scholarly journals Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology

Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 337
Author(s):  
Teresita Guadalupe López-Aceves ◽  
Elvia Coballase-Urrutia ◽  
Francisco Estrada-Rojo ◽  
América Vanoye-Carlo ◽  
Liliana Carmona-Aparicio ◽  
...  
Keyword(s):  
Cell Damage ◽  
Brain Regions ◽  
Protein Carbonyl ◽  
Histopathological Analysis ◽  
Synthetic Pyrethroids ◽  
Dependent Manner ◽  
Mitochondrial Uncoupling ◽  
Respiratory Parameters ◽  
Species Production ◽  
Dose Dependent

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1β, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

scholarly journals Antioxidant and Anti-Inflammatory Activities of Agrimonia pilosa Ledeb. Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Choon Young Kim ◽  
Qi-Ming Yu ◽  
Hyun-Joo Kong ◽  
Joo-Yeon Lee ◽  
Kyung-Mi Yang ◽  
...  
Keyword(s):  
Cell Damage ◽  
Reducing Power ◽  
Total Phenolic ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Total Antioxidant ◽  
Anti Inflammatory ◽  
Species Production ◽  
Dose Dependent

The purpose of this study is to investigate the effect of Agrimonia pilosa Ledeb. extract (APLE) on lipopolysaccharide- (LPS-) induced cell damage in hepatocytes with a focus on antioxidant and anti-inflammatory activities. Total antioxidant and anti-inflammatory activities of APLE itself were analyzed and phytochemical analysis was performed. Moreover, inhibitory effects of APLE on LPS-induced oxidative stress and inflammation were assessed in human HepG2 hepatocytes. APLE was found to exert α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and nitrite scavenging activities and reducing power in a dose-dependent manner. The total phenolic and flavonoid contents of APLE were 44.30 ± 1.61 mg GAE/g and 29.65 ± 1.81 mg QE/g, respectively. HPLC analysis revealed that gallic acid is the major phenolic compound in APLE, followed by rutin, genistein, taxifolin, quercetin, luteolin, and apigenin, in descending order. Treatment of 100 and 200 μg/mL APLE significantly reduced LPS-stimulated intracellular reactive oxygen species production to the basal level without any cytotoxicity. Oppositely, APLE reversed LPS-suppressed expression of glutathione peroxidase gene and protein. Consistent with this result, APLE suppressed LPS-triggered expression of proinflammatory cytokine genes in a dose-dependent manner. These results reinforce the fact that the antioxidant and anti-inflammatory activity of APLE helps protect hepatocytes from LPS. Thus, APLE may be utilized as a bioactive ingredient in functional foods.

Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

2018 ◽  
Vol 11 (4) ◽  
pp. 4162-4169
Author(s):  
Mayank Kulshreshtha ◽  
Manjul Pratap Singh
Keyword(s):  
Skin Diseases ◽  
Scientific Data ◽  
Water Soluble ◽  
Histopathological Analysis ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Biochemical Studies ◽  
Pharmacological Potential ◽  
Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

scholarly journals Genotoxic and Histopathological Effects of Chlorpyrifos on African Catfish, C. gariepinus and Ameliorative Potentials of Ackee Apple, blighia sapida Seed

2018 ◽  
Vol 6 (1) ◽  
pp. 1 ◽  
Author(s):  
Oluyinka Iyiolai ◽  
A. A. Adeagbo ◽  
W. S. Weliange ◽  
S. I. Abdulkareem ◽  
Anifowoshe T. Abass ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Clarias Gariepinus ◽  
Aquatic Organisms ◽  
Acute Exposure ◽  
Histopathological Analysis ◽  
African Catfish ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Histopathological Effects ◽  
Positive Controls

Chlorpyrifos (CPF) is a very toxic pesticide commonly used for controlling agriculturally important pests. The present study investigates DNA damaging effects of CPF on Clarias gariepinus was assessed using genetic assays. Fish were exposed to varying concentrations of CPF (100ppm, 200ppm and 300ppm) at 96 hours (acute exposure). LC50 of the pesticide was found to be 120ppm and one-tenth of the LC50 (12ppm) was taken for the chronic exposure. Distilled water and colchicine were used as negative and positive controls respectively. After 28 days of chronic exposure, fish were fed with inclusion of B. sapida seed (powder) for 14 days. Liver and gills of the fish were removed following 96h exposure, days 7, 14 and 28 of the chronic exposure as well as after the period of amelioration (14 days) for CA assay and histopathological analysis. The results of CA assay showed statistically significant (p ˂ 0.05) increase in CA in a dose-dependent manner for all the exposed groups after acute exposure and time dependent after chronic exposure. Also, this study showed that CPF can potentially induce genotoxic and histopathological changes in fish and other aquatic organisms.

scholarly journals Ibogaine Modifies GDNF, BDNF and NGF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits

2018 ◽  
Author(s):  
Soledad Marton ◽  
Bruno González ◽  
Sebastián Rodríguez ◽  
Ernesto Miquel ◽  
Laura Martínez Palma ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Acute Administration ◽  
Dependent Manner ◽  
Self Administration ◽  
Seeking Behavior ◽  
A Site ◽  
Dose Dependent

<p>Ibogaine is a psychedelic alkaloid which has been subject of intense scientific research due to its reported ability to attenuate drug-seeking behavior. Recent work suggested that ibogaine effects on alcohol self-administration in rats was related to the release of Glial Cell Derived Neurotrophic Factor (GDNF) in the Ventral Tegmental Area (VTA), a mesencephalic region which hosts soma of dopamine neurons. It is well known that neurotrophic factors (NFs) mediate the neuroadaptations induced in the mesocorticolimbic dopaminergic system by repeated exposure to drugs. Although previous reports have shown ibogaine´s ability to induce GDNF expression in rat midbrain, there are no studies addressing its effect on the expression of GDNF, Brain Derived Neurotrophic Factor (BDNF) or Nerve Growth Factor (NGF) in distinct regions containing dopaminergic neurons. In this work, we examined the effect of ibogaine acute administration on the expression of these NFs in the VTA, Prefrontal Cortex (PFC), Nucleus Accumbens (NAcc) and the Substantia Nigra (SN). Thus, rats were i.p. treated with ibogaine 20 mg/kg (I<sub>20</sub>), 40 mg/kg (I<sub>40</sub>) or vehicle, and NFs expression was analyzed after 3 and 24 hours. Only at 24 h an increase of the expression for the three NFs were observed in a site and dose dependent manner. Results for GDNF showed that only I<sub>40</sub> selectively upregulated its expression in the VTA and SN. Both doses of ibogaine elicited a large increase in the expression of BDNF in the NAcc, SN and PFC, while a significant effect was found in the VTA only for I<sub>40</sub>. Finally, NGF was found to be upregulated in all regions after I<sub>40</sub>, while a selective upregulation was found in PFC and VTA for the I<sub>20</sub> treatment. An increase in the content of mature GDNF was observed in the VTA but no significant increase in the mature BDNF protein content was found in all the studied areas. Interestingly, an increase in the content of proBDNF was detected in the NAcc for both treatments. Further research is needed to understand the neurochemical bases of these changes, and to confirm their contribution to the anti-addictive properties of ibogaine. </p>

scholarly journals RAPHANUS SATIVUS LINN. A NEW ANTINOCICEPTIVE FOR DIABETIC NEUROPATHY IN RATS DETERMINED BY RANDALL SELITTO APPROACH

2019 ◽  
pp. 529-534
Author(s):  
SAMBIT KUMAR SAHOO ◽  
STHITAPRAGNYA PANDA
Keyword(s):  
Sciatic Nerve ◽  
Raphanus Sativus ◽  
Diabetic Control ◽  
Nerve Degeneration ◽  
Control Group ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Hot Plate ◽  
End Of Treatment ◽  
Dose Dependent

Objective: The objective of the study was to evaluate the antinociceptive effect of Raphanus sativus Linn. using Randall Selitto method. Methods: Streptozotocin, lard, casein, cholesterol, DL-methionine, yeast powder, quercetin, thiobarbituric acid, 2-nitrobenzoic acid (5, 5, Dithiobis), hematoxylin, and hydrogen peroxide were used. A diet rich in fat content was fed to the animals for a period of 2 weeks. After a stabilization period of 2weeks, the treatment period started and continued for a period of 8weeks. The nociceptive parameters were assessed once a week by Randall Selitto method and hot plate test. After treatment, the animals were sacrificed, and antioxidant parameters were assessed using sciatic nerve homogenate and histopathological analysis of sciatic nerve. Results: Treatment R. sativus extract (RSE 100 mg/kg and 200 mg/kg) appreciably declined the levels of blood glucose in a dose-dependent manner, and it was comparable with standard quercetin. A significant increase in pain threshold levels was observed by the treatment RSE in hot plate method after the 4th week compared to diabetic control, and it was consistent until the end of treatment (p<0.01, p<0.001). In Randall Selitto method RSE produced a significant increase in paw withdrawal threshold after the 4th week compared to diabetic control, and it was consistently increased until the end of treatment. RSE (100 and 200 mg/kg) significantly restored the levels of antioxidant enzymes and decreased lipid peroxidation in a dose-dependent fashion in comparison with the diabetic control group. RSE (100 mg/kg and 200 mg/kg) attenuated the nerve degeneration and axonal swelling along with quercetin. Conclusion: The findings from the current study showed the antinociceptive and antioxidant effect of R. sativus in neuropathic pain in diabetes.

scholarly journals Cytotoxicity of Voriconazole on Cultured Human Corneal Endothelial Cells

2011 ◽  
Vol 55 (10) ◽  
pp. 4519-4523 ◽  
Author(s):  
Sang Beom Han ◽  
Young Joo Shin ◽  
Joon Young Hyon ◽  
Won Ryang Wee
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Toxic Effect ◽  
Cell Damage ◽  
Morphological Characteristics ◽  
Cell Counting ◽  
Dependent Manner ◽  
Corneal Endothelial Cells ◽  
Human Corneal Endothelial Cells ◽  
Dose Dependent

ABSTRACTThe purpose of the present study was to evaluate the toxicity of voriconazole on cultured human corneal endothelial cells (HCECs). HCECs were cultured and exposed to various concentrations of voriconazole (5.0 to 1,000 μg/ml). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) and live/dead viability/cytotoxicity assays. Cell damage was assessed using phase-contrast microscopy after 24 h of exposure to voriconazole. To analyze the effect of voriconazole on the intercellular barrier, immunolocalization of zonula occludens 1 (ZO1) was performed. A flow cytometric assay was performed to evaluate the apoptotic and necrotic effects of voriconazole on HCECs. Cytotoxicity tests demonstrated the dose-dependent toxic effect of voriconazole on HCECs. Voriconazole concentrations of ≥100 μg/ml led to a significant reduction in cell viability. The morphological characteristics of HCECs also changed in a dose-dependent manner. Increasing concentrations of voriconazole resulted in fading staining for ZO1. Higher concentrations of voriconazole resulted in an increased number of propidium iodide (PI)-positive cells, indicating activation of the proapoptotic pathway. In conclusion, voriconazole may have a dose-dependent toxic effect on cultured HCECs. The results of this study suggest that although voriconazole concentrations of up to 50 μg/ml do not decrease cell viability, intracameral voriconazole concentrations of ≥100 μg/ml may increase the risk of corneal endothelial damage.

High-affinity choline uptake in regions of rat brain and the effect of antidepressants

1979 ◽  
Vol 57 (6) ◽  
pp. 595-599 ◽  
Author(s):  
P. D. Hrdina ◽  
K. Elson
Keyword(s):  
Rat Brain ◽  
Tricyclic Antidepressants ◽  
Brain Regions ◽  
Choline Uptake ◽  
Dependent Manner ◽  
Choline Transport ◽  
High Affinity ◽  
Michaelis Constants ◽  
Dose Dependent ◽  
The Brain

The effect of tricyclic antidepressants, chlorpromazine, and some monoamine oxidase inhibitors on the accumulation of [14C]choline by crude synaptosomal (P2) fraction from different regions of rat brain (cortex, striatum, and hippocampus) was investigated. Analysis of choline uptake kinetics resulted in high- and low-affinity components with different Michaelis constants. All tricyclic antidepressants tested inhibited in a dose-dependent manner the high-affinity choline uptake in the three regions, amitriptyline being the most potent. The IC50 values correlated significantly with the relative potencies of imipramine congeners in binding to muscarinic receptors in the brain. Neither tranylcypromine nor pargyline in concentrations up to 0.1 mM had any effect on choline transport. Concentrations of tricyclic antidepressants effective in inhibiting the uptake of choline failed to influence significantly the activity of choline acetyltransferase in brain regions examined. The results suggest that the effect of imipramine congeners on high-affinity choline uptake may be reflected in the anticholinergic properties of these compounds.

scholarly journals Flucytosine and Amphotericin B Coadministration Induces Dose-Related Renal Injury

Dose-Response ◽  
2017 ◽  
Vol 15 (2) ◽  
pp. 155932581770346 ◽  
Author(s):  
Alexandra Folk ◽  
Cornel Balta ◽  
Hildegard Herman ◽  
Alexandra Ivan ◽  
Oana Maria Boldura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Electron Microscopy ◽  
Amphotericin B ◽  
Nuclear Translocation ◽  
Fungal Infections ◽  
Histopathological Analysis ◽  
High Morbidity ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Tgf Β1

Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner. The immunopositivity of tumor necrosis factor-α and interleukin-6 (IL-6), together with IL-6 gene expression, increased both in tubular and glomerular cells. Amphotericin B–flucytosine cotreatment increased significantly the number of terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end-labeling positive nuclei. Apoptotic cells in renal tubuli were confirmed by electron microscopy. Histopathological analysis revealed collagen accumulation at the glomerular level. Collagen was also evidenced in the glomeruli at the dose of 900 μg/kg AMF+150mg/kg FL by Masson-Goldner trichrome staining and electron microscopy. Moreover, antifungal cotherapy induced upregulation of transforming growth factor beta 1 (TGF-β1) gene expression in a dose-dependent manner. Inflammation and epithelial tubular apoptosis are associated with TGF-β1 activation and initiation of the early stage of glomerular fibrosis at higher doses, leading to tubule–interstitial fibrosis.

scholarly journals Uses of Elaeis guineensis oil for Stress Management during the Transportation of Catfish Fingerlings: A Dose-Dependent Outcome

2021 ◽  
pp. 14-22
Author(s):  
Mengue Ngadena Yolande Sandrine ◽  
Essoh Etouke Adrien ◽  
Tchiedjo Marie Laure ◽  
Sulem Yong Nina Nindum ◽  
Fifen Ngapout Rodrigue ◽  
...  
Keyword(s):  
Stress Management ◽  
Elaeis Guineensis ◽  
Antioxidant Activities ◽  
High Dose ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Antioxidant Power ◽  
Ldh Activity ◽  
Dose Dependent

Cameroonian farmers used Elaeis guineensis oil (EGO) named usually palm oil to reduce stress and mortality during the transportation of catfish fingerlings. The present study is aimed to evaluate the uses of EGO for stress management during the transportation of catfish fingerlings. Antioxidant activities of EGO were assessed in vitro. 1500 fingerlings were transported from Douala (Littoral Region, Cameroon) to Yaoundé (Centre Region Cameroon). The transportation was for 7 h 55 min in black tins of 10 L which contain 8 L of water and 100 fingerlings each. The following treatment was administrated: commercial anti-stress, 2, 4, and 6 drops of EGO. Control received no treatment and all groups were triplicated. After 10 fingerlings were sacrificed by decapitation. Total protein, total bilirubin (TB), triglycerides level, and lactate deshydrogenase (LDH) activity were assessed in the liver as well as oxidant stress parameters. Brain and gills were fixed for histopathological analysis. Results showed that transportation of catfish fingerlings induced a significant increase of TB level and LDH activity in the liver. Indeed, it induced cerebellar and gills necrosis. Moreover, EGO exhibits antioxidant activities in vitro against DPPH, ABTS radicals, and possesses a ferric reducing antioxidant power of 6.31 mEAG/g. This observation was confirmed in vivo by the increase in a dose-dependent manner of GSH and nitrites levels in the liver compared to control. However, the administration of 6 drops of EGO increased significantly (p < 0.05) the activity of LDH in the liver compared to control. Thus, high dose induced anaerobic respiration which was confirmed by alveolar necrosis in gills and neurodegeneration although low dose of EGO (2-4 drops) prevented those alterations compared to control. Hence, low doses of Elaeis guineensis oil can prevent liver, cerebellar and gills impairment during artisanal transportation to reduce the effects of stress.

scholarly journals A Novel Orthotopic Implantation Technique for Osteosarcoma Produces Spontaneous Metastases and Illustrates Dose-Dependent Efficacy of B7-H3-CAR T Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Lindsay Jones Talbot ◽  
Ashley Chabot ◽  
Amy Funk ◽  
Phuong Nguyen ◽  
Jessica Wagner ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Metastatic Disease ◽  
Surgical Removal ◽  
Histopathological Analysis ◽  
Dependent Manner ◽  
Car T Cells ◽  
Post Surgery ◽  
Car T ◽  
Dose Dependent

The outcome for metastatic pediatric osteosarcoma (OS) remains poor. Thus, there is an urgent need to develop novel therapies, and immunotherapy with CAR T cells has the potential to meet this challenge. However, there is a lack of preclinical models that mimic salient features of human disease including reliable development of metastatic disease post orthotopic OS cell injection. To overcome this roadblock, and also enable real-time imaging of metastatic disease, we took advantage of LM7 OS cells expressing firefly luciferase (LM7.ffLuc). LM7.ffLuc were implanted in a collagen mesh into the tibia of mice, and mice reliably developed orthotopic tumors and lung metastases as judged by bioluminescence imaging and histopathological analysis. Intratibial implantation also enabled surgical removal by lower leg amputation and monitoring for metastases development post-surgery. We then used this model to evaluate the antitumor activity of CAR T cells targeting B7-H3, an antigen that is expressed in a broad range of solid tumors including OS. B7-H3-CAR T cells had potent antitumor activity in a dose-dependent manner and inhibited the development of pulmonary metastases resulting in a significant survival advantage. In contrast T cells expressing an inactive B7-H3-CAR had no antitumor activity. Using unmodified LM7 cells also enabled us to demonstrate that B7-H3-CAR T cells traffic to orthotopic tumor sites. Hence, we have developed an orthotopic, spontaneously metastasizing OS model. This model may improve our ability not only to predict the safety and efficacy of current and next generation CAR T cell therapies but also other treatment modalities for metastatic OS.

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