Archive for the ‘Reviews’ Category

Review: Mechanisms of lead and manganese neurotoxicity

It has been shown that exposure to high levels of lead and manganese in both children and adults can cause cognitive and behavioural deficits. While both metals having distinct neurological effects, each with different brain targets and modes of action, they do share a key similarity in that they both disrupt synaptic transmission.

In this review Tomas R. Guilarte and April P. Neal summarise the toxicokinetics of lead and manganese; describing their neurotoxic mechanisms and discussing the commonalities in their neurotoxicity.

Mechanisms of lead and manganese neurotoxicity
April P. Neal and Tomas R. Guilarte
DOI: 10.1039/C2TX20064C

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Toxicology Research Review Articles: A Collection

In addition to high quality research papers Toxicology Research features topical review articles across the full range of the journal scope. Since the journal launch and Issue 1  published in July last year, we have aimed at providing readers with strong reviews designed to give an interesting insight into the topic, focussing on the key developments, trends and future directions.

For the benefit of readers we bring together the reviews published so far.
 
We hope you find them interesting and stimulating to read:

Epigenetics – relevance to drug safety science
Catherine C. Priestley, Mark Anderton, Ann T. Doherty, Paul Duffy, Howard R. Mellor, Helen Powell and Ruth Roberts
Toxicol. Res., 2012, 1, 23-31

Mechanisms and modifiers of methylmercury-induced neurotoxicity
Stephanie J. B. Fretham, Samuel Caito, Ebany J. Martinez-Finley and Michael Aschner
Toxicol. Res., 2012, 1, 32-38

Mitochondrial glutathione in toxicology and disease of the kidneys
Lawrence H. Lash
Toxicol. Res., 2012, 1, 39-46

Aminolevulinate dehydratase (δ-ALA-D) as marker protein of intoxication with metals and other pro-oxidant situations
Joao B. T. Rocha, Rogerio A. Saraiva, Solange C. Garcia, Fernanda S. Gravina and Cristina W. Nogueira
Toxicol. Res., 2012, 1, 85-102

Perfluorooctane sulfonate (PFOS) and calcium channel downstream signaling molecules
Yu Wang and Yihe Jin
Toxicol. Res., 2012, 1, 103-107

Role of innate and adaptive immunity during drug-induced liver injury
C. David Williams and Hartmut Jaeschke
Toxicol. Res., 2012, 1, 161-170
 

 S-Methyl-L-cysteine sulphoxide: the Cinderella phytochemical?                                                  William M. B. Edmands, Nigel J. Gooderham, Elaine Holmes and Stephen C. Mitchell
Toxicol. Res., 2013, 2, 11-22

In vitro models for liver toxicity testing                                                                                                                                 Valerie Y. Soldatow, Edward L. LeCluyse, Linda G. Griffith and Ivan Rusyn
Toxicol. Res., 2013, 2, 23-39

Novel in vitro and mathematical models for the prediction of chemical toxicity
Dominic P. Williams, Rebecca Shipley, Marianne J. Ellis, Steve Webb, John Ward, Iain Gardner and Stuart Creton
Toxicol. Res., 2013, 2, 40-59

Fancy writing a review article?  Have a topic in mind that will benefit the community? Send us your suggestions! 
  

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In vitro models for liver toxicity testing

In this review Ivan Rusyn, University of North Carolina, and co-workers present an overview of various traditional and novel liver-derived in vitro systems for hepatotoxicity testing. Examples of such systems include:

  • Primary hepatocytes cultures,
  • Immortalized cell lines,
  • Co-cultures of hepatocytes with liver non-parenchymal cells,
  • Bioartificial livers.

Rusyn et al. discuss the benefits and disadvantages associated with using traditional in vitro systems whilst also examining the usefulness of the novel in vitro liver models for toxicity testing.

Want to know more? Read the entire review for free….

In vitro models for liver toxicity testing
Valerie Y. Soldatow, Edward L. LeCluyse, Linda G. Griffith and Ivan Rusyn
DOI: 10.1039/C2TX20051A

Interested in liver toxicology? You may also be interested in these related articles:

Role of innate and adaptive immunity during drug-induced liver injury

Novel in vitro and mathematical models for the prediction of chemical toxicity

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Role of innate and adaptive immunity during drug-induced liver injury

Drug-induced liver injury (DILI) is a major concern in human health. Idiosyncratic DILI (IDILI) is highly variable in its time to onset and no one clear hypothesis exists to explain the mechanism, although there is a general belief that most cases of IDILI involve some immune mediated component. The most common cause of DILI is acetaminophen (APAP) overdose, and although mechanistically APAP-induced liver injury appears to be fundamentally different from IDILI, there are potential critical events shared between APAP-induced liver injury and IDILI.

In this review C. David Williams and Hartmut Jaeschke, University of Kansas Medical Center:

– Compare the existing hypotheses for potential causes of IDILI and discuss the potential roles of immune involvement in DILI;
– Compare and contrast what is known about the mechanisms of APAP-induced liver injury and IDILI;
– Describe the strategies and methods currently being used to study APAP-induced liver injury.

Read the full review for free or have a browse around the Toxicology Research website to see the latest accepted articles.

Role of innate and adaptive immunity during drug-induced liver injury
C. David Williams and Hartmut Jaeschke
DOI: 10.1039/C2TX20032E

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Novel in vitro and mathematical models for the prediction of chemical toxicity

Current in vitro test systems are poor at predicting the toxicity of chemicals/drugs entering the systemic circulation, particularly to the liver. Such systems fall short for several reasons:
(1) Physiological differences between cells currently used and human hepatocytes in their natural state
(2) Lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity
(3) An inability to assess how low level cell damage may develop into overt organ toxicity in some people
(4) Failure to consider systemic effects.

This review by Dominic P. Williams and colleagues presents an in-depth look at how combining technology, such as bioartificial livers (BALs), and mathematical models can allow the design of in vitro systems that can mimic the in vivo systems more accurately. This would allow the testing of theoretical hypothesis testing and a reduction of in vivo animal testing.

For the complete, detailed discussion read this review for free by following the link below….

Novel in vitro and mathematical models for the prediction of chemical toxicity
Dominic P. Williams, Rebecca Shipley, Marianne J. Ellis, Steve Webb, John Ward, Iain Gardner and Stuart Creton
DOI: 10.1039/C2TX20031G

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S-Methyl-L-cysteine sulphoxide: the Cinderella phytochemical?

This review, from William M. B. Edmands, Nigel J. Gooderham, Elaine Holmes and Stephen C. Mitchell of Imperial College London, summarises the available information regarding the amino acid derivative S-methyl-L-cysteine sulphoxide (SMCSO), which can be found in many vegetables considered beneficial to human health.

Included in the discussion:

  • Its occurrence and distribution
  • Its biosynthesis in plants
  • Its metabolism in mammals and microorganisms
  • Its chemoprotective activity; including its chemoprotective activity, anti-diabetic and cardiovascular effects

Mitchell et al. hope that this review will act as a catalyst to stimulate greater scrutiny of this important amino acid derivative, which they say has surprisingly not received as much as it should have considering its abundance and wide distribution.

Read the full review today for free….. HERE

S-Methyl-L-cysteine sulphoxide: the Cinderella phytochemical?
William M. B. Edmands, Nigel J. Gooderham, Elaine Holmes and Stephen C. Mitchell

Do you have research about S-methyl-L-cysteine sulphoxide? Why not submit it to Toxicology Research today.

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Aminolevulinate dehydratase, more than just a marker of Pb(II)

Aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme that has 3 vicinal thiol/thiolate groups that coordinate with Zn(II) and has been considered a reliable and sensitive marker of Pb(II) exposure.

However, in view of the presence of these vicinal thiol groups in its active centre, δ-ALA-D can also be very sensitive towards being oxidized by different soft electrophiles and by metals that compete with Zn(II) at its active centre.

In this review Joao B. T. Rocha, Cristina W. Nogueira and colleagues from Universidade Federal de Santa Maria, discuss the in vitro and in vivo inhibition of δ-ALA-D by soft electrophiles, such as Hg(II), Cd(II), Sn(II), As(III), Bi(III), In(III), Tl(III), Se(IV) and Te(IV) as well as how δ-ALA-D can be a marker of oxidative stress in human pathologies, such as diabetes and hyperglycemia.

Find out more about how δ-ALA-D is more than a biomarker of Pb(II) but rather a universal marker of oxidative stress by reading the review today… it is free to access after all!

Aminolevulinate dehydratase (δ-ALA-D) as marker protein of intoxication with metals and other pro-oxidant situations
Joao B. T. Rocha, Rogerio A. Saraiva, Solange C. Garcia, Fernanda S. Gravina and Cristina W. Nogueira

Get involved in Toxicology Research

Submit your latest research – there’s still time to be considered for one of the first issues
Sign-up for the contents alerts and newsletter – keep up to date with the latest research published in the journal
• All articles published in 2012 and 2013 are free to access. Arrange for your free access by simply filling in this short online registration form

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Review: Validation and quality control of replacement alternatives – current status and future challenges

Finding alternatives to animal testing is currently a large area of investigation. However, once an alternative method has been developed it must undergo a validation process where it is evaluated for such things as its quality, transferability and predictivity. This means that there can be long delays before the method can be implemented. As such different ways to evaluate a method’s suitability and quality have been proposed.

This review by Marcel Leist, Nina Hasiwa, Mardas Daneshian and Thomas Hartung, discusses the principles of model development and quality control as well as giving an overview on alternative methods to animal testing that have under gone validation. Leist et al. go on to discuss the strengths and weaknesses of current traditional approaches for validation and outline new developments and challenges in the area.

Validation and quality control of replacement alternatives – current status and future challenges
Marcel Leist, Nina Hasiwa, Mardas Daneshian and Thomas Hartung
Toxicol. Res., 2012, Advance Article
DOI: 10.1039/C2TX20011B

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Review: Mitochondrial glutathione in toxicology and disease of the kidneys

This review from Lawrence H. Lash, Wayne State University, summarises the pathways of mitochondrial glutathione transport and discusses studies on its manipulation in toxicological and pathological states. This includes:

  • The biochemistry of glutathione (GSH) in the kidneys
  • The roles of GSH in mitochondrial function
  • The pathways of GSH transport into renal mitochondria
  • Mitochondrial GSH in diabetic nephropathy
  • Mitochondrial GSH in compensatory renal hypertrophy
  • Modulation of mitochondrial GSH transport as a potential therapeutic approach

Read the full review here, and while you are there have a look at the rest our recently published articles.

Mitochondrial glutathione in toxicology and disease of the kidneys
Lawrence H. Lash
Toxicol. Res., 2012, DOI: 10.1039/C2TX20021J

Get involved in Toxicology Research!

  Submit your latest research – there’s still time to be considered for one of the first issues

Sign-up for the contents alerts and newsletter – keep up to date with the latest research published in the journal

• All articles published in 2012 and 2013 are free to access. Arrange for your free access by simply filling in this short online registration form

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