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1.
J Biochem Mol Toxicol ; 35(5): e22741, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33592137

RESUMO

The present study examined the influence of selenium on ciprofloxacin-mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co-treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacin-treated in rats. Selenium treatment also mitigated ciprofloxacin-mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.


Assuntos
Ciprofloxacina/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Reprodução/efeitos dos fármacos , Selênio/efeitos adversos , Testículo/metabolismo , Animais , Sistema Hipotálamo-Hipofisário/patologia , Masculino , Ratos , Ratos Wistar , Selênio/farmacologia , Testículo/patologia
2.
Environ Toxicol ; 36(1): 67-76, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856799

RESUMO

The increase in the exposure to carbon nanotubes (CNTs) and their incorporation into industrial, electronic, and biomedical products have required several scientific investigations into the toxicity associated with CNTs. Studies have shown that the metabolism and clearance of multiwalled CNTs (MWCNTs) from the body involve biotransformation in the liver and its excretion via the kidney. Since oxidative stress and inflammation underlines the toxicity of MWCNT, we investigated the ameliorative effect of kolaviron (KV), a natural antioxidant and anti-inflammatory agent, on hepatorenal damage in rats. Exposure to MWCNTs for 15 days significantly increased serum activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase thereby suggesting hepatic dysfunction. Kidney function, which was monitored by urea and creatinine levels, was also impaired by MWCNTs. Additionally, MWCNTs markedly increased myeloperoxidase activity, nitric oxide level, reactive oxygen and nitrogen species, and tumor necrosis factor level in both tissues. However, KV in a dose-dependent manner markedly attenuated MWCNT-induced markers of hepatorenal function in the serum and MWCNT-associated inflammation in the liver and kidney. Also, MWCNTs elicited significant inhibition of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities. There was a significant diminution in glutathione level (GSH) and enhanced production of malondialdehyde (MDA) in MWCNTs-exposed rats. KV treatment was able to significantly increase the antioxidant enzymes and enhance the GSH level with a subsequent reduction in the MDA level. Taken together, KV elicited ameliorative effects against hepatorenal damage via its anti-inflammatory and antioxidant properties. Thus, KV could be an important intervention strategy for the hepatorenal damage associated with MWCNTs exposure.

3.
Metab Brain Dis ; 35(6): 933-946, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32430695

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease. Currently, the precise pathogenic detail of PD is not entirely clear and first line therapeutics fail to attenuate the progress of the disease. In this study, we examined the neuroprotective effect of kolaviron, a natural antioxidant and anti-inflammatory biflavonoid from Garcinia kola seed, on behavioural impairment, neurodegeneration, oxidative stress and neuroinflammation in an acute MPTP-induced PD model. Kolaviron mitigated the frequently interrupted MPTP-associated hyperkinesia, inefficient gait, immobility, inability to pay attention to sizable holes on walking path, habitual clockwise rotations characterized with minimal diversion of movements and impaired balance. Also, kolaviron suppressed MPTP-mediated striatal oxidative stress, depletion as well as degeneration of dopaminergic terminals, reduced DJ-1 secretion and upregulated expression of caspase-3. Kolaviron facilitated cytoprotective antioxidant response and prevented MPTP-mediated neuroinflammation by blocking striatal infiltration of peripheral CD45R positive cells. Additionally, kolaviron reversed MPTP-induced inhibition of acetylcholinesterase activity. Together, our study provides evidence that the neuroprotective capacity of kolaviron to modulate striatal degeneration, behavioural impairment, antioxidant/redox imbalance and neuroinflammation implicated in the pathogenesis of PD may involve upregulation of DJ-1 secretion and inhibition of CD45R cells infiltration. Our data recommend kolaviron as a possible neuroprotective strategy in the management of Parkinson's disease and the associated behavioural complications, albeit the identity of MPTP-associated striatal CD45R infiltrate needs to be further characterized.


Assuntos
Corpo Estriado/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Flavonoides/uso terapêutico , Antígenos Comuns de Leucócito/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Proteína Desglicase DJ-1 , Animais , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/metabolismo , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Antígenos Comuns de Leucócito/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/fisiologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteína Desglicase DJ-1/metabolismo
4.
Biochem Biophys Res Commun ; 503(1): 171-176, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-29859936

RESUMO

Exposure to pesticide chlorpyrifos (CPF) has been implicated in reproductive deficits in both humans and animals. Diphenyl diselenide (DPDS) is an organoselenium compound widely reported to elicit potent pharmacological activities in several chemically-induced toxicity and disease models. However, there is paucity of scientific information on the influence of DPDS on CPF-induced reproductive dysfunction. The present study investigated the influence of DPDS on CPF-induced functional changes along the hypothalamic-pituitary- testicular axis in rats. CPF was administered alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Results showed that DPDS co-treatment significantly (p < 0.05) abrogated CPF-induced oxidative stress by increasing the antioxidant enzymes activities and glutathione content, decreasing the hydrogen peroxide and lipid peroxidation levels in the hypothalamus, testes and epididymis of the treated rats. Moreover, DPDS co-treatment significantly ameliorated CPF-induced histological alterations in the hypothalamus, testes and epididymis of the treated rats. Besides, the significant augmentation of luteinizing hormone, follicle-stimulating hormone and testosterone levels as well as the testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by DPDS was accompanied by an increase in sperm quality and quantity in the treated rats. Taken together, DPDS abrogates CPF mediated toxicity along the hypothalamic-pituitary-testicular axis in rats via inhibition of lipid peroxidation, enhancement of antioxidant enzymes activities and testicular function. Thus, DPDS may be a possible chemoprotective drug candidate against CPF-induced male reproductive deficits in humans.


Assuntos
Derivados de Benzeno/farmacologia , Clorpirifos/antagonistas & inibidores , Clorpirifos/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Testículo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Epididimo/patologia , Hormônio Foliculoestimulante/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Inseticidas/antagonistas & inibidores , Inseticidas/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue
5.
Biochem Biophys Res Commun ; 503(4): 3167-3173, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30149914

RESUMO

The investigation into the potential health risks associated with the use of engineered nanoparticles is a major scientific interest in recent years. The present study elucidated the involvement of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in carboxylated multi-walled carbon nanotubes (MWCNTs)-induced hepatotoxicity. Pubertal rats were exposed to purified MWCNTs at 0, 0.25, 0.50, 0.75 and 1.0 mg/kg for 5 consecutive days. Results indicated that exposure to MWCNTs caused liver damage evidenced by significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) when compared with control. Moreover, MWCNTs significantly decreased superoxide dismutase (SOD) and glutathione S-transferase (GST) activities as well as glutathione level whereas it significantly increased catalase (CAT) and glutathione peroxidase (GPx) activities in liver of the treated rats. Moreover, the dose-dependent increase in hepatic hydrogen peroxide (H2O2) and lipid peroxidation levels were accompanied by marked increase in micronucleated polychromatic erythrocytes (MNPCE) in the MWCNTs-treated rats. Administration of MWCNTs significantly increased serum concentrations of pro-inflammatory cytokines namely interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the treated rats. Immunohistochemical analysis showed significantly increased COX-2 and iNOS protein expressions in the liver of MWCNTs-treated rats. In conclusion, carboxylated MWCNTs induces hepatic damage via disruption of antioxidant defense systems, promotion of pro-inflammatory cytokines generation and expression of COX-2 and i-NOS in rats.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocinas/imunologia , Fígado/efeitos dos fármacos , Nanotubos de Carbono/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/imunologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Nanotubos de Carbono/química , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/imunologia , Ratos Wistar
6.
Arch Environ Contam Toxicol ; 68(1): 74-82, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25179371

RESUMO

Improper management of hazardous wastes adversely impacts the environment and the public health. The present study was aimed at investigating the influence of Olushosun municipal landfill leachate (OMLL) from Ojota in the Lagos State of Nigeria on testicular function by assessing the plasma concentrations of reproductive hormones, testicular biometal levels, and antioxidant levels as well as observing the histological alterations in testes and epididymides of rats after exposure to 0, 12.5, and 25% OMLL in drinking water for 7 days. Exposure to OMLL significantly decreased the daily fluid intake, but it resulted in testicular biometal accumulation as follows: lead > cadmium > nickel > iron > copper. Acute exposure to OMLL induced oxidative stress and increased the activities of marker enzymes of testicular function but markedly decreased the circulatory concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, thyroid-stimulating hormone, triiodothyronine, and thyroxine. Testicular and epididymal degeneration with significant decrease in sperm quality and quantity were observed in OMLL-exposed rats. Collectively, the data presented herein indicate that exposure to OMLL-induced testicular dysfunction associated with biometal accumulation and endocrine disruption in rats. If the effects can be extrapolated to humans, OMLL may present significant health implications for individuals exposed to OMLL-contaminated substances.


Assuntos
Disruptores Endócrinos/análise , Metais/análise , Poluentes Químicos da Água/análise , Animais , Disruptores Endócrinos/metabolismo , Disruptores Endócrinos/toxicidade , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Metais/metabolismo , Metais/toxicidade , Nigéria , Estresse Oxidativo , Ratos , Testículo/efeitos dos fármacos , Testosterona/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Pharm Biol ; 53(5): 695-704, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25243878

RESUMO

CONTEXT: In Africa, Garcinia kola Heckel (Guttiferae) seed is commonly recommended in folklore medicine for the treatment of diabetes and its associated complications. OBJECTIVE: The present study evaluated this traditional claim by mechanistic investigation into the effect of G. kola seed administration on renal, hepatic, and testicular oxidative damage in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Diabetes mellitus was induced in adult male Wistar rats by an intraperitoneal injection of STZ (50 mg/kg). The diabetic rats were thereafter treated orally once per day with G. kola seed (250 mg/kg) and monitored for 14 d. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress indices, sperm characteristics, and histopathological examination of the kidney, liver, and testes were evaluated to monitor treatment-related effects of G. kola seed in STZ-induced diabetic rats. RESULTS AND DISCUSSION: Garcinia kola seed administration significantly ameliorated hyperglycemia mediated damage by decreasing the blood glucose level (72.8% and 84.6% on the 7th and 14th post-treatment days, respectively), enhancement of the antioxidant system, inhibition of lipid peroxidation, and improving the architecture of the kidney, liver, and testes in STZ-induced diabetic rats. In addition, G. kola seed intervention restored the kidney and liver function biomarkers, the sperm characteristics as well as the plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, triiodothyronine (T3), and thyroxine (T4) to normal in STZ-induced diabetic rats. CONCLUSION: The findings from this investigation provide persuasive scientific support for the traditional use of G. kola seed in the treatment of diabetes and its associated complications.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Garcinia kola , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sementes , Testículo/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Fígado/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Testículo/metabolismo
8.
Food Chem Toxicol ; 178: 113934, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37423315

RESUMO

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.


Assuntos
Gliose , Síndromes Neurotóxicas , Ratos , Masculino , Animais , Ratos Wistar , Gliose/induzido quimicamente , Estresse Oxidativo , Síndromes Neurotóxicas/etiologia , Vitamina E , Furanos/toxicidade
9.
Trends Pharmacol Sci ; 43(8): 669-685, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35031144

RESUMO

Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system. Mechanistically implicated in numerous neurological pathologies, microglia emerge as strong contenders for novel neurotherapies. Shifting away from merely an attenuation of excessive microglial inflammatory and phagocytic activities, current therapies aim toward targeting the complex context-dependent microglial heterogeneity, unveiled by large-scale genetic studies and emerging single-cell analyses. Although lacking the necessary selectivity, initial therapies attempting to target specific state-associated microglial properties and functions (e.g., inflammatory activity, phagocytosis, proliferation, metabolism, or surveillance) are currently under pre- or even clinical (Phase I-IV) investigation. Here, we provide an update on current microglial therapeutic research and discuss what the future in the field might look like.


Assuntos
Sistemas de Liberação de Medicamentos , Microglia , Encéfalo/metabolismo , Humanos , Fagocitose/fisiologia
10.
Sci Rep ; 12(1): 3922, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273283

RESUMO

Loss-of-function mutations in parkin is associated with onset of juvenile Parkinson's disease (PD). Resveratrol is a polyphenolic stilbene with neuroprotective activity. Here, we evaluated the rescue action of resveratrol in parkin mutant D. melanogaster. The control flies (w1118) received diet-containing 2% ethanol (vehicle), while the PD flies received diets-containing resveratrol (15, 30 and 60 mg/kg diet) for 21 days to assess survival rate. Consequently, similar treatments were carried out for 10 days to evaluate locomotor activity, oxidative stress and antioxidant markers. We also determined mRNA levels of Superoxide dismutase 1 (Sod1, an antioxidant gene) and ple, which encodes tyrosine hydroxylase, the rate-limiting step in dopamine synthesis. Our data showed that resveratrol improved survival rate and climbing activity of PD flies compared to untreated PD flies. Additionally, resveratrol protected against decreased activities of acetylcholinesterase and catalase and levels of non-protein thiols and total thiols displayed by PD flies. Moreover, resveratrol mitigated against parkin mutant-induced accumulations of hydrogen peroxide, nitric oxide and malondialdehyde. Resveratrol attenuated downregulation of ple and Sod1 and reduction in mitochondrial fluorescence intensity displayed by PD flies. Overall, resveratrol alleviated oxidative stress and locomotor deficit associated with parkin loss-of-function mutation and therefore might be useful for the management of PD.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Estresse Oxidativo , Resveratrol/farmacologia , Compostos de Sulfidrila , Superóxido Dismutase-1 , Ubiquitina-Proteína Ligases/genética
11.
Biol Open ; 11(11)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326097

RESUMO

Neural stem cells (NSCs) are immature progenitor cells that are found in developing and adult brains that have the potential of dividing actively and renewing themselves, with a complex form of gene expression. The generation of new brain cells in adult individuals was initially considered impossible, however, the landmark discovery of human neural stem cells in the hippocampus has been followed by further discoveries in other discreet regions of the brain. Investigation into the current state in Africa of the research and use of NSCs shows relatively limited activities on the continent. Information on the African application of NSCs for modelling disease mechanisms, drug discovery, and therapeutics is still limited. The International Brain Research Organization (IBRO)-African Regional Committee (ARC), with support from the Company of Biologists, and the Movement Disorder Society, sponsored the first African Basic School on NSC in Ibadan, Nigeria, with the vision of bringing together young neuroscientists and physicians across different fields in neuroscience to learn from leaders who have applied NSCs in stem cell research, the pathophysiology of neurodegenerative diseases, neuroanatomy, and neurotherapeutics. Twenty early-career researchers in academic institutions at junior and senior faculty cadres were selected from South Africa, Uganda and Nigeria. The students and organizer of the school, who wrote this review on the state of NSCs research in Africa, recommended the following: (1) other African countries can take a cue from South Africa and Nigeria in probing the phenomena of adult neurogenesis in unique animal species on the continent; (2) Africa should leverage the expertise and facilities of South African scientists and international collaborators in scaling up NSC research into these unique species and (3) Centers of Excellence should be established on the continent to serve as research hubs for training postgraduate students, and facilities for African scientists who trained overseas on NSCs.


Assuntos
Células-Tronco Neurais , Pesquisa com Células-Tronco , Animais , Adulto , Humanos , Nigéria , Neurogênese/genética , Hipocampo/metabolismo
12.
Front Cell Neurosci ; 15: 670298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211370

RESUMO

Since December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson's disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.

13.
Chemosphere ; 264(Pt 1): 128449, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33032224

RESUMO

The continuous detection of human pharmaceuticals during environmental biomonitoring is a global concern because of the menaces they may exert on non-target organisms. Carbamazepine (CBZ) and diazepam (DZP) are commonly prescribed psychotropic drugs which have been reported to coexist in the environment globally. Nauphoeta cinerea is a common insect with high ecological impact. This study elucidated the influence of co-exposure to DZP (0.5 and 1.0 µg kg-1 diet) and CBZ (1.5 and 3.0 µg kg-1 diet) for 42 days on the behavior and biochemical responses in Nauphoeta cinerea. Results showed that DZP alone did not induce adverse effect on the behavior and antioxidant status in the exposed insects. However, exposure to CBZ alone and binary mixtures of DZP and CBZ significantly decreased locomotor and exploratory accomplishments evidenced by decreased mobile episodes, total mobile time, maximum speed, total distance traveled, absolute turn angle, body rotation and path efficiency in comparison with control. The decline observed in the exploratory activities of insects fed with CBZ alone and the mixtures was confirmed by track plots and heat maps. Further, acetylcholinesterase and antioxidant enzyme activities decreased significantly whereas reactive oxygen and nitrogen species, nitric oxide and lipid peroxidation levels increased significantly in the hemolymph, head and midgut of insects exposed to CBZ alone and the mixtures. Collectively, CBZ alone and binary mixtures of CBZ and DZP caused neurotoxicity via induction of inflammatory and oxidative stress in insects. Nauphoeta cinerea may be a potential non-target insect model for monitoring ecotoxicological hazard of pharmaceuticals.


Assuntos
Diazepam , Poluentes Químicos da Água , Animais , Carbamazepina/toxicidade , Baratas , Diazepam/toxicidade , Humanos , Peroxidação de Lipídeos , Psicotrópicos , Poluentes Químicos da Água/toxicidade
14.
Environ Pollut ; 265(Pt A): 115053, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806419

RESUMO

Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to the ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate the impact of DCF on insects by assessing the behavior and antioxidant defense response in nymphs of N. cinerea exposed to DCF-contaminated food at 0, 0.5, 1.0 and 2.0 µg kg-1 feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in the head, midgut and hemolymph of the insects. Results indicated that DCF-exposed insects exhibited marked reduction in the maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas the total freezing time was increased compared with the control. The diminution in the exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in the head, midgut and hemolymph of the insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.


Assuntos
Baratas , Diclofenaco , Animais , Antioxidantes , Ecossistema , Peroxidação de Lipídeos
15.
Psychopharmacology (Berl) ; 237(11): 3225-3236, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32651640

RESUMO

The asymptomatic and clinical stages of Parkinson's disease (PD) are associated with comorbid non-motor symptoms including gastrointestinal (GI) dysfunction. Although the neuroprotective and gastroprotective roles of kolaviron (KV) have been reported independently, whether KV-mediated GI-protective capacity could be beneficial in PD is unknown. We therefore investigated the modulatory effects of KV on the loss of dopaminergic neurons, locomotor abnormalities, and ileal oxidative damage when rats are lesioned in the nigrostriatal pathway. KV treatment markedly suppressed the behavioral deficit and apomorphine-induced rotations associated with rotenone lesioning. KV attenuated the loss of nigrostriatal dopaminergic neurons and perturbations in the striatal glucose-regulated protein (GRP78) and X-box binding protein 1 (XBP1) levels. Ileal epithelial injury following stereotaxic rotenone infusion was associated with oxidative stress and marked inhibition of acetylcholine esterase activity and reduced expression of occludin in the crypt and villi. While KV treatment attenuated the redox imbalance in the gut and enhanced occludin immunoreactivity, acetylcholinesterase activity was not affected. Our data demonstrate ileal oxidative damage as a characteristic non-motor gut dysfunction in PD while showing the potential dual efficacy of KV in the attenuation of both neural defects and gut abnormalities associated with PD.


Assuntos
Corpo Estriado/efeitos dos fármacos , Flavonoides/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Transtornos Parkinsonianos/prevenção & controle , Rotenona/toxicidade , Substância Negra/efeitos dos fármacos , Animais , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Flavonoides/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/tratamento farmacológico , Degeneração Neural/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Ratos , Rotenona/administração & dosagem , Técnicas Estereotáxicas , Substância Negra/metabolismo
16.
Environ Toxicol Pharmacol ; 78: 103412, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439558

RESUMO

Although sexual health is affected by Parkinson's disease (PD), the effect on testicular health and/or sperm quality is not well discussed. After 21 days of rotenone lesioning, we observed dopaminergic neuronal degeneration in the substantia nigra and hypothalamus. There were minimal SPACA-1-expressing epididymal spermatozoa with morphological abnormalities, scanty luminal spermatozoa and reduced testicular spermatids and post-meiotic germ cells indicating hypospermatogenesis. Occludin-expressing sertoli cells were dispersed over a wide area indicating compromised blood-testes barrier. Activated caspase-3 expression was intense while immunoreactivity of spermatogenic-enhancing SRY and GADD45 g was weak. Although serum follicle stimulating hormone level was not affected, the lesion was associated with reduced serum testosterone level, testicular oxidative damage and inhibition of acetylcholinesterase activity, even when rotenone was not detected in the testes. Together, dopaminergic lesions may mediate testicular and sperm abnormalities via the brain-hypothalamic-testicular circuit independent of the pituitary, thereby establishing a causal link between Parkinsonism and reproductive dysfunction.


Assuntos
Neurônios Dopaminérgicos/patologia , Doença de Parkinson Secundária/patologia , Substância Negra/patologia , Testículo/patologia , Área Tegmentar Ventral/patologia , Acetilcolinesterase/metabolismo , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Masculino , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Ratos , Rotenona , Espermatozoides/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos
17.
Psychopharmacology (Berl) ; 237(4): 1041, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31984444

RESUMO

After publication of this paper, the authors discovered that the name of the first author, Isaac Adegboyega Adedara, was missing in the proof. Dr. Adedara's intellectual contributions to the present article include conception and design of the study, manuscript writing and approval of the final version of the manuscript.

18.
Psychopharmacology (Berl) ; 237(4): 1027-1040, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31897575

RESUMO

Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochemical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p < 0.05) enhanced the locomotor, motor, and exploratory activities namely total distance traveled, maximum speed, total time mobile, mobile episode, path efficiency, body rotation, absolute turn angle, and negative geotaxis when compared with rats exposed to MWCNTs alone. Further, kolaviron markedly abated the decrease in the acetylcholinesterase activity and antioxidant defense system as well as the increase in oxidative stress and inflammatory biomarkers induced by MWCNT exposure in the cerebrum, cerebellum, and mid-brain of rats. The amelioration of MWCNT-induced neuronal degeneration in the brain structures by kolaviron was verified by histological and morphometrical analyses. Taken together, kolaviron abated MWCNT-induced neurotoxicity via anti-inflammatory and redox regulatory mechanisms.


Assuntos
Anti-Inflamatórios/uso terapêutico , Encéfalo/efeitos dos fármacos , Flavonoides/uso terapêutico , Locomoção/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Encéfalo/patologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Garcinia kola , Locomoção/fisiologia , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Sementes
19.
Neurotoxicology ; 73: 132-141, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30930291

RESUMO

Parkinson's disease is the most prevalent movement disorder. Currently, therapies are palliative with associated irreversible behavioural incompetence. Here, we investigated the ability of kolaviron (KV), an anti-inflammatory biflavonoid isolated form Garcinia kola seeds, to rescue striatal neuronal damage and redo-inflammation in rats exposed to rotenone (ROT). Aged rats exposed to 11 days of rotenone intoxication were treated with KV either concurrently or for 18 days. The 18-day regimen included 7 days of pre-treatment prior 11-day concurrent ROT-KV treatment. Rotenone-exposed rats lost weight appreciably and travelled less distance with reduced speed, decline efficiency to maintain a straight path, enhanced freezing, increased immobile episodes and poor hole recognition. The motor incompetence was attributed to enhanced striatal neurodegeneration, increased alpha synuclein formation and reduced tyrosine hydroxylase expression. ROT intoxication significantly increased reactive species production, which co-existed with induction of striatal antioxidant system and damage to biomolecules. ROT additionally upregulated COX-2 expression, enhanced myeloperoxidase activity and increased concentration of striatal inteleukine-6 (IL-6), IL-1ß and tumour necrosis factor (TNF-α). Treatment with kolaviron reversed the rotenone-associated locomotor impairment and exploratory deficits, motor/neuromuscular incompetence, striatal neurodegeneration, neurobiochemical imbalance, altered antioxidant defence system and neuroinflammation. KV-treated rats showed improved capacity to maintain efficient gait with minimal rigidity and enhanced coordination. Taken together, kolaviron exhibited neuroprotective properties, which may be beneficial for the prevention and management of Parkinson's disease, via antioxidant, anti-inflammatory and anti-apoptotic mechanisms.


Assuntos
Anti-Inflamatórios/farmacologia , Antiparkinsonianos/farmacologia , Corpo Estriado/efeitos dos fármacos , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Rotenona , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Corpo Estriado/fisiopatologia , Citocinas/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismo
20.
Biol Trace Elem Res ; 191(1): 135-148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30488170

RESUMO

This study investigated the effects of ethanol (EtOH) on manganese (Mn)-induced striatal toxicity in rat by evaluating the neurobehavioral changes, biochemical and molecular events in rats exposed to Mn alone at 30 mg/kg, or their combination with EtOH at 1.25- and 5-g/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were assessed using a video tracking software (ANY-Maze software) during a 5-min trial in a novel environment. Subsequently, acetylcholinesterase (AChE) activity, oxidative stress markers, histological morphology, and expression of apoptotic proteins (p53 and Bax and caspase-3) and anti-apoptotic protein (Bcl-2) were assessed in the striatum. Results showed that Mn, EtOH, and their combination induced locomotor and motor deficits. Track plot analysis indicated that EtOH exacerbated the Mn-induced reduction in exploratory profiles of exposed rats. Similarly, exposure of rats to Mn, EtOH, or combination of Mn and EtOH resulted in decreased activities of anti-oxidant enzymes, diminished level of reduced glutathione, downregulated Bcl-2 expression, increased AChE activity, enhanced hydrogen peroxide and lipid peroxidation levels, and upregulated expressions of p53, Bax, and caspase-3. Moreover, potentiation of Mn-induced striatal toxicity by EtOH co-exposure was dose dependent. Taken together, it seems that EtOH exacerbates Mn-induced neurobehavioral deficits, oxidative stress, and apoptosis induction via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway in rat striatum.


Assuntos
Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Caspase 3/metabolismo , Corpo Estriado/metabolismo , Etanol/efeitos adversos , Manganês/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Corpo Estriado/patologia , Etanol/farmacologia , Masculino , Ratos , Ratos Wistar
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