Search

Rotenone is a pesticide that causes complex I inhibition and is widely known to induce motor disability and experimental Parkinson's disease (PD) in rodents. Evidence suggests a crucial role for sirtuin/nuclear factor-kappaB/nod-like receptor family, pyrin domain-containing 3 (SIRT1/NFκB/NLRP3) signaling and inflammation in PD and rotenone neurotoxicity. Hesperetin (C16H14O6) is a citrus flavonoid with documented anti-inflammatory activity. We investigated the value of hesperetin in delaying rotenone-induced PD in mice and the possible modulation of inflammatory burden. PD was induced in mice via rotenone injections. Groups were assigned as a vehicle, PD, or PD + hesperetin (50 or 100 mg/kg) and compared for the motor function, protein level (by ELISA), and gene expression (by real-time PCR) of the target proteins, histopathology, and immunohistochemistry for tyrosine hydroxylase enzyme. Hesperetin (50 or 100 mg/kg) alleviated the motor disability and the striatal dopamine level and decreased the expression of NLRP3 and NF-κB but increased SIRT1 expression (p < 0.05). Further, it enhanced the neural viability and significantly decreased neural degeneration in the substantia nigra, hippocampus, and cerebral cortex (p < 0.05). Taken together, we propose that hesperetin mediates its neuroprotective function via alleviating modulation of the SIRT1/NFκB/NLRP3 pathway. Therefore, hesperetin might delay the PD progression. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a second most common neurodegenerative disorder characterized by the selective and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rotenone is a neurotoxin which selectively degenerate dopaminergic neurons in striatum, leading to cause PD like symptoms. Rotenone was administered at a dose of 1.5 mg/kg, i.p. from day 1 to day 40. Treatment with doxycycline (50 and 100 mg/kg, p.o), tocopherol (5 mg and 10 mg/kg, p.o) alone, doxycycline (50 mg/kg, p.o) in combination with tocopherol (10 mg/kg, p.o), and ropinirole (0.5 mg/kg, i.p.) was given for 40 days 1 h prior to administration of rotenone. All behavioral parameters were analyzed on weekly basis. On day 41, animals were sacrificed and the striatum region was isolated for neurotransmitters estimation (dopamine, serotonin, norepinephrine, GABA and glutamate), biochemical analysis (GSH, nitrite, LPO, mitochondrial complexes I and IV), inflammatory markers estimation (IL-6, IL-1β and TNF-α) and activity of MAO-A, MAO-B. Doxycycline and tocopherol in combination significantly attenuated behavioral, neurotransmitters and biochemical alterations induced by rotenone in experimental rats as compared to alone treatment with DOX and TOCO. Similarly, DOX and TOCO combination significantly reduced the level of inflammatory markers, prevented the biochemical changes, decreased MAO-A and MAO-B and improved complex-I, complex-IV, cAMP levels significantly. The current study revealed that a combination of doxycycline with tocopherol contributed to the prevention of PD like symptoms in rats by antioxidant, anti-inflammatory, MAO inhibitory and neuromodulatory mechanisms. [ABSTRACT FROM AUTHOR]

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3–4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster. [ABSTRACT FROM AUTHOR]

Beaulieu J, Yates MC, Astorg L, Trépanier-Leroux D, Jeon H, Rudko SP, Humphries S, Fraser DJ, Cristescu ME, Derry AM. 2024. Environmental DNA for assessing impact and recovery of aquatic communities in an invaded mountain lake. Lake Reserv Manage. 40:111–131. The eradication of invasive species and associated side effects that influence the reestablishment of biological communities is a major challenge for conservation management of invaded ecosystems. We present a before-and-after-disturbance whole lake manipulation study from a high-elevation mountain lake in which we applied a 2-pronged approach to environmental DNA (eDNA) for assessing (1) impact and recovery of aquatic communities to the chemical eradication of invasive brook trout (Salvelinus fontinalis) and (2) the success of chemical eradication of the invasive fish. Using 18S and cytochrome oxidase I (COI) eDNA metabarcoding, we contribute to a paucity of literature that has comprehensively addressed nontarget effects of rotenone for invasive fish eradication on aquatic communities. We found that key trophic groups (phytoplankton, fungi, zooplankton, and macroinvertebrates) changed in community composition in response to rotenone applications. Fungi and macroinvertebrates, but not zooplankton and phytoplankton, reverted back toward pre-rotenone communities over the time scale of 2 yr. However, COI failed to detect several key species for food web reestablishment that were detected using physical specimen collection, likely due to low primer efficiency. We also found that quantitative polymerase chain reaction (qPCR), using species-specific primers, was effective for detecting brook trout presence/absence, although strong eDNA signals likely produced from carcasses in the ecosystem limited the utility of eDNA immediately following rotenone treatment. We provide specific recommendations for lake managers for the future application of eDNA approaches to monitor invasive fish eradication efforts and nontarget community effects for lake ecosystem restoration. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is often accompanied by depression, which may appear before motor signs. Oleanolic acid (OA), a pentacyclic triterpenoid substance, have many pharmacological properties. However, its efficacy in treating PD-related chronic unpredictable stress (CUS) is unknown. Our study used behavioral, biochemical, and immunohistochemical techniques to assess how OA affected PDrelated CUS. Rotenone (1 mg/kg i.p. for first 21 days) was used to induce Parkinsonism, and modest psychological & environmental stresses generated CUS (from day 22 to day 43) in animals. The study included daily i.p.administration of OA (5, 10, and 20 mg/kg) from day 1 to day 57 in male swiss albino mice. Animals were evaluated for behavioral, biochemical parameters, neurotransmitters, and immunohistochemical expression following the treatment. Results of the study revealed that treatment with OA at all doses alleviated the core symptoms of CUS linked to PD and improved motor and non-motor function. OA therapy significantly lowered IL-1β, TNF-α (p < 0.01, < 0.01, < 0.001), IL-6 (p < 0.05, < 0.01, < 0.001), oxidative stress (p < 0.05, < 0.01, < 0.01), and elevated norepinephrine (p < 0.05, < 0.01, < 0.01), dopamine, and serotonin (p < 0.05, < 0.01, < 0.001) levels. Moreover, OA therapy substantially reduced α-synuclein (p < 0.05, < 0.01, < 0.01) aggregation and increased BDNF (p < 0.05, < 0.01, < 0.001) & Nrf-2 (p < 0.05, < 0.01, < 0.01) levels, which boosts neuronal dopamine survival. The study's findings indicated that OA ameliorates depressive-like behavior persuaded by CUS in PD, decreases neuroinflammation, and improves neurotransmitter concentration via activating Nrf2-BDNF-dopaminergic pathway. Oleanolic acid reversed the CUS-induced depressive behaviors in Parkinson's disease Oleanolic acid alleviated oxidative stress, neuroinflammation, and improved brain neurotransmitter concentration Oleanolic acid reduced the α-synuclein aggregation and activated Nrf2-BDNF-dopaminergic signaling pathways to ameliorate motor and depressive behaviors in parkinsonian mice [ABSTRACT FROM AUTHOR]

AbstractAimMaterial and MethodsResultsConclusionThe current investigation’s goals are to pharmacologically evaluate the neurotherapeutic role of the bioactive compound Alpha Pinene (ALP)-loaded Self-emulsifying nano-formulation (SENF) in neurotoxin (Rotenone and the Industrial Solvent Trichloroethylene)- induced dopaminergic loss. It is believed that these models simulate important aspects of the molecular pathogenesis of Parkinson’s disease.The ALP-nano-formulation’s anti-Parkinson’s activity was compared to ALP suspension in Wistar rats after rotenone and trichloro ethylene-induced dopaminergic loss. Neurobehavioral and motor performances were measured on the 14th, 21st, and 28th day in the rotenone model. However, in the trichloroethylene model, it was measured from the 4th to the 8th week.Significant neurobehavioral improvement has been found in ALP-SENF treated animals then untreated and animals treated with plain ALP suspension. Furthermore, biochemical tests reveal marked expression of catalase, glutathione, and superoxide dismutase, which significantly combat the (Oxidative stress) OS-induced neurodegeneration.The antioxidant effect of ALP-SENF likely includes free radicals neutralization and the activation of enzymes associated with antioxidant activity, leading to the enhancement of neurobehavioral abnormalities caused by rotenone and trichloroethylene. [ABSTRACT FROM AUTHOR]

Environmental toxins are known to be one of the important factors in the development of Parkinson's disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT). A total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates. Rats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity. Findings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigral dopaminergic neurons, leading to reduced motor control. A contributing factor for the nigrostriatal degeneration is known to be oxidative stress, while antioxidant/anti-inflammatory properties of natural polyphenols have been suggested to show beneficial effects. The present study questioned the potential neuroprotective effects of supplementary diet with Corinthian currant, using a rat rotenone PD model. The alterations in motor activity, brain Corinthian currant polar phenols' accumulation, expression patterns of tyrosine hydroxylase (TH), dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF) in the nigrostriatal dopaminergic system were determined in rotenone-treated, currant-diet rats and matching controls. Rotenone treatment resulted in motor deficits and TH expression decreases in the nigrostriatal pathway, exhibiting PD-like behavioural motor and neurochemical phenotypes. Interestingly, 38 days Corinthian currant consumption resulted in differential accumulation of polar phenols in mesencephalon and striatum and had a significant effect on attenuating motor deficits and dopaminergic cell loss in substantia nigra pars compacta. In addition, it induced up-regulation of BDNF expression in the nigrostriatal dopaminergic system. Taken all together, evidence is provided for the potential neuroprotective influences of Corinthian currant consumption, involving the neurotrophic factor BDNF, in rescuing aspects of PD-like phenotype. [ABSTRACT FROM AUTHOR]

Eilers J, Miller R, Loomis D, Vogel A. 2023. Effects of cyprinid removal and reintroduction: Diamond Lake, Oregon. Lake Reserv Manage. 39:156–173. Diamond Lake, located in the Oregon Cascade Range, was treated with rotenone in 2006 to remove invasive populations of cyprinids, Gila bicolor and Notemigonus crysoleucas. The treatment successfully removed all fish, and the lake was restocked in 2007 with rainbow trout (Oncorhynchus mykiss). The treatment resulted in large increases in transparency, large cladocerans (Daphnia pulicaria), and benthic invertebrates. The previous cyanobacterial blooms were comprised almost exclusively of Anabaena [Dolichospermum], whereas the current populations of cyanophytes include Gloeotrichia. Cyprinids were reintroduced into the lake and documented in 2008 (Notemigonus crysoleucas) and 2015 (Gila bicolor), likely contributing to a decline of several metrics of water quality. Piscivorous trout (Salmo trutta and Salmo trutta x Salvelinus fontinalis) were introduced into the lake starting in 2016 to control the introduced cyprinids. The cyprinid populations have stabilized, and most metrics of lake status (Secchi disk transparency, phytoplankton biovolume, abundance of large cladocerans, zoobenthic biomass, trout condition factor) indicate that the lake has improved substantially since the treatment and introduction of piscivorous trout. It is unclear whether the cyprinid populations are constrained by behavioral mechanisms associated with the introduction of the piscivorous trout or whether other factors currently keep the cyprinids in check. The success of this biomanipulation project requires continued monitoring and use of adaptive management strategies to respond to changes in fish composition. [ABSTRACT FROM AUTHOR]

This article discusses a case of rotenone poisoning caused by consuming Pachyrhizus erosus, also known as yam bean. The patient experienced symptoms such as dizziness, weakness, and vomiting after ingesting the plant. The diagnosis was made using DNA barcoding of the gastric contents combined with mass spectrometry. The article highlights the importance of molecular evidence in diagnosing plant poisoning when traditional methods are not available. The authors suggest that DNA barcoding could be a valuable tool in the field of clinical toxicology. [Extracted from the article]

As a pesticide extracted from plants, rotenone is widely used to control plant pests. In order to explore the safety of rotenone in the environment, we took 60 healthy male SD rats and randomly divided them into rotenone low-dose group, rotenone medium-dose group, rotenone high-dose group, dimethyl sulfoxide group (DMSO), and control group. After 28 days of oral administration, the rat liver tissue ultrastructure, liver function, oxidative stress indexs, mitochondrial function, and apoptosis-related factors were tested to evaluate the hepatotoxicity and toxicological mechanism of rotenone. The results showed that rotenone significantly increased the hepatic index of rats and the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. Rotenone can reduce the number of endoplasmic reticulum of hepatocyte, concentrate chromatin and make the hepatocyte nuclears irregular. Rotenone weakened the ATP synthesis ability in mitochondria, decreased the activity of ATP enzyme in mitochondria, and increased the mitochondrial membrane potential in the high-dose group. And it induced oxidative stress damage to the mitochondria of rat liver cells. Rotenone can upregulate the expression of pro-apoptotic factors and downregulate the expression of anti-apoptotic factors. These results indicate that oral rotenone in rats induced hepatotoxicity in a dose-dependent manner. The mechanism of rotenone poisoning is that oxidative stress damages organelles of hepatocyte such as mitochondria and endoplasmic reticulum, resulting in their function being weakened or lost, leading to hepatocyte apoptosis. [ABSTRACT FROM AUTHOR]

Rotenone is a broadly used organic pesticide with neurotoxicity as a serious side effect for non-target organisms. The inhibition of mitochondrial complex I is the principal mechanism of rotenone toxicity that leads to oxidative stress, apoptosis, and decreased autophagy. Several chemical compounds have been demonstrated to exhibit antioxidant, antiapoptotic, and autophagy enhancement in both in vitro and in vivo studies. Some chemical agents can ameliorate rotenone-induced neurotoxicity through their antioxidant, anti-inflammatory, and anti-apoptotic properties. They also inhibit the accumulation of α-synuclein, control dopamine release, affect ion channels, and induce autophagy. Clinical trials are essential to reinforce the effectiveness of any chemical in managing patients with rotenone neurotoxicity. [ABSTRACT FROM AUTHOR]

We have previously shown that low-intensity ultrasound (LIUS) can modulate mitochondrial complex I activity and the generation of mitochondrial reactive oxygen species (mtROS) in PC12 cells. This study investigated the mechanism of LIUS by comparing its effect on mitochondrial dysfunction by three different pathways. LIUS was shown to reverse the effects of rotenone, a Q-site blocker, on the complex I inhibition, mtROS generation, and drop of mitochondrial membrane potential (Δψm). In contrast, common antioxidants, N-acetyl cysteine (NAC), and uric acid (UA) blocked rotenone-induced mtROS generation and Δψm drop without recovering the complex I activity, which suggested that Δψm drop is correlated with mtROS generation rather than complex I inhibition itself. Ionomycin, an ionophore for Ca2+, and L-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, induced mtROS generation and Δψm drop without inhibiting complex I activity via different mechanisms. LIUS showed no effect on ionomycin-induced Δψm drop but showed partial inhibition on the other effects of ionomycin and BSO. These results suggest that LIUS might have redundant mechanisms but acted mainly on the complex I activity thereby modulating mtROS and Δψm levels. LIUS appeared to act on the Q-module of complex I because it showed no inhibitory effect on Zn2+, an inhibitor of the proton transporting P-module of complex I. Interestingly, pretreatment of LIUS for up to an hour in advance blocked the rotenone effect as efficiently as the co-treatment. Further studies are needed to reveal the exact mechanism of LIUS to inhibit complex I activity. [ABSTRACT FROM AUTHOR]

Oxidative stress is known to be involved in development of numerous diseases including cardiovascular, respiratory, renal, kidney and cancer. Thus, investigations that mimic oxidative stress in vitro may play an important role to find new strategies to control oxidative stress and subsequent consequences are important. Rotenone, widely used as a pesticide has been used as a model to simulate oxidative stress. However, this chemical was found to produce several diseases. Therefore, the aim of this study was to investigate the antioxidant and cytoprotective effect of avocado (Persea americana Mill) extract and oil in monkey kidney epithelial cells (VERO) exposed to rotenone. VERO cells were exposed to IC50 of rotenone in conjunction with different concentrations of avocado extract and oil (ranging from 1 to 1000 µg/ml), for 24 hr. Subsequently, cell viability and oxidative metabolism were assessed. Data demonstrated that avocado extract and oil in the presence of rotenone increased cellular viability at all tested concentrations compared to cells exposed only to rotenone. In addition, extract and avocado oil exhibited antioxidant action as evidenced by decreased levels of reactive oxygen species (ROS), superoxide ion, and lipid peroxidation, generated by rotenone. Further, avocado extract and oil appeared to be safe, since these compounds did not affect cell viability and or generate oxidative stress. Therefore, avocado appears to display a promising antioxidant potential by decreasing oxidative stress. [ABSTRACT FROM AUTHOR]

Beaulieu J, Trépanier-Leroux D, Fischer JM, Olson MH, Thibodeau S, Humphries S, Fraser DJ, Derry AM. 2021. Rotenone for exotic trout eradication: nontarget impacts on aquatic communities in a mountain lake. Lake Reserv Manage. 37:323–338. Rotenone is widely used in lake and reservoir management for the eradication of exotic fish. However, nontarget effects of rotenone on freshwater organisms such as zooplankton and macroinvertebrates are of concern because of the ecological importance of these organisms in aquatic food webs as a resource base for fish, especially when rotenone is applied to lakes prior to native fish reintroduction. The objective of our study was to determine the effects of rotenone on nontarget zooplankton and macroinvertebrate species assemblages in a headwater mountain lake where rotenone was applied to remove exotic brook trout (Salvelinus fontinalis; Banff, AB Canada). We found strong negative rotenone impacts on the community structure and density of crustacean zooplankton, and to a lesser extent on macroinvertebrates, lasting for at least 1 yr after the rotenone treatment. Our study offers 2 unique insights that differentiate from rotenone studies on other lakes: (1) the persistent and almost complete eradication of crustacean zooplankton in the following summers, 11 months after rotenone treatment, and (2) a considerable shift in the macroinvertebrate community composition, likely resulting from combined effects of both nontarget rotenone effects on taxon density and trophic interactions associated with the eradication of brook trout from the lake. We advocate that assisted recolonization in the restoration of aquatic food webs could play an important role in facilitating nontarget aquatic community recovery following lake rotenone treatment. [ABSTRACT FROM AUTHOR]

The anti-diabetic medicine metformin has been reported as an anti-ageing drug candidate as it mimics the benefits of caloric restriction and reduces ageing-related oxidative stress in various experimental organisms. We investigated the possible anti-oxidative role of metformin against rotenone-induced oxidative stress and cytotoxicity in erythrocytes of Wistar rats. Rotenone is a well-known inducer of oxidative stress which leads to a cellular redox imbalance. We have co-exposed the experimental rats with rotenone (2.5 mg/kg, i.p.) and metformin (300 mg/kg, orally) for 30 days to investigate the protective effects of metformin on various rotenone-induced impaired oxidative stress biomarkers in rat erythrocytes. We found that a significant alleviation in the levels of rotenone-induced pro-oxidant and anti-oxidant markers following exposure of metformin. Our findings suggest that metformin supplementation shows a protective role in against rotenone-induced redox imbalance and cytotoxicity in rat erythrocytes. [ABSTRACT FROM AUTHOR]

Oxidative stress plays an important role in the pathogenesis of Parkinson's disease (PD), particularly the inhibition of mitochondrial complex-I. This study aimed to evaluate the effect of fisetin in the rotenone-induced rat model of PD. Rotenone was administered (2 mg/kg s.c.) for 35 days to induce PD in animals. Fisetin was administered at two doses (10 mg/kg and 20 mg/kg p.o.) for 25 days to the animals that were given rotenone. Behavioral experiment, i.e. cylinder test, was performed to assess the motor asymmetry. Animals were euthanized, and mid brains were isolated for the estimation of tricarboxylic acid cycle enzymes, oxidative measures (lipid peroxidation (LPO), glutathione (GSH) and catalase) and complex-I activity. In addition, histopathological studies were conducted. Fisetin treatment improved motor function in the cylinder test and reversed the rotenone-induced changes in mitochondrial enzymes, striatal dopamine levels, antioxidant enzyme levels and histological changes. An important finding of this study was both the doses of fisetin significantly (p < 0.05) enhanced rotenone-induced behavioral and biochemical changes and the effects were found to be dose dependent. Based on the present results, we hypothesize that fisetin may improve the mitochondrial enzyme activity, thereby preventing the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a neurodegenerative disorder caused due to the degeneration of dopamine-releasing neurons. Mucunapruriens (MP) and Sesame oil (SO) are well-known for their neuroprotective and antioxidative properties but to date, no experimental study proves their synergistic effects in PD. The protective and therapeutic potential of MP extract containing 40% levodopa along with SO were evaluated, individually and together, on a multi-low dose (0.006 mg/g) of a rotenone-induced zebrafish model of PD. Neuroprotective roles of MP extract and SO on the activities of enzymatic and non-enzymatic antioxidants such as Catalase, GST, AChE, BChE, adenosine deaminase, and content of Glutathione and Malondialdehyde were examined. Also, the dopamine, TNF-α, and IL-1β levels were estimated via the ELISA method. Histopathological studies were performed for the confirmation of neuronal damage. Swiss Target Prediction software was used to predict the target protein receptors for MP and SO and protein interaction networks were used to decipher their role in molecular pathways such as synaptic plasticity, dopamine synthesis, etc. through Cytoscape and bingo plugin. The combination of MP extract and SO was observed to ameliorate oxidative stress and significantly increase the cholinergic enzyme activity and dopamine level and thereby helps in preventing neuronal cell damage. [ABSTRACT FROM AUTHOR]

Rotenone is a mitochondrial complex I inhibitor, which can cause the death of dopaminergic (DA) neurons and Parkinson's disease (PD). Currently, whether metformin has a protective effect on neurotoxicity induced by rotenone is unclear. The purpose of this study was to evaluate the potential protective effect of metformin against rotenone-induced neurotoxicity. PD animal model was established by unilateral rotenone injection into the right substantia nigra (SN) of C57BL/6 mice. The behavioral tests were performed by rotarod test and cylinder test. The numbers of TH-positive neurons and Iba-1 positive microglia in the SN were investigated by immunohistochemical staining. The mRNA levels of proinflammatory cytokines (TNF-α and IL-1β) and molecules involved in endoplasmic reticulum (ER) stress (ATF4, ATF6, XBP1, Grp78, and CHOP) in the midbrain were detected by Quantitative real-time PCR. This study showed that 50 mg/kg metformin given orally daily, beginning 3 d before rotenone injection and continuing for 4 weeks following rotenone injection, significantly ameliorated dyskinesia, increased the number of TH-positive neurons, and mitigated the activation of microglia in the SN in rotenone-induced PD mice. Furthermore, 50 mg/kg metformin markedly downregulated the expression of proinflammatory cytokines (TNF-α and IL-1β) and ER stress-related genes (ATF4, ATF6, XBP1, Grp78, and CHOP) in rotenone-induced PD mice. Metformin has a protective effect on DA neurons against rotenone-induced neurotoxicity through inhibiting neuroinflammation and ER stress in PD mouse model. [ABSTRACT FROM AUTHOR]

Rotenone, an environmental toxin, triggers Parkinson's disease (PD)-like pathology through microglia-mediated neuronal death. The effects and molecular mechanisms of flavonoid luteolin against rotenone-induced toxicity was assessed in microglial BV2 cells. Cells were pretreated with luteolin (1–50 µM) for 12 h and then was co-treated with 20 µM of rotenone for an additional 12 h in the presence of luteolin. The viability (MTT), IL-1β and TNF-α levels and lactate dehydrogenase (LDH) release (ELISA), and Park2, Lrrk2, Pink1, Nrf2 and Trx1 mRNA levels (qRT-PCR) were measured. In rotenone exposed microglia, luteolin increased viability significantly at lower concentrations (1–5 µM) compared to higher concentrations (25–50 µM). Rotenone increased LDH release and IL-1β levels in a dose-dependent manner (1–20 µM). Luteolin inhibited rotenone-induced LDH release, however the activity decreased in concentration-dependent manner Neither rotenone nor luteolin altered TNF-α levels, but luteolin reduced IL-1β levels in a concentration dependent manner in rotenone exposed cells. The mRNA levels of Nrf2 and Trx1, which are the master regulators of redox state, were increased by rotenone, as well as by luteolin, which exhibited an inverse relationship between its concentration and effect (1–20 µM). Park2 mRNA levels increased by luteolin, but decreased by rotenone. Pink1 mRNA levels was not altered by rotenone or luteolin. Lrrk2 mRNA levels reduced by luteolin, while it was increased by rotenone. Results suggest that luteolin have favorable effects on regulation of oxidative stress response, genes associated with PD and inflammatory pathways, hence protects microglia against rotenone toxicity in a hormetic manner. [ABSTRACT FROM AUTHOR]

**Therapeutic range: 129-2000 µg/L. The plasma rotenone concentration was relatively low compared to fatal cases, in whom concentrations have been as high as 72 µg/L [[2]]. Dear Editor, Rotenone is a naturally occurring piscicide and insecticide derived from plants such as yam bean ( I Pachyrhizus erosus) i , derris, and the Florida fish poison tree. [Extracted from the article]

Curcuma longa (Family, Zingiberaceae) is rich in polyphenolic compounds; curcuminoids which is used in traditional medicine as antioxidant, anti-tumor, antimicrobial, anti-inflammatory, wound healing, and gastroprotective agents. The aim of the present work is to optimize curcuminoids extraction from C. longa rhizomes using different solvents and evaluate its efficacy in rotenone-induced Parkinson's disease in rats. The biological evaluation was done referring to Sinemet (levodopa) as dopaminergic drug and the newly ZM241385 as non-dopaminergic agent. The highest extraction yield was found in methanol (74 % w/w of defatted powder) and acetone (65 % w/w of defatted powder) extracts, while the highest curcuminoids content (566 mg/g extract) was found in the ethyl acetate extract. High performance liquid chromatography (HPLC) analysis showed three major compounds; curcumin (68 %), demethoxycurcumin (19 %) and bisdemethoxycurcumin (11 %) of total curcuminoids. Rotenone induction caused disturbance in neurotransmitters, antioxidants, inflammatory and apoptotic markers, DNA fragmentation, adenosine A2A receptor gene expression, energy production markers and brain histological features. Treatments with ethyl acetate extract, Sinemet drug and ZM241385 enhanced the selected parameters by variable degrees. In conclusion, C. longa exerted anti-parkinsonism efficacy as compared to the classical Sinemet drug, while ZM241385 showed more therapeutic effect. As the plant extract improved DA and adenosine A2A gene expression levels, this shed the light on its role as a therapeutic dopaminergic agent and therefore its mode of action must be studied in details. [ABSTRACT FROM AUTHOR]

Aim of the study: Rotenone is a commonly used pesticide that inhibits complex I of the mitochondrial electron transport system. Rotenone exposed rats demonstrate many characteristics of Parkinson Disease (PD). Oxidative stress is one of the hallmarks of PD, being the major sources of ROS in the DA neurons. In recent years the strong connection between the intestinal environment and the function of the central nervous system (CNS) has gained widespread popularity. In order to explain the mechanism underlying the GI dysfunction in PD, we aimed to investigate oxidant-antioxidant status in the brain and intestine, as well as locomotor activity, in rotenone exposed zebrafish. Materials and methods: Adult zebrafish were exposed to 2 mg/L rotenone for 30 days. At the end of the experiment, locomotor activity was determined by simple observation. Lipid peroxidation (LPO), nitric oxide (NO) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in the homogenates. Results: Locomotor activity decreased in the rotenone exposed zebrafish. LPO increased in both brain and intestines whereas NO increased only in the brain. Decreased GST and CAT activities were found in both tissues whereas SOD activity decreased only in the intestines. Conclusion: As a conclusion, the results of our study support the connection between gut and brain axis in rotenone exposed zebrafish by means of oxidative stress and NO for the first time in literature. [ABSTRACT FROM AUTHOR]

Neuroinflammation and oxidative damage are the two main malfactors that play an important role in the pathogenesis of experimental and clinical Parkinson’s disease (PD). The current study was aimed to study the possible anti-oxidant and anti-inflammatory effects of the methanolic extract of Agaricus blazei (A. blazei) against rotenone-induced PD in mice. Male Albino mice were randomized and divided into the following groups: control, treated with rotenone (1 mg/kg/day), co-treated with rotenone and A. blazei (50, 100, and 200 mg/kg b.w.), and treated with A. blazei alone (200 mg/kg b.w.). After the end of the experimental period, behavioral studies, biochemical estimations, and protein expression patterns of inflammatory markers were studied. Rotenone treatment exhibited enhanced motor impairments, neurochemical deficits, oxidative stress, and inflammation, whereas oral administration of A. blazei extract attenuated the above-said indices. Even though further research is needed to prove its efficacy in clinical studies, the results of our study concluded that A. blazei extract offers a promising and new therapeutic lead for treatment of PD. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat kinase 2 (LRRK2) is involved in Parkinson’s disease (PD) pathology. A previous study showed that rotenone treatment induced apoptosis, mitochondrial damage, and nucleolar disruption via up-regulated LRRK2 kinase activity, and these effects were rescued by an LRRK2 kinase inhibitor. Heat-shock protein 70 (Hsp70) is an anti-oxidative stress chaperone, and overexpression of Hsp70 enhanced tolerance to rotenone. Nucleolin (NCL) is a component of the nucleolus; overexpression of NCL reduced cellular vulnerability to rotenone. Thus, we hypothesized that rotenone-induced LRRK2 activity would promote changes in neuronal Hsp70 and NCL expressions. Moreover, LRRK2 G2019S, the most prevalent LRRK2 pathogenic mutant with increased kinase activity, could induce changes in Hsp70 and NCL expression. Rotenone treatment of differentiated SH-SY5Y (dSY5Y) cells increased LRKK2 levels and kinase activity, including phospho-S935-LRRK2, phospho-S1292-LRRK2, and the phospho-moesin/moesin ratio, in a dose-dependent manner. Neuronal toxicity and the elevation of cleaved poly (ADP-ribose) polymerase, NCL, and Hsp70 were increased by rotenone. To validate the induction of NCL and Hsp70 expression in response to rotenone, cycloheximide (CHX), a protein synthesis blocker, was administered with rotenone. Post-rotenone increased NCL and Hsp70 expression was repressed by CHX; whereas, rotenone-induced kinase activity and apoptotic toxicity remained unchanged. Transient expression of G2019S in dSY5Y increased the NCL and Hsp70 levels, while administration of a kinase inhibitor diminished these changes. Similar results were observed in rat primary neurons after rotenone treatment or G2019S transfection. Brains from G2019S-transgenic mice also showed increased NCL and Hsp70 levels. Accordingly, LRRK2 kinase inhibition might prevent oxidative stress-mediated PD progression. Abbreviations: 6-OHDA: 6-hydroxydopamine; CHX: cycloheximide; dSY5Y: differentiated SH-SY5Y; g2019S tg: g2019S transgenic mouse; GSK/A-KI: GSK2578215A kinase inhibitor; HSP70: heat shock protein 70; LDH: lactose dehydrogenase; LRRK2: leucine rich-repeat kinase 2; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; myc-GS LRRK2: myc-tagged g2019S LRRK2; NCL: nucleolin; PARP: poly(ADP-ribose) polymerase; PD: Parkinson’s disease; PINK1: PTEN-induced putative kinase 1; pmoesin: phosphorylated moesin at t558; ROS: reactive oxygen species [ABSTRACT FROM AUTHOR]

The objectives of this study were to develop a robust protocol to measure the rate of hydrogen peroxide (H2O2) production in isolated perfused rat lungs, as an index of oxidative stress, and to determine the cellular sources of the measured H2O2 using the extracellular probe Amplex red (AR). AR was added to the recirculating perfusate in an isolated perfused rat lung. AR's highly fluorescent oxidation product resorufin was measured in the perfusate. Experiments were carried out without and with rotenone (complex I inhibitor), thenoyltrifluoroacetone (complex II inhibitor), antimycin A (complex III inhibitor), potassium cyanide (complex IV inhibitor), or diohenylene iodonium (inhibitor of flavin-containing enzymes, e.g. NAD(P)H oxidase or NOX) added to the perfusate. We also evaluated the effect of acute changes in oxygen (O2) concentration of ventilation gas on lung rate of H2O2 release into the perfusate. Baseline lung rate of H2O2 release was 8.45 ± 0.31 (SEM) nmol/min/g dry wt. Inhibiting mitochondrial complex II reduced this rate by 76%, and inhibiting flavin-containing enzymes reduced it by another 23%. Inhibiting complex I had a small (13%) effect on the rate, whereas inhibiting complex III had no effect. Inhibiting complex IV increased this rate by 310%. Increasing %O2 in the ventilation gas mixture from 15 to 95% had a small (27%) effect on this rate, and this O2-dependent increase was mostly nonmitochondrial. Results suggest complex II as a potentially important source and/or regulator of mitochondrial H2O2, and that most of acute hyperoxia-enhanced lung rate of H2O2 release is from nonmitochondrial rather than mitochondrial sources. [ABSTRACT FROM AUTHOR]

Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The ‘dual-hit’ hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this ‘dual-hit hypothesis’ and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1 week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD. [ABSTRACT FROM AUTHOR]

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H2O2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy. [ABSTRACT FROM AUTHOR]

Invasive fish eradication is a key management strategy in aquatic ecosystems, and is often accomplished using piscicides such as rotenone. However, the effects of piscicides on aquatic invertebrate communities are poorly understood, particularly over long time scales. We monitored invertebrate communities in two treatment and two reference streams prior to and for one year following the use of rotenone to eradicate trout in Zealandia wildlife sanctuary, Wellington. Immediately following treatment, invertebrate density and taxonomic richness declined significantly, and community composition diverged markedly relative to reference streams, with pollution sensitive taxa declining greater than more tolerant taxa. Treatment streams recovered to pre-treatment conditions within 4–12 months of rotenone application, indicating minor long-term impacts on invertebrate communities. Speed of recovery of individual taxa appeared to be associated with life history variables, e.g. generation times and dispersal ability. Untreated upstream reaches and nearby water bodies likely facilitated successful invertebrate community recovery. Our results demonstrate that rapid recovery of New Zealand stream invertebrate communities is possible within one year of rotenone application. [ABSTRACT FROM PUBLISHER]

Disorganized redox homeostasis is a main factor causing a number of diseases and it is imperative to comprehend the orchestration of circadian clock under oxidative stress in the organism, Drosophila melanogaster. This investigation analyses the influence of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-stimulated oxidative stress in fruit fly. The characteristics of rhythms of thiobarbituric acid reactive substances (TBARS), antioxidants (superoxide dismutase (SOD) and catalase (CAT)) were noticeably decreased in rotenone administered flies. Supplementation of hesperidin to rotenone-treated flies increased the mesor and modulated the amplitudes of antioxidants and conspicuously decreased the mesor values of TBARS. In addition, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin caused normalization of the altered rhythms. Disorganization of 24 h rhythms in markers of redox homeostasis was observed during rotenone treatment and the impairment is severe in circadian clock mutant (Cryb) flies. Reversibility of rhythms was prominent subsequent to hesperidin treatment in wild-type flies than (Cryb) flies. These observations denote a role of circadian clock in redox homeostasis and the use of Drosophila model in screening putative antioxidative phytomedicines prior to their usage in mammalian systems. [ABSTRACT FROM PUBLISHER]

The present study was aimed to find out the effect ofAgaricus blazeimushroom extract against rotenone-induced cellular model. SH-SY5Y neuroblastoma cells are divided into four experimental groups (control, rotenone (100 nM),A. blazei(5 μg/ml) + rotenone (100 nM), andA. blazeialone treated) based on MTT assay, cells were allowed to measure the ROS, TBARS levels, and antioxidants activities. Finally, mitochondrial transmembrane potential (MMP) and expressions of apoptotic proteins were also analyzed. Pre-treatment withA. blazeisignificantly enhanced cell viability, attenuated rotenone-induced ROS, MMP, and apoptosis. Our results indicated that anti-apoptotic properties of this natural compound due to its antioxidant and mitochondrial protective function protect rotenone-induced cytotoxicity. Therefore, it may be concluded thatA. blazeican be further developed as a promising drug for the treatment of Parkinson’s disease (PD). [ABSTRACT FROM AUTHOR]

The circadian timing system controls drug metabolism and cellular processes over the 24 h period in every cell. Impaired redox homeostasis is a casual factor for a number of diseases and it is desirable to understand the orchestration of circadian clock under oxidative stress in the model organism,Drosophila melanogaster.This study evaluates the effect of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-induced oxidative stress in fruit fly. The characteristics of temporal rhythms (acrophase, amplitude, and mesor) of glutathione peroxides (GPx), reduced glutathione (GSH)), were markedly declined in rotenone-treated flies when compared to other groups. Treatment of hesperidin to rotenone-treated flies significantly increased the mesor and modified the amplitudes of antioxidants. Further, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin results in normalization of the altered rhythms of these indices plausibly by its cytoprotective and antioxidant effects. Impairment of 24 h rhythms in oxidative stress markers and antioxidants were observed during rotenone treatment and the impairment is severe in circadian clock mutantcrybflies. A reversibility of rhythms was prominent consequent to hesperidin treatment in wild-type flies thancrybflies. These findings revealed a role of circadian clock in redox homeostasis and the use ofDrosophilamodel in screening putative antioxidative phytomedicines earlier to their use in mammalian systems. [ABSTRACT FROM PUBLISHER]

Objectives:Parkinson disease (PD) is a neurodegenerative disorder affecting mainly the motor system, as a result of death of dopaminergic neurons in the substantia nigra pars compacta. The present scenario of research in PD is directed to identify novel molecules that can be administered individually or co-administered with L-Dopa to prevent the L-Dopa-Induced Dyskinesia (LID) like states that arise during chronic L-Dopa administration. Hence, in this study, we investigated whetherMorinda citrifoliahas therapeutic effects in rotenone-induced Parkinson’s disease (PD) with special reference to mitochondrial dysfunction mediated intrinsic apoptosis. Methods:Male Sprague-Dawley rats were stereotaxically infused with rotenone (3 µg in both SNPc and VTA) and co-treated with the ethyl acetate extract ofMorinda citrifoliaand levodopa. Results:The results revealed that rotenone-induced cell death was reduced by MCE treatment as measured by decline in the levels of pro-apoptotic proteins. Moreover, MCE treatment significantly augmented the levels of anti-apoptotic Bcl2 and blocks the release of cytochrome c, thereby alleviating the rotenone-induced dopaminergic neuronal loss, as evidenced by tyrosine hydroxylase (TH) immunostaining in the striatum. Discussion:Taken together, the results suggest thatMorinda citrifoliamay be beneficial for the treatment of neurodegenerative diseases like PD. [ABSTRACT FROM AUTHOR]

Previous studies have examined rotenone toxicity on the human central nervous system, especially in the pathogenesis of Parkinson’s disease, but few have investigated the effects of rotenone on the kidney. Here, rotenone-induced nephrotoxicity was evaluated by determining morphological, biochemical, oxidative stress-related, and apoptotic factor alterations in rat renal tissue. Morphological and biochemical analyzes showed that rotenone administration to rats damaged renal tissue. Western blot results revealed that rotenone-induced oxidative damage, causing overproduction of glutathione, malonaldehyde, and reactive oxygen species (ROS), and inhibiting superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Rotenone also decreased the mitochondrial membrane potential and increased voltage-dependent anion channel (VDAC), caspase-3, and caspase-9 protein levels, indicating an association of apoptosis with renal damage. Our results suggest that glutathione, malonaldehyde, and ROS may be signals of rotenone-induced oxidative damage, and that the mitochondrial pathway plays a key role in apoptosis of renal cells following rotenone administration. [ABSTRACT FROM AUTHOR]

The study was designed to evaluate the protective effect of α-mangostin and explore its mechanism in anin vitromodel of Parkinson’s disease (PD) induced by rotenone. SH-SY5Y cells were treated with rotenone and α-mangostin for 24 h. α-Mangostin significantly and concentration-dependently inhibited rotenone-induced cytotoxicity. The rotenone-induced aggregation of α-synuclein and loss of TH were alleviated by α-mangostin. α-Mangostin treatment also reversed the rotenone-induced overproduction of reactive oxygen species, activation of caspases (−8 and −3) and mitochondrial dysfunction, reflected by decrease in mitochondrial membrane potential and cellular ATP levels. These findings suggest that α-mangostin has neuroprotective effects against PD-related neuronal injury. [ABSTRACT FROM PUBLISHER]

Purpose:To assess the radiosensitizing effect of the biguanide drug metformin used alone or in combination with reactive oxygen species (ROS) modifying agentsN-acetyl-L-cysteine (NAC) or emodin, and contrasted to the mitochondrial complex 1 inhibitor rotenone in altering the radiation responses of the p53 wild-type SA-NH and p53 mutant FSa mouse tumor lines grown either in vitro or in vivo. Materials and methods:Tumor cells were grown to confluence in vitro and exposed to a single 4 Gy dose in the presence or absence of metformin (5 mM) and ROS modifiers or to 10 Gy with or without metformin as tumors in the flanks of C3H mice using a tumor growth delay assay. Results:Both metformin and rotenone protected SA-NH (p < .001) while sensitizing FSa (p < .001) to 4 Gy. Neither NAC nor emodin altered metformin’s action. Metformin was also directly toxic to FSa cells (p = .002). In contrast, in vivo metformin (250 mg/kg) sensitized both SA-NH (9-day growth delay,p < .05) and FSa (4-day growth delay,p < .05) tumors if administered 1 h before irradiation. Conclusion:Metformin effects on tumor cells measured under in vitro conditions may differ from those determined in vivo due to p53 and heterogeneous environmental factors. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic neurodegenerative disease, manifested due to the loss of dopaminergic neurons, which ultimately leads to impaired movement in elderly populations. The pathogenesis of PD is associated with numerous factors including oxidative stress, mitochondrial dysfunction and apoptosis. There is no effective therapy available to cure or halt the progression of this disease still now. Asiatic acid (AA) is a triterpene extracted from Centella asiatica has been reported as an antioxidant and anti-inflammatory agent, that offers neuroprotection against glutamate toxicity. Therefore, in this study, we have investigated the effect of AA in a rotenone (an inhibitor of mitochondrial complex I) induced in vitro model of PD. Following the exposure of SH-SY5Y cells to rotenone, there was a marked overproduction of ROS, mitochondrial dysfunction (as indexed by the decrease in mitochondrial membrane potential) and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic and anti-apoptotic indices). Pre-treatment with AA reversed these changes might be due to its antioxidant, mitoprotective and anti-apoptotic properties. However further extensive studies on in vivo models of PD are warranted to prove AA neuroprotective effect before entering into the clinical trial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Brown trout (Salmo trutta) are known to have effects on multiple trophic levels in New Zealand streams, but their impacts on lower trophic levels are less well understood within lentic systems. We examined the effects of brown trout removal using rotenone on zooplankton and phytoplankton community composition in the Upper Karori Reservoir, New Zealand. Significant shifts were observed in zooplankton and phytoplankton composition following removal of brown trout from the reservoir. Shifts in zooplankton community composition did not occur immediately following trout removal (February), but instead followed the likely timing of galaxiid spawning (July). The removal of brown trout likely resulted in reduced predation pressure on galaxiids. A major change occurred in the zooplankton community with the dominance shifting from larger crustaceans to smaller rotifers, indicating an increased predation pressure from the larval native galaxiid. A delayed response in zooplankton community composition change indicates rotenone was not the direct cause of this. A major shift in phytoplankton community composition occurred immediately following trout removal. This was not consistent with the trophic cascade hypothesis of reduced grazing pressure from larger zooplankton due to increased galaxiid predation as a result of brown trout removal. [ABSTRACT FROM PUBLISHER]

Dysfunction of the autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) was thought to be an important pathogenic mechanism in synuclein pathology and Parkinson's disease (PD). In the present study, we investigated the role of sestrin2 in autophagic degradation of α-synuclein and preservation of cell viability in a rotenone-induced cellular model of PD. We speculated that AMP-activated protein kinase (AMPK) was involved in regulation of autophagy and protection of dopaminergic cells against rotenone toxicity by sestrin2. The results showed that both the mRNA and protein levels of sestrin2 were increased in a TP53-dependent manner in Mes 23.5 cells after treatment with rotenone. Genetic knockdown of sestrin2 compromised the autophagy induction in response to rotenone, while overexpression of sestrin2 increased the basal autophagy activity. Sestrin2 presumably enhanced autophagy in an AMPK-dependent fashion, as sestrin2 overexpression activated AMPK, and genetic knockdown of AMPK abrogated autophagy induction by rotenone. Restoration of AMPK activity by metformin after sestrin2 knockdown recovered the autophagy activity. Sestrin2 overexpression ameliorated α-synuclein accumulation, inhibited caspase 3 activation, and reduced the cytotoxicity of rotenone. These results suggest that sestrin2 upregulation attempts to maintain autophagy activity and suppress rotenone cytotoxicity through activation of AMPK, and that sestrin2 exerts a protective effect on dopaminergic cells. [ABSTRACT FROM AUTHOR]

Exposure to rotenone in vivo results in selective degeneration of dopaminergic neurons and development of neuropathologic features of Parkinson's disease (PD). As rotenone acts as an inhibitor of mitochondrial respiratory complex I, we employed oxidative lipidomics to assess oxidative metabolism of a mitochondria-specific phospholipid, cardiolipin (CL), in substantia nigra (SN) of exposed animals. We found a significant reduction in oxidizable polyunsaturated fatty acid (PUFA)-containing CL molecular species. We further revealed increased contents of mono-oxygenated CL species at late stages of the exposure. Notably, linoleic acid in sn-1 position was the major oxidation substrate yielding its mono-hydroxy- and epoxy-derivatives whereas more readily 'oxidizable' fatty acid residues (arachidonic and docosahexaenoic acids) remained non-oxidized. Elevated levels of PUFA CLs were detected in plasma of rats exposed to rotenone. Characterization of oxidatively modified CL molecular species in SN and detection of PUFA-containing CL species in plasma may contribute to better understanding of the PD pathogenesis and lead to the development of new biomarkers of mitochondrial dysfunction associated with this disease. [ABSTRACT FROM AUTHOR]

Rotenone, a commonly-used piscicide, interferes with the cellular respiration of aquatic vertebrates and invertebrates by preventing the uptake of oxygen. While dose-response relationships have been developed for fish, there are limited comparative data available on aquatic insects that respire either with tracheal gills or with a plastron – a thin layer of air trapped by hairs on the exterior of the body. This study assesses the temperature-dependent toxicity of rotenone to gill-respiring aquatic insects, family Coenagrionidae, and plastron-respiring aquatic insects, family Corixidae, at concentrations that are lethal to Mozambique tilapiaOreochromis mossambicus. Both groups of insects were found to be differentially susceptible to rotenone, with survival decreasing as functions of both increased concentration and temperature. The dose-response relationship of Mozambique tilapia was found to be similar to that of other fishes, with 100% mortality achieved at 0.025 mg l-1at both 20 °C and 28 °C. At this concentration, mortality in gill-respiring insects after 48 h was 10% at 20 °C and 28% at 28 °C, which was higher than that of plastron-respiring insects, being 2% and 7% at the same temperatures. At higher concentrations (0.05–0.10 mg l-1), however, mortality of both gill- (>50%) and plastron-respiring (>10%) insects became substantial. [ABSTRACT FROM PUBLISHER]

The potential collateral effects of eradicating invasive fishes in streams necessitate the monitoring of invertebrate communities during treatment. In an environmental rehabilitation programme, non-native smallmouth bass were removed from the lower reaches of the Rondegat River, Western Cape, South Africa, in 2012 and again in 2013 using the piscicide rotenone. A monitoring programme tracked the ecological response of organisms to these activities using quantitative sampling of macroinvertebrates on stones and the ISO-certified SASS5 rapid bioassessment method for assessing macroinvertebrate community integrity. We recorded a significant decrease in macroinvertebrate densities from the stones-in-current biotope following both rotenone treatments. The average score per taxon (ASPT) declined after the first treatment, indicating a loss of taxa sensitive to diminished water quality, then recovered prior to the second treatment, and subsequently no decline was detected after the lower dose used in the 2013 treatment. The SASS values were too variable to reveal trends. The ASPTs indicated that the community may have been resistant to low dose and resilient to high dose, due to inter-treatment recovery following the 2012 treatment, suggesting that the invertebrate assemblage is resilient to the conservative use of rotenone for localised river rehabilitation when upstream sources of recruitment exist. [ABSTRACT FROM PUBLISHER]

Most endemic freshwater fish species of the Cape Floristic Region are listed as threatened, due mainly to the impacts of invasive alien fish species. The piscicide rotenone has been identified as a potential tool to aid the conservation of indigenous species through the removal of invasive fish. Rotenone was used in the Rondegat River, Cederberg, where smallmouth bassMicropterus dolomieuhad extirpated the indigenous fish. An initial rotenone treatment in March 2012 was followed by another in March 2013. Due to concerns following the first treatment about possible build-up of rotenone between treatment stations, the second treatment included monitoring of rotenone concentrations during the treatment. Measured concentrations were consistently below the selected treatment concentration of 37.5 µg l−1and dropped to below the tested effective piscicidal concentration of 12.5 µg l−1at some sampling points. There was no build-up of rotenone within the treatment zones, but rotenone took longer than expected to clear out of the treatment area. The rotenone was effectively neutralised when the neutralisation station was operational, but was still detectable after neutralisation was terminated. [ABSTRACT FROM AUTHOR]

Pachyrhizus erosus(Fabaceae) is a herb commonly known as ‘yam bean’, which has been cultivated in México since pre-Columbian times for its edible tubers. The seeds are also known for their acaricidal and insecticidal properties due to rotenone and other isoflavonoid contents. Rotenone has exhibited cytotoxic activity against several human tumour cell lines; however, its mechanism of action is still not fully understood. In this study, we determined the cytotoxicity of rotenone isolated fromP. erosusseeds on K562 human leukaemia cells. Rotenone exhibited significant cytotoxic activity (IC50 = 13.05 μM), as determined by the MTT assay. Three other isolated isoflavonoids were not cytotoxic. Rotenone genotoxicity was detected using the comet assay. Rotenone induced cell death, and caspase-3 activation as indicated by TUNEL assay, and immunocytofluorescence. Plasmid nicking assay indicated that rotenone does not interact directly with DNA. [ABSTRACT FROM PUBLISHER]

In February 2012 the Rondegat River, in the Cape Floristic Region, was the first river in South Africa where the piscicide rotenone was used to remove an alien invasive fish, smallmouth bassMicropterus dolomieu. In preparation for this treatment, the sensitivity of smallmouth bass to various concentrations of the rotenone formulation CFT Legumine (5% active rotenone) was evaluated a week prior to treatment using standard toxicity tests to determine the minimum effective dose (MED) that would result in 100% mortality after exposure for 4 h. The MED was 0.0125 mg l-1rotenone. Adverse effects, including erratic swimming, loss of equilibrium and death, occurred in a dose-dependent manner with smaller fish responding faster than larger ones. Standard operating procedures for the use of rotenone recommend treatment at a minimum of twice the calculated MED. Given the uncertainty associated with rotenone losses through hydrolysis and photolysis under field conditions, and the possible occurrence of smallmouth bass more tolerant than those tested, a concentration of twice the recommended treatment dose (0.050 mg l-1rotenone) was finally used to treat the Rondegat River for a duration of 6 h. [ABSTRACT FROM PUBLISHER]

Alien fishes are considered the most serious threat to native headwater stream fishes in South Africa. A 4 km reach of the Rondegat River is the first section of a South African river to be rehabilitated through the attempted removal of alien fish by using the piscicide rotenone. The objectives of the current study were to establish the distribution and relative abundance of native and alien fish prior to treatment, and to assess the immediate impact of the treatment on the fish population. Forty-three sites were sampled using backpack electrofishing, snorkel transects and underwater video analysis. In the invaded lower reaches, nativeLabeobarbus capensiswas detected only at very low densities, while three other native fish species were not detected. Alien fish were not detected above a barrier waterfall 5 km upstream of the river's confluence with a reservoir. The fish density of 97 fish per 100 m2in non-invaded reaches was more than an order of magnitude higher than that of 7 fish per 100 m2in the invaded reach. A total of 470Micropterus dolomieuand 139L. capensiswere removed from a 4 km treatment zone during the rotenone operation. No fish were detected in this area after the rotenone treatment. [ABSTRACT FROM AUTHOR]

The nematode (worm) C. elegans is a leading multicellular animal model to study neuronal-basis of behavior. Worms respond to a wide range of stimuli and exhibit characteristic movement patterns. Here we describe the use of a microfluidics setup to probe neuronal activity that relies on the innate response of C. elegans to swim toward the cathode in the presence of a DC electric field (termed "electrotaxis"). Using this setup, we examined mutants affecting sensory and dopaminergic neurons and found that their electrotactic responses were defective. Such animals moved with reduced speed (35-80% slower than controls) with intermittent pauses, abnormal turning and slower body bends. A similar phenotype was observed in worms treated with neurotoxins 6-OHDA (6- hydroxy dopamine), MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine) and rotenone (20-60% slower). We also found that neurotoxin effects could be suppressed by pre-exposing worms to a known neuroprotective compound acetaminophen. Collectively, these results show that microfluidic electrotaxis can identify alterations in dopamine and amphid neuronal signaling based on swimming responses of C. elegans. Further characterization has revealed that the electrotactic swimming response is highly sensitive and reliable in detecting neuronal abnormalities. Thus, our microfluidics setup could be used to dissect neuronal function and toxin-induced neurodegeneration. Among other applications, the setup promises to facilitate genetic and chemical screenings to identify factors that mediate neuronal signaling and neuroprotection. [ABSTRACT FROM AUTHOR]

The etiology of Parkinson's disease (PD) is attributed to both environmental and genetic factors. The development of PD reportedly involves mitochondrial impairment, oxidative stress, α-synuclein aggregation, dysfunctional protein degradation, glutamate toxicity, calcium overloading, inflammation and loss of neurotrophic factors. Based on a link between mitochondrial dysfunction and pesticide exposure, many laboratories, including ours, have recently developed parkinsonian models by utilization of rotenone, a well-known mitochondrial complex I inhibitor. Rotenone models for PD appear to mimic most clinical features of idiopathic PD and recapitulate the slow and progressive loss of dopaminergic (DA) neurons and the Lewy body formation in the nigral-striatal system. Notably, potential human parkinsonian pathogenetic and pathophysiological mechanisms have been revealed through these models. In this review, we summarized various rotenone-based models for PD and discussed the implied etiology of and treatment for PD [ABSTRACT FROM AUTHOR]