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This article throws light upon the limitations of in vitro cytotoxicity studies which are briefly described below.
Toxicity of a given compound is a complex process as it occurs in vivo. This may result in direct damage to cells, alterations in physiological and biochemical functions, inflammatory changes and other systemic effects, not only at the site of application but also at the other sites.
Some of the important in vitro limitations are briefly described with special reference to systemic responses, metabolism and pharmacokinetics.
1. Tissue and Systemic Responses:
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The cultured cells represent the cells in isolation, and not an integral part of a tissue or an organ. The nature of the in vitro effect is measured by cell survival or by an altered metabolic effect. On the other hand, the in vivo reactions are complicated that may lead to tissue responses (fibrosis, inflammatory reaction) or systemic responses (pyrexia, vascular dilation).
Therefore, the in vitro cytotoxic responses have to be considered carefully. In recent years, some attempts are made to create in vitro organotypic cultures by assembly of different cell types. Even with this approach, it is not possible to observe all the tissue, and systemic responses.
2. Metabolism:
The whole body metabolism is complex and well integrated. Some of the compounds that are toxic in vitro are detoxified by the liver. On the other hand, certain non-toxic or less toxic compounds may be converted to more toxic ones in the liver. For these reasons, it is necessary that the in vitro cells are exposed to the same type of compound that is formed in liver after detoxification.
3. Pharmacokinetics:
When the body is exposed to a drug, there occurs tissue penetration, metabolism, clearance and excretion, constituting an organized pharmacokinetics. It is not possible to stimulate these parameters in the isolated cells. However, use of multicellular tumor spheroids has certain advantages with regard to understanding of drug penetration.
