Cell Culture and Neurotoxicity: Testing Strategies and Evaluation

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This essay delves into the critical field of cell culture and its application in understanding and predicting neurotoxicity. It begins by establishing the fundamental role of cells as the building blocks of life and the significance of cell culture systems, both in vitro and in vivo, for biological research, toxicity screening, and therapeutic applications. The essay focuses on evaluating the effectiveness of different cell culture testing strategies in predicting in vivo neurotoxicity, a crucial area for regulatory applications. It highlights the importance of neurotoxicity testing in identifying potential neurotoxic substances and the central nervous system's vulnerability as a primary target. The discussion encompasses the challenges in comparing neurotoxicology and neurobiology, the use of behavioral assessments, and the Functional Observational Batteries (FOB) methods for evaluating sensorimotor function. Furthermore, the essay examines the screening process, hazard characterization, dose-effect relationships, and the mechanisms of action of chemical agents, including the determination of NOAEL and LOAEL. The essay concludes by summarizing the effectiveness of different testing strategies for in vivo toxicology, emphasizing the significance of FOB methods and behavioral assessments in understanding the impact of neurotoxicity.
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Running head: CELL CULTURE
CELL CULTURE AND NEUROTOXICITY
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1CELL CULTURE AND NEUROTOXICITY
Introduction
Cells are the fundamental units of life, which is a preliminary subject of research in
biological studies. Different models and systems are used for research purposes, which helps the
human population for a better understanding of the physiological processes. These cell culture
systems are significant for screening the compounds with toxicity and therapeutic applications.
Two types of cell culture systems can be found in biological researches such as in vitro and in
vivo. In vivo experiments are done in the body of living organisms. A neurotoxicity is a form of
toxicity utilizing biological, chemical or physical agents or factors that are produced. These
agents are the cause of adverse situations or effects on the central or peripheral nervous system
of mammals. This essay is to analyze or evaluate the effect of testing strategies of different cell
culture systems to predict in vivo neurotoxicity.
Discussion
Many regulatory applications must evaluate major toxicity endpoints and these major
toxicity endpoints are related to neurotoxicity. Neurotoxicity testing is important to recognize
potential neurotoxic substances such as lead, mercury, pesticides, and ethanol [1]. Sometimes
neurotoxicity testing is regarded as a factor for the toxicity of target organs; the central nervous
system (CNS) is one of the main target organ systems. Neurotoxicity affects complex integrative
functions such as motor performance, sensory accuracy, memory and cognitive processes of life.
The impacts of neurotoxicity can be found by in vivo experiments or methods. The susceptibility
of various toxic agents differs in specific species in different degrees of effectiveness. In vivo
methods are applied to various animals such as mice and rats. Behavioral assessments are some
of the effective testing techniques which can be opted for chemically induced functional changes
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2CELL CULTURE AND NEUROTOXICITY
in nervous systems. Scientists find difficulties in comparing neurotoxicology and neurobiology.
Behavioral techniques are involved in the analysis of sensory, motor, autonomic and cognitive
function [2]. Behavioral techniques are involved with chemical exposure and a wide array of
different chemicals. The screening tests are typically done with some selective organisms. The
method does not need to involve numerous instrumentation but routine screening is not
appropriate for the organisms.
Functional Observational Batteries are detected and designed for major neurotoxic
effects. The FOB methods are used for evaluating different aspects of the sensorimotor function
of an organism [3]. FOB tests are essentially clinical examinations that detect the presence or
absence and in some cases the relative degree, of specific neurologic signs. During this method,
many neurologic components overlap and can assess the activities in tested individuals. The
number of chemicals tested for neurotoxic potential increases, many different combinations of
affected functions will emerge.
Screening is one f the most fundamental testing strategies to determine clinical potential
in an individual. The initial stage of the screening procedure is to permit the identification of the
hazards. The second stage of the screening procedure is to the characterization of the
neurotoxicity. The characterization method includes the type of structural or functional damage
produced and the degree and location of neuronal loss. The characterization of hazards can be
used in the second stage of screening and analysis of the relationship between the exposure of
neurotoxins and the dose of target organs are calculated. The relationship between dose and
biological responses is also counted. The final stage of neurotoxicity is to study the mechanism
of action of chemical agents. The structure-activity relationships are motivated by the decisions
characterized by the second tier of testing of neurotoxins. Several issues such as the primary
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3CELL CULTURE AND NEUROTOXICITY
target of the nervous system and dose-effect and effect of time can be regarded as sensitive at
some points. The no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect
level (LOAEL) is determined from the screening test of neurotoxicological elements in the
mammals [4]. The mechanisms and actions which are related to the neurobehavioral and
neurochemical state, are responsible for measuring the frequencies of physiological processes.
To find the neurotoxicity in an organism biological markers are used in the new tests and
epidemiological studies.
Conclusion
This essay concludes how different testing strategies are effective for the in vivo
toxicology. Sometimes neurotoxicity testing is regarded as a factor for the toxicity of target
organs. The essay has also found that the susceptibility of various toxic agents differs in specific
species in different degrees of effectiveness. In vivo methods are applied to various animals such
as mice and rats. The FOB methods and behavioral assessments are used for evaluating different
aspects of the sensori-motor function of an organism.
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References
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On the role of DT-diaphorase inhibition in aminochrome-induced neurotoxicity in vivo.
Neurotoxicity research. 2017 Jul 1;32(1):134-40.
2. Fakhri S, Dargahi L, Abbaszadeh F, Jorjani M. Effects of astaxanthin on sensorymotor
function in a compression model of spinal cord injury: Involvement of ERK and AKT signalling
pathway. European Journal of Pain. 2019 Apr;23(4):750-64.
3. Vorhees CV, Sprowles JN, Regan SL, Williams MT. A better approach to in vivo
developmental neurotoxicity assessment: alignment of rodent testing with effects seen in
children after neurotoxic exposures. Toxicology and applied pharmacology. 2018 Sep 1;354:176-
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4. Spittle B. The effect of the fluoride ion on reproductive parameters and an estimate of the safe
daily dose of fluoride to prevent female infertility and miscarriage, and foetal neurotoxicity.
Fluoride. 2017 Jul 1;50(3):287-91.
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