks for species of zooplankton that lack both an embryonic barrier to the entry of lipophilic compounds and the anaerobic capacity to develop when NADH:ubiquinone oxidoreductase activity is inhibited by rotenone.

Mitochondrial nitric oxide production supported by reverse electron transfer

Heart phosphorylating electron transfer particles (ETPH) produced NO at 1.2 ± 0.1 nmol NO. min−1 mg protein−1 by the mtNOS catalyzed reaction. These particles showed a NAD+ reductase activity of 64 ± 3 nmol min−1 mg protein−1 sustained by reverse electron transfer (RET) at expenses of ATP and succinate. The same particles, without NADPH and in conditions of RET produced 0.97 ± 0.07 nmol NO. min−1 mg protein−1. Rotenone inhibited NO production supported by RET measured in ETPH and in coupled mitochondria, but did not reduce the activity of recombinant nNOS, indicating that the inhibitory effect of rotenone on NO production is due to an electron flow inhibition and not to a direct action on mtNOS structure. NO production sustained by RET corresponds to 20% of the total amount of NO released from heart coupled mitochondria. A mitochondrial fraction enriched in complex I produced 1.7 ± 0.2 nmol NO. min−1 mg protein−1 and reacted with anti-75 kDa complex I subunit and anti-nNOS antibodies, suggesting that complex I and mtNOS are located contiguously. These data show that mitochondrial NO production can be supported by RET, and suggest that mtNOS is next to complex I, reaffirming the idea of a functional association between these proteins.

Anthocyanins protect from complex I inhibition and APPswe mutation through modulation of the mitochondrial fission/fusion pathways

Anthocyanins are a distinguished class of flavonoids with powerful free radical-scavenging activity that have been suggested as chemotherapeutic agents for the prevention of Alzheimer disease (AD). In this study, we examined the ability of nutraceutical Medox rich in purified cyanidin 3-O-glucoside (C3G), 3-O-b-glucosides and delphinidin 3-O-glucoside (D3G) to counteract mitochondrial deficiency induced by complex I inhibition and/or amyloid-β peptide (Aβ) induced toxicity. SH-SY5Y neuroblastoma cells were stably transfected with APP Swedish K670N/M671L double mutation (APPswe) or with the empty vector and treated with rotenone. We report that Medox treatment improves the metabolic activity and maintains cell integrity in both cell lines. At the mitochondrial level, APPswe and rotenone induced mitochondrial fragmentation, an effect that was counteracted by Medox through the modulation of fission and fusion proteins, resulting in a reshaped mitochondrial network. Although Medox was unable to fully neutralise the effects of rotenone on ATP levels and mitochondrial membrane potential, it was able to prevent rotenone-induced cytotoxicity.Our findings suggest that Medox anthocyanins, on top of their antioxidant capacity, ameliorate mitochondrial dysfunction generated by Aβ overproduction or by chemical inhibition of mitochondrial complex I via stabilization of the fusion/fission processes. Modulation of the mitochondrial network has been suggested as a novel therapeutic approach in diseases involving mitochondrial dysfunction and oxidative stress. Hence, increasing the understanding of how anthocyanins influence mitochondrial dynamics in a neurodegenerative context, could be of future therapeutic value.

Inhibition of mitochondrial complex-1 restores the downregulation of aquaporins in obstructive nephropathy.

Obstructive kidney disease is a common complication in the clinic. Downregulation of aquaporins (AQPs) in obstructed kidneys has been thought as a key factor leading to the polyuria and impairment of urine-concentrating capability after the release of kidney obstruction. The present study was to investigate the role of mitochondrial complex-1 in modulating AQPs in obstructive nephropathy. Following 7-day unilateral ureteral obstruction (UUO), AQP1, AQP2, AQP3, and vasopressin 2 (V2) receptor were remarkably reduced as determined by qRT-PCR and/or Western blotting. Notably, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of AQP1, AQP2, AQP3, and V2 In contrast, AQP4 was not affected by kidney obstruction or rotenone treatment. In a separate study, rotenone also attenuated AQPs' downregulation after 48-h UUO. To study the potential mechanisms in mediating the rotenone effects on AQPs, we examined the regulation of the COX-2/microsomal prostaglandin E synthase (mPGES)-1/PGE2/EP pathway and found that COX-2, mPGES-1, and renal PGE2 content were all significantly elevated in obstructive kidneys, which was not affected by rotenone treatment. For EP receptors, EP2 and EP4 but not EP1 and EP3 were upregulated in obstructive kidneys. Importantly, rotenone strikingly suppressed EP1 and EP4 but not EP2 and EP3 receptors. However, treatment of EP1 antagonist SC-51322 could not affect AQPs' reduction in obstructed kidneys. Collectively, these findings suggested an important role of mitochondrial dysfunction in modulating AQPs and V2 receptor in obstructive nephropathy possibly via prostaglandin-independent mechanisms.

The prevention of saltwater algal pond contamination using the electron transport chain disruptor, rotenone

Rotenone is a classic inhibitor of Complex I of the electron transport chain which is common to all life. Algae are known to be rotenone-insensitive because in addition to Complex I they have alternative pathways for the oxidation of NADH2. It is this differential sensitivity to rotenone that can be exploited to reduce many types of predators while not affecting biodiesel-producing algae. A universal tool like rotenone is needed to reduce predation in open ponds as predation is well known to limit cultivation to a few weeks in the warmer months. In this study, we tested the effect of rotenone on the mortality and reproduction of two marine algae strains, Nannochloropsis oculata and Tetraselmis suecica, and two marine rotifer strains, Brachionus manjavacas and Brachionus rotundiformis. The LC50s for the two rotifers ranged from 0.18 to 0.35μM while N. oculata was unaffected to at least 7.6μM. Rotifer reproduction was reduced at rotenone concentrations lower than those that caused mortality. Rotenone applications to produce 1 million gallons of biodiesel in one year are estimated to cost $1684. This provides algae farmers an important and inexpensive tool to manage grazing predators in algae mass cultures and avoid pond crashes.

A combined approach against tumorigenesis using glucose deprivation and mitochondrial complex 1 inhibition by rotenone.

Cancer cells exhibit various degrees of mitochondrial metabolic alterations. Owing to their multiple roles, mitochondria are attractive target for cancer therapy. Cancerous cells have high glucose (HG) requirements for their growth. Depriving them of glucose has been an approach used in many studies to restrict their perpetuation. However, such deprivation can negatively affect the surrounding normal cells in vivo. Keeping this in view, we treated HeLa cells with only physiological glucose (PG, 5.5 mM) and a combination of physiological glucose with a very low dose (1 nM) of rotenone (PGT), taking high glucose (HG, 25 mM)-treated HeLa cells as normal. We demonstrated that HeLa cells under PG condition mainly exhibited growth arrest. The PGT combination induced apoptosis in HeLa cells by generation of ROS, decrease in ATP production even with around 1.89-fold increase in glucose consumption, cell cycle arrest at S-phase and substantial increase in sub-diploid (Sub-D) population. The oxidative stress generated in both PG and PGT conditions stabilised p53 by localising it in the nuclei of HeLa cells, which would have otherwise undergone HPV-mediated inactivation. Pre-mature senescence induced due to limited glucose availability was found to be regulated by nuclear translocated p53 which, in turn, induced p21, pAkt and pERK. The cyto-toxic effect of rotenone on glucose deprived HeLa cells, synergistically activated NFκB, caspase-3 and Bax along with reduced expression of hyaluronan, a ROS scavenging molecule on their cell surface. Thus, our finding might be a valuable approach to specifically target cancerous cells in a more physiologically feasible condition and can serve as a relevant biochemical basis to gain new insights into cancer therapy.

Rotenone down-regulates HSPA8/hsc70 chaperone protein in vitro: A new possible toxic mechanism contributing to Parkinson’s disease

HSPA8/hsc70 (70-kDa heat shock cognate) chaperone protein exerts multiple protective roles. Beside its ability to confer to the cells a generic resistance against several metabolic stresses, it is also involved in at least two critical processes whose activity is essential in preventing Parkinson’s disease (PD) pathology. Actually, hsc70 protein acts as the main carrier of chaperone-mediated autophagy (CMA), a selective catabolic pathway for alpha-synuclein, the main pathogenic protein that accumulates in degenerating dopaminergic neurons in PD. Furthermore, hsc70 efficiently fragments alpha-synuclein fibrils in vitro and promotes depolymerization into non-toxic alpha-synuclein monomers.Considering that the mitochondrial complex I inhibitor rotenone, used to generate PD animal models, induces alpha-synuclein aggregation, this study was designed in order to verify whether rotenone exposure leads to hsc70 alteration possibly contributing to alpha-synuclein aggregation. To this aim, human SH-SY5Y neuroblastoma cells were treated with rotenone and hsc70 mRNA and protein expression were assessed; the effect of rotenone on hsc70 was compared with that exerted by hydrogen peroxide, a generic oxidative stress donor with no inhibitory activity on mitochondrial complex I. Furthermore, the effect of rotenone on hsc70 was verified in primary mouse cortical neurons. The possible contribution of macroautophagy to rotenone-induced hsc70 modulation was explored and the influence of hsc70 gene silencing on neurotoxicity was assessed. We demonstrated that rotenone, but not hydrogen peroxide, induced a significant reduction of hsc70 mRNA and protein expression. We also observed that the toxic effect of rotenone on alpha-synuclein levels was amplified when macroautophagy was inhibited, although rotenone-induced hsc70 reduction was independent from macroautophagy. Finally, we demonstrated that hsc70 gene silencing up-regulated alpha-synuclein mRNA and protein levels without affecting cell viability and without altering rotenone- and hydrogen peroxide-induced cytotoxicity.These findings demonstrate the existence of a novel mechanism of rotenone toxicity mediated by hsc70 and indicate that dysfunction of both CMA and macroautophagy can synergistically exacerbate alpha-synuclein toxicity, suggesting that hsc70 up-regulation may represent a valuable therapeutic strategy for PD.

Adenosine A2A Receptor Blockade Prevents Rotenone-Induced Motor Impairment in a Rat Model of Parkinsonism.

Pharmacological studies implicate the blockade of adenosine receptorsas an effective strategy for reducing Parkinson’s disease (PD) symptoms. The objective of this study is to elucidate the possible protective effects of ZM241385 and 8-cyclopentyl-1, 3-dipropylxanthine, two selective A2A and A1 receptor antagonists, on a rotenone rat model of PD. Rats were split into four groups: vehicle control (1 ml/kg/48 h), rotenone (1.5 mg/kg/48 h, s.c.), ZM241385 (3.3 mg/kg/day, i.p) and 8-cyclopentyl-1, 3-dipropylxanthine (5 mg/kg/day, i.p). After that, animals were subjected to behavioral (stride length and grid walking) and biochemical (measuring concentration of dopamine levels using high performance liquid chromatography, HPLC). In the rotenone group, rats displayed a reduced motor activity and disturbed movement coordination in the behavioral tests and a decreased dopamine concentration as foundby HPLC. The effect of rotenone was partially prevented in the ZM241385 group, but not with 8-cyclopentyl-1,3-dipropylxanthine administration. The administration of ZM241385 improved motor function and movement coordination (partial increase of stride length and partial decrease in the number of foot slips) and an increase in dopamine concentration in the rotenone-injected rats. However, the 8-cyclopentyl-1,3-dipropylxanthine and rotenone groups were not significantly different. These results indicate that selective A2A receptor blockade by ZM241385, but not A1 receptor blockadeby 8-cyclopentyl-1,3-dipropylxanthine, may treat PD motor symptoms. This reinforces the potential use of A2A receptor antagonists as a treatment strategy for PD patients.

An Assessment of the Effect of Rotenone on Selected Non-Target Aquatic Fauna.

Rotenone, a naturally occurring ketone, is widely employed for the management of invasive fish species. The use of rotenone poses serious challenges to conservation practitioners due to its impacts on non-target organisms including amphibians and macroinvertebrates. Using laboratory studies, we investigated the effects of different rotenone concentrations (0, 12.5, 25, 37.5, 50, 100 μg L-1) on selected invertebrate groups; Aeshnidae, Belostomatids, Decapods, Ephemeroptera, Pulmonata and zooplankton over a period of 18 hours. Based on field observations and body size, we hypothesized that Ephemeropterans and zooplankton would be more susceptible to rotenone than Decapods, Belostomatids and snails. Experimental results supported this hypothesis and mortality and behaviour effects varied considerably between taxa, ranging from no effect (crab Potamonuates sidneyi) to 100% mortality (Daphnia pulex and Paradiaptomus lamellatus). Planktonic invertebrates were particularly sensitive to rotenone even at very low concentrations. Future research should investigate the recovery time of invertebrate communities after the application of rotenone and conduct field assessments assessing the longer term effects of rotenone exposure on the population dynamics of those less sensitive organisms.

Hormetic effect of rotenone in primary human fibroblasts.

BackgroundRotenone inhibits the electron transfer from complex I to ubiquinone, in this way interfering with the electron transport chain in mitochondria. This chain of events induces increased levels of intracellular reactive oxygen species, which in turn can contribute to acceleration of telomere shortening and induction of DNA damage, ultimately resulting in aging. In this study, we investigated the effect of rotenone treatment in human fibroblast strains.ResultsFor the first time we here describe that rotenone treatment induced a hormetic effect in human fibroblast strains. We identified a number of genes which were commonly differentially regulated due to low dose rotenone treatment in fibroblasts independent of their cell origin. However, these genes were not among the most strongly differentially regulated genes in the fibroblast strains on treatment with rotenone. Thus, if there is a common hormesis regulation, it is superimposed by cell strain specific individual responses. We found the rotenone induced differential regulation of pathways common between the two fibroblast strains, being weaker than the pathways individually regulated in the single fibroblast cell strains. Furthermore, within the common pathways different genes were responsible for this different regulation. Thus, rotenone induced hormesis was related to a weak pathway signal, superimposed by a stronger individual cellular response, a situation as found for the differentially expressed genes.ConclusionWe found that the concept of hormesis also applies to in vitro aging of primary human fibroblasts. However, in depth analysis of the genes as well as the pathways differentially regulated due to rotenone treatment revealed cellular hormesis being related to weak signals which are superimposed by stronger individual cell-internal responses. This would explain that in general hormesis is a small effect. Our data indicate that the observed hormetic phenotype does not result from a specific strong well-defined gene or pathway regulation but from weak common cellular processes induced by low levels of reactive oxygen species. This conclusion also holds when comparing our results with those obtained for C. elegans in which the same low dose rotenone level induced a life span extending, thus hormetic effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-015-0038-8) contains supplementary material, which is available to authorized users.