The Neurotoxicity of Organic Solvents, Studied with in Vitro Models

1992 ◽  
Vol 20 (2) ◽  
pp. 290-296
Author(s):  
Hanna Tähti
Keyword(s):  
Organic Solvents ◽  
Cell Membranes ◽  
In Vitro Models ◽  
General Anaesthetic ◽  
Test Models ◽  
Benzene Toluene ◽  
Dose Dependent ◽  
Anaesthetic Action ◽  
Anaesthetic Effect

The present paper deals with the general anaesthetic effect of organic solvents. The emphasis is on cell membranes as models for predicting the adverse reactions of the human nervous system to organic solvents, and for studying the mechanisms of their anaesthetic action. Human and rat erythrocyte and platelet membranes, rat synaptosomal membranes and cultured neural cell membranes were exposed in vitro to various concentrations (3–30mM) of benzene, toluene, o-xylene and styrene in the incubation mixtures. After exposure to a solvent for 30 minutes, the membrane integral protein integrity was determined by measuring ATPase and acetylcholinesterase activities. All measurements were performed in triplicate from 3 or 4 independent experiments with each exposure of solvent and each membrane isolation. The enzyme inhibition was dose-dependent, and differed after solvent treatment in all membrane preparations tested in increasing order, as follows: benzene, toluene, styrene, o-xylene. The results support the protein theories on the mechanism of the anaesthetic action of various industrial organic solvents. The integral membrane proteins contain hydrophobic pockets which may bind anaesthetics, e.g. solvents which change the properties of integral enzymes. The effects of solvents in peripheral models are quite similar to those in neural membranes in vitro. Therefore, these membrane models can serve as test models when the narcotic potencies of the solvents are being evaluated, or at least for screening purposes and for studies of the mechanisms of solvent neurotoxicity.

Hepatoma Cell Cultures as In Vitro Models for the Hepatotoxicity of Xenobiotics

1988 ◽  
Vol 16 (1) ◽  
pp. 32-37
Author(s):  
Margherita Ferro ◽  
Anna Maria Bassi ◽  
Giorgio Nanni
Keyword(s):  
Cell Lines ◽  
Cell Cultures ◽  
Membrane Lipids ◽  
Hepatoma Cell ◽  
Positive Control ◽  
In Vitro Models ◽  
Low Concentrations ◽  
Formation Efficiency ◽  
Dose Dependent

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.

scholarly journals Hypotensive and diuretic activities of aqueous-ethanol extract of Asphodelus tenuifolius

2016 ◽  
Vol 11 (4) ◽  
pp. 830 ◽  
Author(s):  
Naveed Aslam ◽  
Khalid Hussain Janbaz ◽  
Qaiser Jabeen
Keyword(s):  
Aqueous Ethanol ◽  
Urine Volume ◽  
Ethanol Extract ◽  
Antagonistic Activity ◽  
In Vitro Models ◽  
Arterial Blood ◽  
Isolated Aorta ◽  
Dose Dependent

<p class="Abstract">In order to rationalize the traditional uses of <em>Asphodelus </em>tenuifolius in cardiovascular complaints, aqueous-ethanol extract of the plant was investigated for hypotensive and diuretic activities using <em>in vivo</em> and in vitro models. Intravenous administration of the extract in anesthetized rats produced 14.5 (95% CI; 13.3–15.6), 24.5 (95% CI; 21.3-27.9) and 35.3% (95% CI; 32.0–42.5)  fall in mean arterial blood pressure at the doses of 3, 10 and 30 mg/kg, respectively. The extract increased the urine volume and electrolytes excretion significantly at the doses of 300 and 500 mg/kg in rats. In rabbit’s isolated aorta preparations, the extract, like verapamil, relaxed K<sup>+ </sup>(80 mM)-induced contractions more potently than phenylephrine (1 µM)–induced contractions, indicating Ca<sup>2+</sup> antagonistic activity. The extract produced dose-dependent stimulant followed by depressant effects in spontaneously contracting rabbit’s paired atria preparations. The results suggest that the extract of <em>A. </em>tenuifolius has hypotensive and diuretic effects in animals.</p><p> </p>

scholarly journals Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation

Development ◽  
2021 ◽  
Author(s):  
Sophie H. L. Austin ◽  
Rut Gabarró-Solanas ◽  
Piero Rigo ◽  
Oana Paun ◽  
Lachlan Harris ◽  
...  
Keyword(s):  
Stem Cell ◽  
In Vitro Models ◽  
Beta Catenin ◽  
Dependent Manner ◽  
Direct Role ◽  
Adult Nscs ◽  
Hippocampal Networks ◽  
Dose Dependent

Adult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage, but whether it has a direct role in the regulation of NSCs remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of NSCs in an active state and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that deletion of β-catenin in NSCs did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which reconciles some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.

scholarly journals IN VITRO ANTI-INFLAMMATORY ACTIVITY OF 4-BENZYLPIPERIDINE

2016 ◽  
pp. 108 ◽  
Author(s):  
Jayashree V ◽  
Bagyalakshmi S ◽  
Manjula Devi K ◽  
Richard Daniel D
Keyword(s):  
Inhibitory Activity ◽  
Protein Denaturation ◽  
In Vitro Models ◽  
Inflammatory Activity ◽  
Significant Activity ◽  
Standard Drug ◽  
Study Results ◽  
Anti Inflammatory ◽  
Dose Dependent

<p>ABSTRACT<br />Objective: To study the in vitro anti-inflammatory activity of 4-benzylpiperidine.<br />Methods: This study was conducted to evaluate the in vitro anti-inflammatory activity of 4-benzylpiperidine using in vitro models such as inhibition<br />of albumin denaturation and proteinase inhibitory activity.<br />Results: This study revealed the dose-dependent inhibition of protein denaturation and proteinase inhibitory activity by 4-benzylpiperidine.<br />Conclusion: In the present study, results indicate that the 4-benzylpiperidine possess anti-inflammatory properties. The drug inhibited the heat<br />induced albumin denaturation and proteinase inhibitory activity. It shows dose-dependent significant activity when compared with a standard drug.<br />Hence, this study gives an idea that the 4-benzylpiperidine can be used as a lead compound for designing a potent anti-inflammatory drug which can<br />be used to cure inflammation.<br />Keywords: Anti-inflammatory activity, 4-Benzylpiperidine, Protein denaturation, Proteinase inhibitory activity.</p>

scholarly journals The Effect of Oleic and Palmitic Acid on Induction of Steatosis and Cytotoxicity on Rat Hepatocytes in Primary Culture

2015 ◽  
pp. S627-S636 ◽  
Author(s):  
A. MORAVCOVÁ ◽  
Z. ČERVINKOVÁ ◽  
O. KUČERA ◽  
V. MEZERA ◽  
D. RYCHTRMOC ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Functional Capacity ◽  
Rat Hepatocytes ◽  
In Vitro Models ◽  
Albumin Production ◽  
Rat Primary Hepatocytes ◽  
Apoptosis And Necrosis ◽  
Dose Dependent Increase ◽  
Dose Dependent

In vitro models serve as a tool for studies of steatosis. Palmitic and oleic acids can induce steatosis in cultured hepatocytes. The aim of our study was to verify steatogenic and cytotoxic effects of palmitic acid (PA), oleic acid (OA) and their combinations as well as their impact on functional capacity of rat primary hepatocytes. Hepatocytes were exposed to OA or PA (0.125-2 mmol/l) or their combination at ratios of 3:1, 2:1 or 1:1 at the final concentrations of 0.5-1 mmol/l. Both OA and PA caused a dose-dependent increase in triacylglycerol content in hepatocytes. PA was more steatogenic at 0.25 and 0.5 mmol/l while OA at 0.75 and 1 mmol/l. PA exhibited a dose-dependent cytotoxic effect associated with ROS production, present markers of apoptosis and necrosis and a decrease in albumin production. OA induced a damage of the cytoplasmic membrane from 1 mM concentration. Mixture of OA and PA induced lower cytotoxicity with less weakened functional capacity than did PA alone. Extent of steatosis was comparable to that after exposure to OA alone. In conclusion, OA or combination of OA with PA is more suitable for simulation of simple steatosis than PA alone.

The Use of Porcine Proximal Tubular Cells for Studying Nephrotoxicity In Vitro: Validation of the Effects of Culturing and Cryopreservation

1994 ◽  
Vol 22 (6) ◽  
pp. 462-473
Author(s):  
Marieke Kruidering ◽  
Diedka H. Maasdam ◽  
Winfried R. Leeman ◽  
Emile de Heer ◽  
J. Fred Nagelkerke
Keyword(s):  
In Vitro Models ◽  
Halogenated Hydrocarbons ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Extracellular Matrix Components ◽  
Proximal Tubular ◽  
Dose Dependent Decrease ◽  
Controlled Freezing ◽  
Dose Dependent

The susceptibility to nephrotoxins of freshly isolated porcine proximal tubular cells (PPTC) and cultured PPTC in suspension were compared, with a view to using PPTC as in vitro models for studying nephrotoxicity. In a previous paper, we described how, in freshly isolated PPTC, well-known nephrotoxins such as mercury (II) chloride, cisplatin, p-aminophenol and halogenated hydrocarbons caused a dose-dependent decrease in the viability and mitochondrial membrane potential of the PPTC. In this paper, we show that suspensions of cultured PPTC, harvested by trypsinisation, are less susceptible to nephrotoxins, possibly due to the synthesis of extracellular matrix components. PPTC in primary culture are suitable for relatively long-term nephrotoxicity studies. This was demonstrated by incubation with mercury (II) chloride for 24 hours, resulting in a dose-dependent loss of viability. Freshly isolated PPTC can be cryopreserved by computer-controlled freezing. The cryopreserved PPTC displayed an increased susceptibility to mercury (II) chloride and a decreased susceptibility to cisplatin and 1,1-dichloro-2,2-difluoroethylene-cysteine, the toxicity of the latter indicating that the renal enzyme β-lyase remains active during cryopreservation.

scholarly journals Enhanced retinoid response by a combination of the vitamin A ester retinyl propionate with niacinamide and a flavonoid containing Ceratonia siliqua extract in retinoid responsive in vitro models

2020 ◽  
Author(s):  
Eric C.S. Lam ◽  
Rui Li ◽  
MyriamRubecca Rodrigues ◽  
Laura Vires ◽  
Rachel L. Adams ◽  
...  
Keyword(s):  
Vitamin A ◽  
In Vitro Models ◽  
Dependent Manner ◽  
Ceratonia Siliqua ◽  
Promoter Activation ◽  
Fruit Extract ◽  
Photoaged Skin ◽  
Dose Dependent ◽  
Modest Activity

AbstractOBJECTIVESRetinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the Vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containing Ceratonia siliqua (CS) fruit extract in retinoid responsive in vitro models.METHODSRP was tested alone and in combination with Nam and CS in an RARα reporter cell line for promoter activation and compared to trans-retinoic acid (tRA) activation. These treatments were also tested in keratinocytes for gene expression profiling by qPCR using a panel of 40 retinoid responsive genes.RESULTStRA or RP elicited RARα reporter activation in a dose dependent manner. The combination of 0.5 μM or 2 μM RP with 10 mM Nam had a 56% and 95% signal increase compared to RP, respectively. The addition of 1% CS to 0.5 μM or 2 μM RP with 10 mM Nam elicited a further increase of 114% and 156%, respectively, over RP and Nam combinations. All retinoids elicited an increase in expression of 40 retinoid sensitive genes over control levels. Of the 40 genes 27 were enhanced by either 0.5 μM RP or 2 μM RP with 10 mM Nam and 1% CS. Nam or CS had very modest activity in both models.CONCLUSIONThe combination of RP with Nam and CS showed a higher retinoid response than RP in two separate retinoid responsive in vitro models. We hypothesize Nam and CS enhances RP activity by modulating metabolism to tRA via increasing NAD+ pools and inhibiting reduction of retinal (RAL) back to retinol, respectively. The findings provide evidence that this combination may have enhanced efficacy for treating the appearance of photoaged skin.

scholarly journals Investigation of anti-arthritic activity (in-vitro models) of Hibiscus hispidissimus Griffith

2018 ◽  
Vol 7 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Shilpa K ◽  
◽  
Nimmy Chacko ◽  
Prerana Shetty ◽  
Sandhya Savithri A ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Diclofenac Sodium ◽  
In Vitro Models ◽  
Membrane Stabilization ◽  
Reference Drug ◽  
Aerial Parts ◽  
Proteinase Inhibition ◽  
Phytochemical Studies ◽  
Dose Dependent

Aim of the experiment: The present study was designed to investigate the anti-arthritic potential of the plant Hibiscus hispidissimus. Materials and Methods: The aerial parts of the plant was collected, dried and extracted (maceration) with ethanol. Preliminary phytochemical studies were carried out. All the in-vitro models i.e. inhibition of protein denaturation, membrane stabilization and proteinase inhibition were carried out with standard reference drug diclofenac sodium. Result: Dose dependent and significant (p<0.05) anti arthritic activity in in-vitro models were found. Conclusion: The results reveal promising anti arthritic potential of the plant. However further pharmacological investigation using isolated active ingredients can be carried out to confirm its efficacy and mechanism of action

Developing an exposure–dose–response model for the acute neurotoxicity of organic solvents: overview and progress on in vitro models and dosimetry

2005 ◽  
Vol 19 (3) ◽  
pp. 607-614 ◽  
Author(s):  
Philip J. Bushnell ◽  
Timothy J. Shafer ◽  
Ambuja S. Bale ◽  
William K. Boyes ◽  
Jane Ellen Simmons ◽  
...  
Keyword(s):  
Organic Solvents ◽  
Dose Response ◽  
Exposure Dose ◽  
In Vitro Models ◽  
Response Model ◽  
Acute Neurotoxicity
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