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Application of neurotoxin- and pesticide-induced animal models of Parkinson's disease in the evaluation of new drug delivery systems.

Parkinson's disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor sym … use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro tha…

Effect of ebselen on Ca2+ transport in mitochondria.

The seleno-organic compound ebselen mimics the glutathione-dependent, hydroperoxide reducing activity of glutathione peroxidase. The activit … lling or uncoupling is observed. The release of Ca2+ from mitochondria is delayed in the absence of rotenone, i.e. when pyridine nucleotides are maintained in the reduced state due to succinate-driven reversed electron flow. We suggest that ebselen induces Ca2+ release from intact mitochondria via an NAD+ hydrolysis-dependent mechanism.

Detection of barbiturate-induced surface changes in cerebrocortical synaptosomes by phase partitioning in an aqueous two-phase system.

The barbiturates tested in this work (barbital, phenobarbital, thiopental and pentobarbital) modify the partition of synaptosomes in a Dextr … l and barbital showed a higher effect than thiopental and pentobarbital. Dithionite-induced anoxia, rotenone and ouabain also induced a similar increase of partition of synaptosomes into the upper phase, suggesting that the surface changes detected by phase partitioning modification of synaptosomes could be somehow related to the bioenergetic maintenance o …

Effect of uncoupling agents and respiratory inhibitors on the growth of Streptococcus agalactiae.

2,4-Dinitrophenol, dicoumarol, carbonylcyanide, m-chlorophenyl-hydrazone and pentachlorophenol all depressed aerobic molar growth yields of … O(2) consumed per mole of substrate was unchanged, and the respiration was coupled to biosynthesis. Rotenone had no effect on respiration, substrate utilization, or on molar growth yields.

The influence of neuroprotector isatin on haloperidolinduced catalepsy and proteomic profile of mice brain.

Isatin (indol-2,3-dione) is an endogenous regulator found in humans and animals. It interacts with numerous target proteins and exhibits a wide range of biological activities, including neuroprotective action in animal models of Parkinson's disease (PD) induced by administration of neurotoxins MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) or rotenone. An antipsychotic drug haloperidol, which impairs neurotransmitter balance in the nigrostriatal pathway, models dopamine deficiency and promotes the development of motor disorders characteristic of PD. In this work, the effect of two doses …

Enzymatic Synthesis of Anabolic Steroid Glycosides by Glucosyltransferase from Terribacillus sp. PAMC 23288.

The application of steroids has steadily increased thanks to their therapeutic effects. However, alternatives are required due their severe … e, respectively. The viability was higher and cytotoxicity was evident in PC12 cells incubated with rotenone and, testosterone derivatives, compared to the controls. SH-SY5Y cells incubated with H2O2 and nandrolone derivatives remained viable and cytotoxicity was attenuated. Both derivatives enhanced neuronal protective effects and increased the amounts of …

Литиум, иноситол и митохондрия.

Наши недавние исследования ДНК-микроарраев и протеомики в поисках путей, затронутых как хроническим лечением лития, так и вырубкой каждого из двух генов (IMPA1 или Slc5a3) в кодировании белков, связанных с иноситолическим метаболизмом, показали, что регулирование генов, связанных с митохондрией, и протеинов, связанных с автофагией, в передней коре. В отличие от ранее сообщенных наблюдений аберрантной митохондриальной функции у биполярных пациентов, которые оставляют причинно-следственную связь между митохондрической дисфункцией и биполярным расстройством открытым вопросом, поведенческие резуль

Совпадение в аннотации оригинала
Our recent DNA-microarray and proteomics studies searching for pathways affected both by chronic lithium treatment and by knockout of each o … nction and bipolar disorder an open question, the behavioral results of our recent report following rotenone treatment tempt us to speculate that mitochondrial dysfunction predisposes manic behavior and that drugs targeted to ameliorate mitochondrial function are potential preventers of bursting manic episodes. However, the promiscuity of the involvement o …

Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice.

Pathological studies on Parkinson's disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is u…

Characterization of a mitochondrial NADH-dependent nitro reductase from rat brain.

Rat brain mitochondria contain an NADH-linked nitro reductase that converts various aromatic nitro compounds, including the anti-schistosoma … . NAD+ and 4-hydroxymercuribenzoate decrease the enzyme activity. Oxygen, carbon monoxide, cyanide, rotenone, barbiturates, chlorpromazine, dicumarol and chelating agents have no effect on the activity. The subcellular localization, substrate specificity and sensitivity to inhibitors distinguish the mitochondrial nitro reductase from the corresponding micr …

Modulation of microbiota, inflammation, iron status and gene expression of affected receptors in Parkinson's disease rat model by synbiotic and dark chocolate.

Parkinson's disease is among the neurodegenerative diseases that have no promising remedies. The present research is dealing with searching … esignated as synbiotic (Sb). Four groups of rats were assigned; a normal control (C), a group given rotenone to induce Parkinson's disease (P), and two test groups treated with rotenone; one received synbiotic (PSb) and the other treated by dark chocolate (PCh). Results showed plasma soluble transferrin receptor /log ferritin ratios that elevated in the P …

Evaluation of methods for the determination of mitochondrial respiratory chain enzyme activities in human skeletal muscle samples.

The quantification of mitochondrial enzyme activities in skeletal muscle samples of patients suspected of having mitochondrial myopathies is problematic. Therefore, we have evaluated different methods for the determination of activities cytochrome c oxidase and NADH:CoQ oxidoreductase in human skeletal muscle samples. The measurement of cytochrome c oxidase activity in the presence of 200 microM ferrocytochrome c and the detection of NADH:CoQ oxidoreductase as rotenone-sensitive NADH:CoQ(1) reductase resulted in comparable citrate synthase-normalized respiratory chain enzyme activities of both…

Increased lung cell susceptibility to injury due to autophagic overload after exposure to nanoparticles.

Autophagy is an intracellular process that helps maintain cellular homeostasis. In this study, we measured autophagic flux and cellular injury in alveolar epithelial cells (AECs) and lung adenocarcinoma (A549) cells exposed to polystyrene nanoparticles (PNPs: 20 nm, carboxylated, near-infrared dye-labeled) and a secondary insult to explore the effects of limited autophagic capacity. Rat AEC monolayers (RAECMs) and A549 cells were exposed for 24 h to 1) PNP, 2) rotenone (RT: inhibits mitochondrial respiratory chain complex I) or tunicamycin (TN: disrupts protein synthesis and induces the unfold…

Antivirals against monkeypox infections.

UNLABELLED: Monkeypox virus (MPXV) infection in humans are historically restricted to endemic regions in Africa. However, in 2022, an alarmi … nd brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed antiviral activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN- 944, mycophenolate mofetil, and brequinar) and all the compounds from the …

In vivo and in vitro perspectives in Parkinson's disease: Mechanisms and the role of phytomedicine.

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, oxidative stress, neuroinflammation, and α-synuclein aggregation. Despite advances, current treatments only offer symptomatic relief without altering disease progression. This review aims to evaluate the therapeutic potential of plantderived phytochemicals in PD through evidence from both in vivo and in vitro experimental models. Key findings indicate that rodent models (e.g., MPTP, rotenone) and neuronal cell lines (e.g., SH-SY5Y) help replicate PD pathology and mechanistic insights. Phy…

Putative hormetic mechanisms and effects of atypical antipsychotic agents: Implications for study design and clinical psychopharmacotherapeutics.

This paper addresses a novel putative mechanism by which atypical antipsychotic agents induce clinically significant neuroprotective effects that may be viable in the treatment of schizophrenia - and perhaps other neuropsychiatric disorders. Based upon experimental studies with multiple in vitro models (i.e., PC 12 cells, NSC-34 hybrid cells, SH-SY5Y cells, the immune cell line U-937) and several rodent in vivo models, six atypical antipsychotic drugs, within direct experimental comparisons and/or preconditioning protocol studies with six different stressor/toxic agents (i.e. rotenone, hydroge…

Effect of nimodipine on mitochondrial respiration in different rat brain areas after subarachnoid haemorrhage.

The mitochondrial respiration was evaluated in three different rat brain areas (cerebral cortex, hippocampus and brain stem) after experimen … following respiratory parameters were evaluated utilizing glutamate plus malate and succinate plus rotenone as substrates: state 3, state 4, uncoupled state, respiratory control ratio (RCR) and ADP/O ratio. SAH significantly influences respiratory parameters, mainly RCR; the cerebral cortex and brain stem seem to be more sensitive during the acute phase o …

THE EFFECTS OF HYDROCORTISONE ON SYNAPTIC PROCESSES IN PARKINSON'S DISEASE UNDERLYING THE POTENTIAL THERAPEUTIC STRATEGIES.

The study was carried out electrophysiological effects of hydrocortisone for protection on the prelimbic cortex (PrL) neurons in rats, particularly in response to high-frequency stimulation (HFS) of the Caudate-Putamen nuclear complex (CPu) on the models of Parkinson's disease (PD). The study involved 19 rats of the Albino line, each weighing 250 gr. The rats were divided into three experimental groups: intact, rotenone model of Parkinson's disease (PD), and rats with PD but treated with hydrocortisone for protection. Extracellular recording was conducted to measure the impulse activity of sin…